presentation on kidney stones

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Last updated: May 25, 2023 Revisions: 19

• 1.1.1 Location of Ureteric Stones
• 2 Clinical Features
• 3 Differential Diagnosis
• 4.1 Imaging
• 5.1.1 Criteria for Inpatient Admission
• 5.1.2 Stent Insertion or Nephrostomy
• 5.2 Definitive Management
• 6.1 Management of Recurrent Stone Formers
• 7 Bladder Stones
• 8 Key Points

Introduction

Renal tract stones  (also termed urolithiasis) are a common condition, affecting around 2-3% of the Western population. They are  more common in males  and typically affect those <65yrs. They commonly form as renal stones  (within the kidney) but can migrate to become  ureteric stones  (within the ureter).

Around 80% of urinary tract stones are made of calcium , as either calcium oxalate (35%), calcium phosphate (10%), or mixed oxalate and phosphate (35%). The remaining stone compositions include struvite stones* (magnesium ammonium phosphate), urate stones (the only radiolucent stones), and cystine stones (typically associated with familial disorders affecting cystine metabolism).

*Struvite stones are often large soft stones, the most common cause of “staghorn calculi” (Fig. 1), whereby the stone will fill the renal pelvis

Figure 1 – A large staghorn calculi, as seen on plain film abdominal radiograph

Pathophysiology

The basis for formation of urinary tract stones is  over-saturation of urine . Calcium and oxalate precipitate at lower saturation levels and are therefore the most common stone composition.

However, certain stone types that form may also be caused by a specific underlying pathology.

For struvite stones , also called infection stones, form in alkaline urine in the presence of urease-producing organisms, such as Proteus and Klebisella species. Urease catalyses urea into carbon dioxide and ammonia, which leads to the precipitation of magnesium ammonium phosphate crystals .

For urate stones ,  high levels of purine  in the blood, either from diet (e.g. red meats) or through haematological disorders (such as myeloproliferative disease), results in increase of urate formation and subsequent crystallisation in the urine.

For cystine stones , these are typically associated with  homocystinuria , an inherited defect that affects the absorption and transport of cystine in the bowel and kidneys; as citrate is a stone inhibitor, hypocitraturia from the condition can thus predispose affected individuals to recurrent stone formation.

Location of Ureteric Stones

For stones that enter the drainage system of the urinary tract, there are three natural narrowed points where stones are likely to impact:

• Pelviureteric Junction (PUJ), where the renal pelvis becomes the ureter
• Crossing the pelvic brim, where the iliac vessels travel across the ureter in the pelvis
• Vesicoureteric Junction (VUJ), where the ureter enters the bladder

Clinical Features

The most common presenting symptom of ureteric stone is  pain *, termed ureteric/renal colic, which occurs from the increased peristalsis from around the site of obstruction. The pain has a sudden onset , severe, and radiates from  flank to pelvis  (termed “loin to groin”), often associated with nausea and vomiting.

Distal ureteric stones may cause urinary frequency or need to micturate (despite an empty bladder). Haematuria occurs in around 90% cases, however this is typically non-visible. In certain cases, renal calculi can become infected , therefore associated symptoms, such as  rigors, fevers, or lethargy. may be present; in severe cases, patient’s may shown clinical features of sepsis .

Examination is typically unremarkable , occasionally demonstrating some  tenderness in the affected flank . There may be signs of dehydration, from reduced fluid intake secondary to associated vomiting.

*It is possible to have no pain with a stone, especially if the stone is non-obstructing

Figure 2 – Macroscopic appearance of two renal calculi

Differential Diagnosis

Differentials for flank pain include pyelonephritis , ruptured AAA, biliary pathology, bowel obstruction, lower lobe pneumonia, or musculoskeletal related pain.

Investigations

A urine dip can show microscopic haematuria, as well as evidence of infection (always ensure to send a urine culture as well in such cases).

Routine bloods should be performed, include FBC & CRP (for evidence of infection) and U&Es (to assess renal function). Urate and calcium levels can also aid in the assessment of stone analysis; if the patient notices they have passed the stone during micturition, retrieval of the stone and sending for analysis can also be of use.

The gold standard for diagnosis of renal stones is a non-contrast CT scan  of the renal tract (KUB). The benefit of the CT KUB (Fig. 3) as an imaging modality is the high sensitivity and specificity in identifying stone disease, as well as concurrent assessment of any alternative pathology.

Ultrasound scans of the renal tract can often be used concurrently in cases of known stone disease, to assess for any hydronephrosis (they can also often detect renal stones, however not ureteric stones). Its benefits are in no radiation risk, however are often operator dependent.

Plain film abdominal radiographs  (AXR) are rarely used for the initial assessment of stone disease, as not all stones are radio-opaque which limits their use, alongside their associated radiation exposure. However, if a patient is known to have radio-opaque urinary tract calculi an AXR may be used as part of stone surveillance .

Figure 3 – A 3mm ureteric stone on non-contrast CT axial scan

Initial Management

Patients with renal stones will often be dehydrated , secondary to reduced oral fluid intake +/- vomiting, so ensure adequate fluid resuscitation if required.

For the majority of cases, renal stones will  pass spontaneously  without further intervention*, especially if in the distal ureter or <5mm in diameter. Ensuring patients have  sufficient analgesia is paramount (NSAIDs per rectum are the most effective).

Any evidence of significant infection or sepsis present warrants intravenous antibiotic therapy and urgent referral to the urology team.

* Alpha receptor antagonists, such as Tamsulosin, are not routinely used for ureteric stones – there is limited evidence that their use may be beneficial in distal ureteric stones >8mm

Criteria for Inpatient Admission

The majority of renal stones can be treated in the outpatient setting. However, criteria that often warrant the need for hospital admission include:

• Post-obstructive acute kidney injury
• Uncontrollable pain from simple analgesics
• Evidence of an infected stone(s)
• Large stones (>5mm)

Stent Insertion or Nephrostomy

Patients with any evidence of  obstructing stones  may warrant primary ureteroscopy or ESWL (see below) to clear the stone, but if they have any evidence of infection or acute kidney injury , they need urgent decompression with stent insertion or a nephrostomy.

Retrograde stent insertion is the placement of a stent within the ureter, approaching from distal to proximal via cystoscopy (Fig. 4). It allows the ureter to be kept patent and temporarily relieve the obstruction.

A nephrostomy is a tube placed directly into the renal pelvis and collecting system, relieving the obstruction proximally (Fig. 5). If required, an anterograde stent can subsequently be passed via the same tract made.

Figure 4 – AXR showing a JJ stent inserted, with associated right renal stone

Definitive Management

Definitive treatment of retained renal or ureteric stones can be achieved by several methods for stones that do not pass spontaneously.

Extracorporeal Shock Wave Lithotripsy (ESWL) involves targeted sonic waves to break up the stone, to then be passes spontaneously. This is typically reserved for small stones (<2cm), performed via radiological guidance (either X-ray or ultrasound imaging). Contra-indications include pregnancy and those on anticoagluants or coagulopathy

Percutaneous nephrolithotomy (PCNL) is used for renal stones only, being the preferred method for large renal stones (including staghorn calculi). Percutaneous access to the kidney is performed, with a nephroscope passed into the renal pelvis. The stones can then be fragmented using various forms of lithotripsy.

Flexible uretero-renoscopy (URS) involves passing a scope retrograde up into the ureter, allowing stones to be fragmented through laser lithotripsy and the fragments subsequently removed.

Figure 5 – Percutaneous nephrostomy tube placed through a calyx into the lower pole of a kidney with hydronephrosis; the tube in (A) and the curled distal end (the “pigtail”) in (B)

Complications

The main complications that can occur from ureteric stones is infection and post-renal acute kidney injury , however both can be treated if managed early.

Recurrent renal stones can lead to renal scarring and loss of kidney function

Management of Recurrent Stone Formers

Patients who are recurrent stone formers often need specialised management, with the underlying cause identified and managed as appropriate.

All these patients should be advised to stay hydrated. If the patient is unable to retrieve any passed stones, ensure serum urate and calcium levels are checked.

Specific management options depend on the underlying stone composition:

• Oxalate stone formers should be advised to avoid high purine foods and high oxalate foods (such as nuts, rhubarb, and sesame)
• Calcium stone formers should have PTH levels checked to exclude any primary hyperparathyroidism and avoid excess salt in their diet
• Urate stone formers should be advised to avoid high purine foods (such as red meat and shellfish) and may need to be considered for urate-lowering medication (e.g. allopurinol)
• Cystine stone formers may warrant genetic testing for underlying familial disease

Bladder Stones

Bladder stones  typically form from urine stasis within the bladder, hence are commonly seen in cases of  chronic urinary retention . They may also occur secondary to infections (classically schistosomiasis) or as passed ureteric stones, however if they are identified in a male patient, then bladder outflow surgery should be considered.

They will most often present with  lower urinary tract symptoms  and require investigation the same as for renal and ureteric stones. Definitive management is through  cystoscopy , allowing the stones to drain or fragmenting them through lithotripsy if required.

The chronic irritation of the bladder epithelium from a bladder stone can also predispose to the  development of SCC bladder cancer .

• Renal stones are common, with several subtypes of composition possible
• Patients classically present with one-sided colicky flank pain, radiating to the groin
• Gold standard for diagnosis is a non-contrast CT KUB scan
• Most stones will pass naturally with analgesia and hydration, however several management options are available for those that remain

[start-clinical]

[end-clinical]

Distal ureteric stones may cause urinary frequency or need to micturate (despite an empty bladder). Haematuria occurs in around 90% cases, however this is typically non-visible. In certain cases, renal calculi can become infected , therefore associated symptoms, such as  rigors, fevers, or lethargy. may be present; in severe cases, patient's may shown clinical features of sepsis .

* Alpha receptor antagonists, such as Tamsulosin, are not routinely used for ureteric stones - there is limited evidence that their use may be beneficial in distal ureteric stones >8mm

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Nephrolithiasis Clinical Presentation

• Author: Chirag N Dave, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
• Sections Nephrolithiasis
• Practice Essentials
• Pathophysiology
• Epidemiology
• Patient Education
• Physical Examination
• Complications
• Approach Considerations
• Blood Studies
• 24-Hour Urine Profile
• Plain (Flat Plate or KUB) Radiography
• Ultrasonography
• Intravenous Pyelography (Urography)
• Computed Tomography Scanning
• Plain Renal Tomography
• Retrograde Pyelography
• Nuclear Renal Scanning
• Magnetic Resonance Imaging
• Emergency Management of Renal Colic
• Surgical Care
• Medical Therapy for Stone Disease
• Dietary Measures
• Prevention of Nephrolithiasis
• Consultations
• Long-Term Monitoring
• Medication Summary
• Analgesics, Narcotic
• Analgesics, Miscellaneous
• Analgesics, Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
• Calcium Channel Blockers
• Alpha Blockers, Antihypertensives
• Xanthine Oxidase Inhibitors
• Alkalinizing Agents, Oral
• Antiemetics
• Antibiotics
• Questions & Answers
• Media Gallery

Patients with urinary calculi may report pain, infection, or hematuria. Small nonobstructing stones in the kidneys only occasionally cause symptoms. If present, symptoms are usually moderate and easily controlled. The passage of stones into the ureter with subsequent acute obstruction, proximal urinary tract dilation, and spasm is associated with classic renal colic.

Acute onset of severe flank pain radiating to the groin, gross or microscopic hematuria, nausea, and vomiting not associated with an acute abdomen are symptoms that most likely indicate renal colic caused by an acute ureteral or renal pelvic obstruction from a calculus. Renal colic pain rarely, if ever, occurs without obstruction.

Patients with large renal stones known as staghorn calculi (see the image below) are often relatively asymptomatic. The term "staghorn" refers to the presence of a branched kidney stone occupying the renal pelvis and at least one calyceal system. Such calculi usually manifest as infection and hematuria rather than as acute pain.

Asymptomatic bilateral obstruction, which is uncommon, manifests as symptoms of renal failure.

Important historical features are as follows:

• Duration, characteristics, and location of pain
• History of urinary calculi
• Prior complications related to stone manipulation
• Urinary tract infections
• Loss of renal function
• Family history of calculi
• Solitary or transplanted kidney
• Chemical composition of previously passed stones

Location and characteristics of pain

Most calculi originate within the kidney and proceed distally, creating various degrees of urinary obstruction as they become lodged in narrow areas, including the ureteropelvic junction, pelvic brim, and ureterovesical junction. Location and quality of pain are related to position of the stone within the urinary tract. Severity of pain is related to the degree of obstruction, presence of ureteral spasm, and presence of any associated infection.

Stones obstructing the ureteropelvic junction may present with mild-to-severe deep flank pain without radiation to the groin, due to distention of the renal capsule. Stones impacted within the ureter cause abrupt, severe, colicky pain in the flank and ipsilateral lower abdomen with radiation to the testicles or the vulvar area. Intense nausea, with or without vomiting, usually is present.

Pain from upper ureteral stones tends to radiate to the flank and lumbar areas. On the right side, this can be confused with cholecystitis or cholelithiasis; on the left, the differential diagnoses include acute pancreatitis, peptic ulcer disease, and gastritis.

Midureteral calculi cause pain that radiates anteriorly and caudally. This midureteral pain in particular can easily mimic appendicitis on the right or acute diverticulitis on the left.

Distal ureteral stones cause pain that tends to radiate into the groin or testicle in the male or labia majora in the female because the pain is referred from the ilioinguinal or genitofemoral nerves.

Stones lodged at the ureterovesical junction also may cause irritative voiding symptoms, such as urinary frequency and dysuria. If a stone is lodged in the intramural ureter, symptoms may appear similar to cystitis or urethritis. These symptoms include suprapubic pain, urinary frequency, urgency, dysuria, stranguria, pain at the tip of the penis, and sometimes various bowel symptoms, such as diarrhea and tenesmus. These symptoms can be confused with pelvic inflammatory disease, ovarian cyst rupture, or torsion and menstrual pain in women.

Calculi that have entered the bladder are usually asymptomatic and are passed relatively easily during urination. Rarely, a patient reports positional urinary retention (obstruction precipitated by standing, relieved by recumbency), which is due to the ball-valve effect of a large stone located at the bladder outlet.

Phases of acute renal colic attack

The actual pain attack tends to occur in somewhat predictable phases, with the pain reaching its peak in most patients within 2 hours of onset. The pain roughly follows the dermatomes of T-10 to S-4. The entire process typically lasts 3-18 hours. Renal colic has been described as having 3 clinical phases.

The first phase is the acute or onset phase. The typical attack starts early in the morning or at night, waking the patient from sleep. In contrast, attacks that begin during the day tend to start slowly and insidiously.

Pain in the acute phase is usually steady, increasingly severe, and continuous, sometimes punctuated by intermittent paroxysms of even more excruciating pain. The pain may increase to maximum intensity in as little as 30 minutes after onset or may take up to 6 hours or longer to peak. The typical patient reaches maximum pain 1-2 hours after the start of the renal colic attack.

The second phase is the constant phase. Once the pain reaches maximum intensity, it tends to remain constant until it is either treated or allowed to diminish spontaneously. The period of sustained maximal pain is called the constant phase of the renal colic attack. This phase usually lasts 1-4 hours but can persist longer than 12 hours in some cases. Most patients arrive in the ED during this phase of the attack.

The third phase is the abatement or relief phase. During this final phase, the pain diminishes fairly quickly, and patients finally feel relief. Relief can occur spontaneously at any time after the initial onset of the colic. Patients may fall asleep, especially if they have been given strong analgesic medication. Upon awakening, the patient notices that the pain has disappeared. This final phase of the attack most commonly lasts 1.5-3 hours.

Other symptoms

Nausea and vomiting occur in at least 50% of patients with acute renal colic. Nausea is caused by the common innervation pathway of the renal pelvis, stomach, and intestines through the celiac axis and vagal nerve afferents. This is often compounded by the effects of narcotic analgesics, which often induce nausea and vomiting through a direct effect on gastrointestinal (GI) motility and an indirect effect on the chemoreceptor trigger zone in the medulla oblongata. Nonsteroidal anti-inflammatory drugs (NSAIDs) can often cause gastric irritation and GI upset.

The presence of a renal or ureteral calculus is not a guarantee that the patient does not have some other, unrelated medical problem causing the GI symptoms.

In some cases, a stone may pass before the definitive imaging procedure has been completed. In these cases, residual inflammation and edema still may cause some transient or diminishing obstruction and pain even without any stone being positively identified.

The classic presentation for a patient with acute renal colic is the sudden onset of severe pain originating in the flank and radiating inferiorly and anteriorly. The pain is usually, but not always, associated with microscopic hematuria, nausea, and vomiting. Dramatic costovertebral angle tenderness is common; this pain can move to the upper or lower abdominal quadrant as a ureteral stone migrates distally. However, the rest of the examination findings are often unremarkable.

Abdominal examination usually is unremarkable. Bowel sounds may be hypoactive, a reflection of mild ileus, which is not uncommon in patients with severe, acute pain. Peritoneal signs are usually absent—an important consideration in distinguishing renal colic from other sources of flank or abdominal pain. Testicles may be painful but should not be very tender and should appear normal.

Unlike patients with an acute abdomen, who usually try to lie absolutely still, patients with renal colic tend to move constantly, seeking a more comfortable position. (However, patients with pyonephrosis also tend to remain motionless.) The classic patient with renal colic is writhing in pain, pacing about, and unable to lie still, in contrast to a patient with peritoneal irritation, who remains motionless to minimize discomfort.

Findings should correlate with the reports of pain, so that complicating factors (eg, urinary extravasation, abscess formation) can be detected. Beyond this, the specific location of tenderness does not always correlate with the exact location of the stone, although the calculus is often in the general area of maximum discomfort.

Approximately 85% of all patients with renal colic demonstrate at least microscopic hematuria, which means that 15% of all patients with kidney stones do not have hematuria. Lack of hematuria alone does not exclude the diagnosis of acute renal colic. Tachycardia and hypertension are relatively common in these cases, even in patients with no prior personal history of abnormal cardiac or blood pressure problems.

Fever is not part of the presentation of uncomplicated nephrolithiasis. The presence of pyuria, fever, leukocytosis, or bacteriuria suggests the possibility of a urinary infection and the potential for an infected obstructed renal unit or pyonephrosis. Such a condition is potentially life threatening and should be treated as a surgical emergency.

In patients older than 60 years presenting with severe abdominal pain and with no prior history of renal stones, look carefully for physical signs of abdominal aortic aneurysm (AAA) (see Abdominal Aortic Aneurysm ).

The morbidity of urinary tract calculi is primarily due to obstruction with its associated pain, although nonobstructing calculi can still produce considerable discomfort. Conversely, patients with obstructing calculi may be asymptomatic, which is the usual scenario in patients who experience loss of renal function due to chronic untreated obstruction. Stone-induced hematuria is frightening to the patient but is rarely dangerous by itself.

Serious complications of urinary tract stone disease include the following:

• Abscess formation
• Serious infection of the kidney that diminishes renal function
• Urinary fistula formation
• Ureteral scarring and stenosis
• Ureteral perforation
• Extravasation
• Renal loss due to long-standing obstruction

Infected hydronephrosis is the most deadly complication because the presence of infection adjacent to the highly vascular renal parenchyma places the patient at risk for rapidly progressive sepsis and death.

A ureteral stone associated with obstruction and upper UTI is a true urologic emergency. Complications include perinephric abscess, urosepsis, and death. Immediate involvement of the urologist is essential.

Calyceal rupture with perinephric urine extravasation due to high intracaliceal pressures occasionally is seen and usually is treated conservatively.

Complete ureteral obstruction may occur in patients with tightly impacted stones. This is best diagnosed via IVP and is not discernible on noncontrast CT scan. Patients with 2 healthy kidneys can tolerate several days of complete unilateral ureteral obstruction without long-term effects on the obstructed kidney. If a patient with complete obstruction is well hydrated and pain and vomiting are well controlled, the patient can be discharged from the ED with urologic follow-up within 1-2 days.

[Guideline] Turk C, Neisius A, Petrik A, Seitz C, Skolarikos A, Thomas K. Guidelines on urolithiasis. European Association of Urology. Available at https://uroweb.org/guideline/urolithiasis/ . March 2023; Accessed: July 26, 2023.

Scales CD Jr, Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol . 2012 Jul. 62 (1):160-5. [QxMD MEDLINE Link] . [Full Text] .

Ziemba JB, Matlaga BR. Epidemiology and economics of nephrolithiasis. Investig Clin Urol . 2017 Sep. 58 (5):299-306. [QxMD MEDLINE Link] . [Full Text] .

Saigal CS, Joyce G, Timilsina AR, Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management?. Kidney Int . 2005 Oct. 68 (4):1808-14. [QxMD MEDLINE Link] .

Evan AP, Coe FL, Lingeman JE, Shao Y, Sommer AJ, Bledsoe SB, et al. Mechanism of formation of human calcium oxalate renal stones on Randall's plaque. Anat Rec (Hoboken) . 2007 Oct. 290(10):1315-23. [QxMD MEDLINE Link] .

Chandhoke PS. Evaluation of the recurrent stone former. Urol Clin North Am . 2007 Aug. 34(3):315-22. [QxMD MEDLINE Link] .

Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med . 2002 Jan 10. 346(2):77-84. [QxMD MEDLINE Link] .

Russinko PJ, Agarwal S, Choi MJ, Kelty PJ. Obstructive nephropathy secondary to sulfasalazine calculi. Urology . 2003 Oct. 62(4):748. [QxMD MEDLINE Link] .

Thomas A, Woodard C, Rovner ES, Wein AJ. Urologic complications of nonurologic medications. Urol Clin North Am . 2003 Feb. 30(1):123-31. [QxMD MEDLINE Link] .

Whelan C, Schwartz BF. Bilateral guaifenesin ureteral calculi. Urology . 2004 Jan. 63(1):175-6. [QxMD MEDLINE Link] .

Wang S, Huang X, Xu Q, Xu T. Research Progress of Mechanisms of Ceftriaxone Associated Nephrolithiasis. Mini Rev Med Chem . 2017. 17 (17):1584-1587. [QxMD MEDLINE Link] .

Tasian GE, Jemielita T, Goldfarb DS, Copelovitch L, Gerber JS, Wu Q, et al. Oral Antibiotic Exposure and Kidney Stone Disease. J Am Soc Nephrol . May 10, 2018. [Full Text] .

Sayer JA. Progress in Understanding the Genetics of Calcium-Containing Nephrolithiasis. J Am Soc Nephrol . 2017 Mar. 28 (3):748-759. [QxMD MEDLINE Link] .

Daga A, Majmundar AJ, Braun DA, Gee HY, Lawson JA, et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int . 2017 Sep 8. [QxMD MEDLINE Link] .

van der Wijst J, van Goor MK, Schreuder MF, Hoenderop JG. TRPV5 in renal tubular calcium handling and its potential relevance for nephrolithiasis. Kidney Int . 2019 Dec. 96 (6):1283-1291. [QxMD MEDLINE Link] .

Pearle MS, Calhoun EA, Curhan GC. Urologic diseases in America project: urolithiasis. J Urol . 2005 Mar. 173(3):848-57. [QxMD MEDLINE Link] .

Tundo G, Vollstedt A, Meeks W, Pais V. Beyond Prevalence: Annual Cumulative Incidence of Kidney Stones in the United States. J Urol . 2021 Jun. 205 (6):1704-1709. [QxMD MEDLINE Link] .

Worcester EM, Coe FL. Nephrolithiasis. Prim Care . 2008 Jun. 35(2):369-91, vii. [QxMD MEDLINE Link] . [Full Text] .

Tasian GE, Ross ME, Song L, Sas DJ, Keren R, Denburg MR, et al. Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 2012. Clin J Am Soc Nephrol . 2016 Mar 7. 11 (3):488-96. [QxMD MEDLINE Link] .

Tasian GE, Copelovitch L. Evaluation and medical management of kidney stones in children. J Urol . 2014 Nov. 192 (5):1329-36. [QxMD MEDLINE Link] .

Dai JC, Nicholson TM, Chang HC, Desai AC, Sweet RM, Harper JD, et al. Nephrolithiasis in Pregnancy: Treating for Two. Urology . 2021 May. 151:44-53. [QxMD MEDLINE Link] .

Cicerello E, Mangano MS, Cova G, Ciaccia M. Changing in gender prevalence of nephrolithiasis. Urologia . 2021 May. 88 (2):90-93. [QxMD MEDLINE Link] .

Moore CL, Bomann S, Daniels B, Luty S, Molinaro A, Singh D, et al. Derivation and validation of a clinical prediction rule for uncomplicated ureteral stone--the STONE score: retrospective and prospective observational cohort studies. BMJ . 2014 Mar 26. 348:g2191. [QxMD MEDLINE Link] . [Full Text] .

Borrero E, Queral LA. Symptomatic abdominal aortic aneurysm misdiagnosed as nephroureterolithiasis. Ann Vasc Surg . 1988 Apr. 2(2):145-9. [QxMD MEDLINE Link] .

Lindqvist K, Hellström M, Holmberg G, Peeker R, Grenabo L. Immediate versus deferred radiological investigation after acute renal colic: a prospective randomized study. Scand J Urol Nephrol . 2006. 40(2):119-24. [QxMD MEDLINE Link] .

Bove P, Kaplan D, Dalrymple N, Rosenfield AT, Verga M, Anderson K, et al. Reexamining the value of hematuria testing in patients with acute flank pain. J Urol . 1999 Sep. 162(3 Pt 1):685-7. [QxMD MEDLINE Link] .

Press SM, Smith AD. Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain. Urology . 1995 May. 45(5):753-7. [QxMD MEDLINE Link] .

Dundee P, Bouchier-Hayes D, Haxhimolla H, Dowling R, Costello A. Renal tract calculi: comparison of stone size on plain radiography and noncontrast spiral CT scan. J Endourol . 2006 Dec. 20(12):1005-9. [QxMD MEDLINE Link] .

Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol . 2000 Aug. 164(2):308-10. [QxMD MEDLINE Link] .

Pais VM Jr, Payton AL, LaGrange CA. Urolithiasis in pregnancy. Urol Clin North Am . 2007 Feb. 34(1):43-52. [QxMD MEDLINE Link] .

Jindal G, Ramchandani P. Acute flank pain secondary to urolithiasis: radiologic evaluation and alternate diagnoses. Radiol Clin North Am . 2007 May. 45(3):395-410, vii. [QxMD MEDLINE Link] .

Middleton WD, Dodds WJ, Lawson TL, Foley WD. Renal calculi: sensitivity for detection with US. Radiology . 1988 Apr. 167(1):239-44. [QxMD MEDLINE Link] .

Cauni V, Multescu R, Geavlete P, Geavlete B. [The importance of Doppler ultrasonographic evaluation of the ureteral jets in patients with obstructive upper urinary tract lithiasis]. Chirurgia (Bucur) . 2008 Nov-Dec. 103(6):665-8. [QxMD MEDLINE Link] .

Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA . 2004 May 19. 291(19):2328-34. [QxMD MEDLINE Link] .

Gdor Y, Faddegon S, Krambeck AE, et al. Multi-institutional assessment of ureteroscopic laser papillotomy for chronic flank pain associated with papillary calcifications. J Urol . 2011 Jan. 185(1):192-7. [QxMD MEDLINE Link] .

Neville A, Hatem SF. Renal medullary carcinoma: unsuspected diagnosis at stone protocol CT. Emerg Radiol . 2007 Sep. 14(4):245-7. [QxMD MEDLINE Link] .

Dusseault BN, Croce KJ, Pais VM Jr. Radiographic characteristics of sulfadiazine urolithiasis. Urology . 2009 Apr. 73(4):928.e5-6. [QxMD MEDLINE Link] .

Narepalem N, Sundaram CP, Boridy IC, Yan Y, Heiken JP, Clayman RV. Comparison of helical computerized tomography and plain radiography for estimating urinary stone size. J Urol . 2002 Mar. 167(3):1235-8. [QxMD MEDLINE Link] .

Kishore TA, Pedro RN, Hinck B, Monga M. Estimation of size of distal ureteral stones: noncontrast CT scan versus actual size. Urology . 2008 Oct. 72(4):761-4. [QxMD MEDLINE Link] .

Chiou T, Meagher MF, Berger JH, Chen TT, Sur RL, Bechis SK. Software-Estimated Stone Volume Is Better Predictor of Spontaneous Passage for Acute Nephrolithiasis. J Endourol . 2023 Jan. 37 (1):85-92. [QxMD MEDLINE Link] .

Panthier F, Traxer O, Yonneau L, Lebret T, Berthe L, Illoul L, et al. Evaluation of a free 3D software for kidney stones' surgical planning: "kidney stone calculator" a pilot study. World J Urol . 2021 Sep. 39 (9):3607-3614. [QxMD MEDLINE Link] . [Full Text] .

Katz DS, Lane MJ, Sommer FG. Unenhanced helical CT of ureteral stones: incidence of associated urinary tract findings. AJR Am J Roentgenol . 1996 Jun. 166(6):1319-22. [QxMD MEDLINE Link] .

Smith RC, Verga M, Dalrymple N, McCarthy S, Rosenfield AT. Acute ureteral obstruction: value of secondary signs of helical unenhanced CT. AJR Am J Roentgenol . 1996 Nov. 167(5):1109-13. [QxMD MEDLINE Link] .

Smergel E, Greenberg SB, Crisci KL, Salwen JK. CT urograms in pediatric patients with ureteral calculi: do adult criteria work?. Pediatr Radiol . 2001 Oct. 31(10):720-3. [QxMD MEDLINE Link] .

[Guideline] Coursey CA, Casalino DD, Remer EM, Arellano RS, Bishoff JT, Dighe M, et al. ACR Appropriateness Criteria® acute onset flank pain--suspicion of stone disease. Ultrasound Q . 2012 Sep. 28 (3):227-33. [QxMD MEDLINE Link] . [Full Text] .

Sudah M, Vanninen R, Partanen K, Heino A, Vainio P, Ala-Opas M. MR urography in evaluation of acute flank pain: T2-weighted sequences and gadolinium-enhanced three-dimensional FLASH compared with urography. Fast low-angle shot. AJR Am J Roentgenol . 2001 Jan. 176(1):105-12. [QxMD MEDLINE Link] .

[Guideline] Assimos DG, Krambeck A, Miller NL, et al. Surgical Management of Stones: American Urological Association/Endourological Society Guideline. American Urological Association. Available at https://www.auanet.org/guidelines-and-quality/guidelines/kidney-stones-surgical-management-guideline . 2016; Accessed: July 27, 2023.

Mariappan P, Loong CW. Midstream urine culture and sensitivity test is a poor predictor of infected urine proximal to the obstructing ureteral stone or infected stones: a prospective clinical study. J Urol . 2004 Jun. 171(6 Pt 1):2142-5. [QxMD MEDLINE Link] .

St Lezin M, Hofmann R, Stoller ML. Pyonephrosis: diagnosis and treatment. Br J Urol . 1992 Oct. 70(4):360-3. [QxMD MEDLINE Link] .

Jeffrey RB, Laing FC, Wing VW, Hoddick W. Sensitivity of sonography in pyonephrosis: a reevaluation. AJR Am J Roentgenol . 1985 Jan. 144(1):71-3. [QxMD MEDLINE Link] .

Schneider K, Helmig FJ, Eife R, Belohradsky BH, Kohn MM, Devens K, et al. Pyonephrosis in childhood--is ultrasound sufficient for diagnosis?. Pediatr Radiol . 1989. 19(5):302-7. [QxMD MEDLINE Link] .

Fultz PJ, Hampton WR, Totterman SM. Computed tomography of pyonephrosis. Abdom Imaging . 1993. 18(1):82-7. [QxMD MEDLINE Link] .

Wu TT, Lee YH, Tzeng WS, Chen WC, Yu CC, Huang JK. The role of C-reactive protein and erythrocyte sedimentation rate in the diagnosis of infected hydronephrosis and pyonephrosis. J Urol . 1994 Jul. 152(1):26-8. [QxMD MEDLINE Link] .

Wen CC, Nakada SY. Treatment selection and outcomes: renal calculi. Urol Clin North Am . 2007 Aug. 34(3):409-19. [QxMD MEDLINE Link] .

Pathan SA, Mitra B, Straney LD, Afzal MS, Anjum S, Shukla D, et al. Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial. Lancet . 2016 May 14. 387 (10032):1999-2007. [QxMD MEDLINE Link] .

Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev . 2005 Apr 18. CD004137. [QxMD MEDLINE Link] .

Hollingsworth JM, Canales BK, Rogers MA, Sukumar S, Yan P, Kuntz GM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ . 2016 Dec 1. 355:i6112. [QxMD MEDLINE Link] . [Full Text] .

Labrecque M, Dostaler LP, Rousselle R, Nguyen T, Poirier S. Efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic. A meta-analysis. Arch Intern Med . 1994 Jun 27. 154(12):1381-7. [QxMD MEDLINE Link] .

Larkin GL, Peacock WF 4th, Pearl SM, Blair GA, D'Amico F. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med . 1999 Jan. 17(1):6-10. [QxMD MEDLINE Link] .

Cooper JT, Stack GM, Cooper TP. Intensive medical management of ureteral calculi. Urology . 2000 Oct 1. 56(4):575-8. [QxMD MEDLINE Link] .

Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urol . 2003 Dec. 170(6 Pt 1):2202-5. [QxMD MEDLINE Link] .

Dellabella M, Milanese G, Muzzonigro G. Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi. J Urol . 2005 Jul. 174(1):167-72. [QxMD MEDLINE Link] .

Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM. Nifedipine versus tamsulosin for the management of lower ureteral stones. J Urol . 2004 Aug. 172(2):568-71. [QxMD MEDLINE Link] .

Küpeli B, Irkilata L, Gürocak S, Tunç L, Kiraç M, Karaoglan U, et al. Does tamsulosin enhance lower ureteral stone clearance with or without shock wave lithotripsy?. Urology . 2004 Dec. 64(6):1111-5. [QxMD MEDLINE Link] .

Porpiglia F, Destefanis P, Fiori C, Fontana D. Effectiveness of nifedipine and deflazacort in the management of distal ureter stones. Urology . 2000 Oct 1. 56(4):579-82. [QxMD MEDLINE Link] .

Porpiglia F, Destefanis P, Fiori C, Scarpa RM, Fontana D. Role of adjunctive medical therapy with nifedipine and deflazacort after extracorporeal shock wave lithotripsy of ureteral stones. Urology . 2002 Jun. 59(6):835-8. [QxMD MEDLINE Link] .

Yilmaz E, Batislam E, Basar MM, Tuglu D, Ferhat M, Basar H. The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones. J Urol . 2005 Jun. 173(6):2010-2. [QxMD MEDLINE Link] .

Hollingsworth JM, Rogers MA, Kaufman SR, Bradford TJ, Saint S, Wei JT, et al. Medical therapy to facilitate urinary stone passage: a meta-analysis. Lancet . 2006 Sep 30. 368(9542):1171-9. [QxMD MEDLINE Link] .

[Guideline] Türk C, Knoll T, Seitz C, Skolarikos A, Chapple C, McClinton S, et al. Medical Expulsive Therapy for Ureterolithiasis: The EAU Recommendations in 2016. Eur Urol . 2017 Apr. 71 (4):504-507. [QxMD MEDLINE Link] .

Singh A, Alter HJ, Littlepage A. A systematic review of medical therapy to facilitate passage of ureteral calculi. Ann Emerg Med . 2007 Nov. 50(5):552-63. [QxMD MEDLINE Link] .

Beach MA, Mauro LS. Pharmacologic expulsive treatment of ureteral calculi. Ann Pharmacother . 2006 Jul-Aug. 40(7-8):1361-8. [QxMD MEDLINE Link] .

Ferre RM, Wasielewski JN, Strout TD, Perron AD. Tamsulosin for ureteral stones in the emergency department: a randomized, controlled trial. Ann Emerg Med . 2009 Sep. 54(3):432-9, 439.e1-2. [QxMD MEDLINE Link] .

Pickard R, Starr K, MacLennan G, Lam T, Thomas R, Burr J, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet . 2015 Jul 25. 386 (9991):341-9. [QxMD MEDLINE Link] . [Full Text] .

Meltzer AC, Burrows PK, Wolfson AB, Hollander JE, Kurz M, Kirkali Z, et al. Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones: A Randomized Clinical Trial. JAMA Intern Med . 2018 Jun 18. [QxMD MEDLINE Link] . [Full Text] .

Springhart WP, Marguet CG, Sur RL, Norris RD, Delvecchio FC, Young MD, et al. Forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial. J Endourol . 2006 Oct. 20(10):713-6. [QxMD MEDLINE Link] .

[Guideline] Preminger GM, Assimos DG, Lingeman JE, Nakada SY, Pearle MS, Wolf JS Jr. Chapter 1: AUA guideline on management of staghorn calculi: diagnosis and treatment recommendations. J Urol . 2005 Jun. 173(6):1991-2000. [QxMD MEDLINE Link] .

Ramakumar S, Segura JW. Renal calculi. Percutaneous management. Urol Clin North Am . 2000 Nov. 27(4):617-22. [QxMD MEDLINE Link] .

Maloney ME, Marguet CG, Zhou Y, Kang DE, Sung JC, Springhart WP, et al. Progressive increase of lithotripter output produces better in-vivo stone comminution. J Endourol . 2006 Sep. 20 (9):603-6. [QxMD MEDLINE Link] .

Demirci D, Sofikerim M, Yalçin E, Ekmekçioğlu O, Gülmez I, Karacagil M. Comparison of conventional and step-wise shockwave lithotripsy in management of urinary calculi. J Endourol . 2007 Dec. 21 (12):1407-10. [QxMD MEDLINE Link] .

Pareek G, Hedican SP, Lee FT Jr, Nakada SY. Shock wave lithotripsy success determined by skin-to-stone distance on computed tomography. Urology . 2005 Nov. 66(5):941-4. [QxMD MEDLINE Link] .

Fankhauser CD, Kranzbühler B, Poyet C, Hermanns T, Sulser T, Steurer J. Long-term Adverse Effects of Extracorporeal Shock-wave Lithotripsy for Nephrolithiasis and Ureterolithiasis: A Systematic Review. Urology . 2015 May. 85 (5):991-1006. [QxMD MEDLINE Link] .

Ault A. Extracorporeal Shockwave Lithotripsy Falling Out of Favor. Medscape Medical News. Available at https://www.medscape.com/viewarticle/845931 . June 4, 2015; Accessed: July 27, 2023.

Aboumarzouk OM, Kata SG, Keeley FX, McClinton S, Nabi G. Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi. Cochrane Database Syst Rev . 2012 May 16. 5:CD006029. [QxMD MEDLINE Link] .

Song T, Liao B, Zheng S, Wei Q. Meta-analysis of postoperatively stenting or not in patients underwent ureteroscopic lithotripsy. Urol Res . 2012 Feb. 40(1):67-77. [QxMD MEDLINE Link] .

Afane JS, Olweny EO, Bercowsky E, Sundaram CP, Dunn MD, Shalhav AL, et al. Flexible ureteroscopes: a single center evaluation of the durability and function of the new endoscopes smaller than 9Fr. J Urol . 2000 Oct. 164 (4):1164-8. [QxMD MEDLINE Link] .

Ho CC, Hee TG, Hong GE, Singam P, Bahadzor B, Md Zainuddin Z. Outcomes and Safety of Retrograde Intra-Renal Surgery for Renal Stones Less Than 2 cm in Size. Nephrourol Mon . 2012 Spring. 4 (2):454-7. [QxMD MEDLINE Link] .

Wen J, Xu G, Du C, Wang B. Minimally invasive percutaneous nephrolithotomy versus endoscopic combined intrarenal surgery with flexible ureteroscope for partial staghorn calculi: A randomised controlled trial. Int J Surg . 2016 Apr. 28:22-7. [QxMD MEDLINE Link] .

Ruhayel Y, Tepeler A, Dabestani S, MacLennan S, Petřík A, Sarica K, et al. Tract Sizes in Miniaturized Percutaneous Nephrolithotomy: A Systematic Review from the European Association of Urology Urolithiasis Guidelines Panel. Eur Urol . 2017 Aug. 72 (2):220-235. [QxMD MEDLINE Link] .

Dede O, Sancaktutar AA, Dağguli M, Utangaç M, Baş O, Penbegul N. Ultra-mini-percutaneous nephrolithotomy in pediatric nephrolithiasis: Both low pressure and high efficiency. J Pediatr Urol . 2015 Apr 28. [QxMD MEDLINE Link] .

Khalaf I, Salih E, El-Mallah E, Farghal S, Abdel-Raouf A. The outcome of open renal stone surgery calls for limitation of its use: A single institution experience. African Journal of Urology . June 2013. [Full Text] .

Assimos DG. Anatrophic nephrolithotomy. Urology . 2001 Jan. 57 (1):161-5. [QxMD MEDLINE Link] .

Ganpule AP, Prashant J, Desai MR. Laparoscopic and robot-assisted surgery in the management of urinary lithiasis. Arab J Urol . 2012 Mar. 10 (1):32-9. [QxMD MEDLINE Link] .

Giedelman C, Arriaga J, Carmona O, de Andrade R, Banda E, Lopez R, et al. Laparoscopic anatrophic nephrolithotomy: developments of the technique in the era of minimally invasive surgery. J Endourol . 2012 May. 26 (5):444-50. [QxMD MEDLINE Link] .

King SA, Klaassen Z, Madi R. Robot-assisted anatrophic nephrolithotomy: description of technique and early results. J Endourol . 2014 Mar. 28 (3):325-9. [QxMD MEDLINE Link] .

Ghani KR, Rogers CG, Sood A, Kumar R, Ehlert M, Jeong W, et al. Robot-assisted anatrophic nephrolithotomy with renal hypothermia for managing staghorn calculi. J Endourol . 2013 Nov. 27 (11):1393-8. [QxMD MEDLINE Link] .

Somani BK, Dellis A, Liatsikos E, Skolarikos A. Review on diagnosis and management of urolithiasis in pregnancy: an ESUT practical guide for urologists. World J Urol . 2017 Nov. 35 (11):1637-1649. [QxMD MEDLINE Link] .

Wang Z, Xu L, Su Z, Yao C, Chen Z. Invasive management of proximal ureteral calculi during pregnancy. Urology . 2014 Feb 6. [QxMD MEDLINE Link] .

Kingo PS, Ryhammer AM, Fuglsig S. Clinical experience with the Swiss lithoclast master in treatment of bladder calculi. J Endourol . 2014 Oct. 28 (10):1178-82. [QxMD MEDLINE Link] .

Chew BH, Arsovska O, Lange D, Wright JE, Beiko DT, Ghiculete D, et al. The Canadian StoneBreaker trial: a randomized, multicenter trial comparing the LMA StoneBreaker™ and the Swiss LithoClast® during percutaneous nephrolithotripsy. J Endourol . 2011 Sep. 25 (9):1415-9. [QxMD MEDLINE Link] .

El-Gamal O, El-Bendary M, Ragab M, Rasheed M. Role of combined use of potassium citrate and tamsulosin in the management of uric acid distal ureteral calculi. Urol Res . 2012 Jun. 40 (3):219-24. [QxMD MEDLINE Link] .

[Guideline] Preminger GM, Tiselius HG, Assimos DG, Alken P, Buck C, Gallucci M, et al. 2007 guideline for the management of ureteral calculi. J Urol . 2007 Dec. 178 (6):2418-34. [QxMD MEDLINE Link] . [Full Text] .

Dhayat NA, Bonny O, Roth B, et al. Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence. N Engl J Med . 2023 Mar 2. 388 (9):781-791. [QxMD MEDLINE Link] .

• Small renal calculus that would likely respond to extracorporeal shockwave lithotripsy.
• Complete staghorn calculus that fills the collecting system of the kidney (no intravenous contrast material in this patient). Although many staghorn calculi are struvite (related to infection with urease-splitting bacteria), the density of this stone suggests that it may be metabolic in origin and is likely composed of calcium oxalate. Percutaneous nephrostolithotomy or perhaps even open surgical nephrolithotomy is required to remove this stone.
• Distal ureteral stone observed through a small, rigid ureteroscope prior to ballistic lithotripsy and extraction. The small caliber and excellent optics of today's endoscopes greatly facilitate minimally invasive treatment of urinary stones.
• Two calculi in a dependent calyx of the kidney (lower pole) visualized through a flexible fiberoptic ureteroscope. In another location, these calculi might have been treated with extracorporeal shockwave lithotripsy (ESWL), but, after being counseled regarding the lower success rate of ESWL for stones in a dependent location, the patient elected ureteroscopy. Note that the image provided by fiberoptics, although still acceptable, is inferior to that provided by the rod-lens optics of the rigid ureteroscope in the previous picture.
• Nephrolithiasis: acute renal colic. Anatomy of the ureter.
• Nephrolithiasis: acute renal colic. Distribution of nerves in the flank.
• Nephrolithiasis: acute renal colic. Nerve supply of the kidney.
• Nephrolithiasis: acute renal colic. Renal colic and flank pain.
• Nephrolithiasis: acute renal colic. Distribution of renal and ureteral pain.
• Noncontrast helical CT scan of the abdomen demonstrating a stone at the right ureterovesical junction.
• Intravenous pyelogram (IVP) demonstrating dilation of the right renal collecting system and right ureter consistent with right ureterovesical stone.
• Table. Intravenous Pyelography Versus CT Scanning: Which Is Better?

Contributor Information and Disclosures

Chirag N Dave, MD Physician in Sexual and Male Reproductive Medicine and Urology, Advanced Urology Institute of Georgia Chirag N Dave, MD is a member of the following medical societies: American Urological Association , Sexual Medicine Society of North America Disclosure: Nothing to disclose.

Seema Mehta, DO, MSc Resident Physician, Department of Family Medicine, University of Michigan Medical School Disclosure: Nothing to disclose.

Kristen Meier, MD Assistant Professor and Pediatric Urologist, Children’s Mercy Hospital Kristen Meier, MD is a member of the following medical societies: Alpha Omega Alpha , American Urological Association , Phi Beta Kappa , Phi Kappa Phi , Society for Pediatric Urology Disclosure: Nothing to disclose.

Sugandh Shetty, MD, FRCS Associate Professor of Urology, Oakland University William Beaumont School of Medicine; Attending Physician, Department of Urology, William Beaumont Hospital Sugandh Shetty, MD, FRCS is a member of the following medical societies: American Urological Association Disclosure: Nothing to disclose.

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Bradley Fields Schwartz, DO, FACS Professor of Urology, Frank and Linda Vala Endowed Chair of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Division of Urology, Southern Illinois University School of Medicine Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons , American Urological Association , Association of Military Osteopathic Physicians and Surgeons , Endourological Society , Society of Laparoscopic and Robotic Surgeons , Society of University Urologists Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Endourological Society Board of Directors<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cook Medical<br/>Received research grant from: Cook Medical.

David S Howes, MD Professor of Medicine and Pediatrics, Residency Program Director Emeritus, Section of Emergency Medicine, University of Chicago, University of Chicago, The Pritzker School of Medicine David S Howes, MD is a member of the following medical societies: American Academy of Emergency Medicine , American College of Emergency Physicians , Society for Academic Emergency Medicine Disclosure: Nothing to disclose.

Richard H Sinert, DO Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Vice-Chair in Charge of Research, Department of Emergency Medicine, Kings County Hospital Center Richard H Sinert, DO is a member of the following medical societies: American College of Physicians , Society for Academic Emergency Medicine Disclosure: Nothing to disclose.

Robert E O'Connor, MD, MPH Professor and Chair, Department of Emergency Medicine, University of Virginia Health System Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine , American College of Emergency Physicians , American Heart Association , American Medical Association , National Association of EMS Physicians , Society for Academic Emergency Medicine Disclosure: Nothing to disclose.

Sandy Craig, MD Residency Program Director, Carolinas Medical Center; Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill School of Medicine Sandy Craig, MD is a member of the following medical societies: Alpha Omega Alpha , Society for Academic Emergency Medicine Disclosure: Nothing to disclose.

Stephen W Leslie, MD, FACS Founder and Medical Director, Lorain Kidney Stone Research Center; Associate Professor of Surgery, Creighton University School of Medicine, Chief of Urology, Creighton University Medical Center Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons , American Urological Association , National Kidney Foundation , Ohio State Medical Association Disclosure: Nothing to disclose.

J Stuart Wolf, Jr, MD, FACS David A Bloom Professor of Urology, Associate Chair for Urologic Surgical Services, Director, Division of Endourology and Stone Disease, Department of Urology, University of Michigan Medical School J Stuart Wolf, Jr, MD, FACS is a member of the following medical societies: Catholic Medical Association , Endourological Society , Engineering and Urology Society , Society of Laparoscopic and Robotic Surgeons , Society of University Urologists , Society of Urologic Oncology , American College of Surgeons , American Urological Association Disclosure: Nothing to disclose.

Kassem Faraj Oakland University William Beaumont School of Medicine Kassem Faraj is a member of the following medical societies: American Medical Association , American Medical Student Association/Foundation , American Urological Association , Michigan State Medical Society Disclosure: Nothing to disclose.

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• Nephrolithiasis
• Fast Five Quiz: Kidney Stones (Renal Calculi)
• Hyperuricosuria and Gouty Diathesis
• Fast Five Quiz: Primary Hyperoxaluria Type 1 Signs and Symptoms
• Kidneys, Ureters, and Bladder (KUB) Imaging
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• Kidney stones

If your doctor suspects that you have a kidney stone, you may have diagnostic tests and procedures, such as:

• Blood testing. Blood tests may reveal too much calcium or uric acid in your blood. Blood test results help monitor the health of your kidneys and may lead your doctor to check for other medical conditions.
• Urine testing. The 24-hour urine collection test may show that you're excreting too many stone-forming minerals or too few stone-preventing substances. For this test, your doctor may request that you perform two urine collections over two consecutive days.

Imaging. Imaging tests may show kidney stones in your urinary tract. High-speed or dual energy computerized tomography (CT) may reveal even tiny stones. Simple abdominal X-rays are used less frequently because this kind of imaging test can miss small kidney stones.

Ultrasound, a noninvasive test that is quick and easy to perform, is another imaging option to diagnose kidney stones.

• Analysis of passed stones. You may be asked to urinate through a strainer to catch stones that you pass. Lab analysis will reveal the makeup of your kidney stones. Your doctor uses this information to determine what's causing your kidney stones and to form a plan to prevent more kidney stones.
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• Computerized tomography (CT) urogram
• Intravenous pyelogram

Treatment for kidney stones varies, depending on the type of stone and the cause.

Small stones with minimal symptoms

Most small kidney stones won't require invasive treatment. You may be able to pass a small stone by:

• Drinking water. Drinking as much as 2 to 3 quarts (1.8 to 3.6 liters) a day will keep your urine dilute and may prevent stones from forming. Unless your doctor tells you otherwise, drink enough fluid — ideally mostly water — to produce clear or nearly clear urine.
• Pain relievers. Passing a small stone can cause some discomfort. To relieve mild pain, your doctor may recommend pain relievers such as ibuprofen (Advil, Motrin IB, others) or naproxen sodium (Aleve).
• Medical therapy. Your doctor may give you a medication to help pass your kidney stone. This type of medication, known as an alpha blocker, relaxes the muscles in your ureter, helping you pass the kidney stone more quickly and with less pain. Examples of alpha blockers include tamsulosin (Flomax) and the drug combination dutasteride and tamsulosin (Jalyn).

Large stones and those that cause symptoms

Parathyroid glands

The four tiny parathyroid glands, which lie near the thyroid, make the parathyroid hormone. The hormone plays a role in controlling levels of the minerals calcium and phosphorus in the body.

Kidney stones that are too large to pass on their own or cause bleeding, kidney damage or ongoing urinary tract infections may require more-extensive treatment. Procedures may include:

Using sound waves to break up stones. For certain kidney stones — depending on size and location — your doctor may recommend a procedure called extracorporeal shock wave lithotripsy (ESWL).

ESWL uses sound waves to create strong vibrations (shock waves) that break the stones into tiny pieces that can be passed in your urine. The procedure lasts about 45 to 60 minutes and can cause moderate pain, so you may be under sedation or light anesthesia to make you comfortable.

ESWL can cause blood in the urine, bruising on the back or abdomen, bleeding around the kidney and other adjacent organs, and discomfort as the stone fragments pass through the urinary tract.

Surgery to remove very large stones in the kidney. A procedure called percutaneous nephrolithotomy (nef-row-lih-THOT-uh-me) involves surgically removing a kidney stone using small telescopes and instruments inserted through a small incision in your back.

You will receive general anesthesia during the surgery and be in the hospital for one to two days while you recover. Your doctor may recommend this surgery if ESWL is unsuccessful.

Using a scope to remove stones. To remove a smaller stone in your ureter or kidney, your doctor may pass a thin lighted tube (ureteroscope) equipped with a camera through your urethra and bladder to your ureter.

Once the stone is located, special tools can snare the stone or break it into pieces that will pass in your urine. Your doctor may then place a small tube (stent) in the ureter to relieve swelling and promote healing. You may need general or local anesthesia during this procedure.

Parathyroid gland surgery. Some calcium phosphate stones are caused by overactive parathyroid glands, which are located on the four corners of your thyroid gland, just below your Adam's apple. When these glands produce too much parathyroid hormone (hyperparathyroidism), your calcium levels can become too high and kidney stones may form as a result.

Hyperparathyroidism sometimes occurs when a small, benign tumor forms in one of your parathyroid glands or you develop another condition that leads these glands to produce more parathyroid hormone. Removing the growth from the gland stops the formation of kidney stones. Or your doctor may recommend treatment of the condition that's causing your parathyroid gland to overproduce the hormone.

Prevention of kidney stones may include a combination of lifestyle changes and medications.

Lifestyle changes

You may reduce your risk of kidney stones if you:

Drink water throughout the day. For people with a history of kidney stones, doctors usually recommend drinking enough fluids to pass about 2.1 quarts (2 liters) of urine a day. Your doctor may ask that you measure your urine output to make sure that you're drinking enough water.

If you live in a hot, dry climate or you exercise frequently, you may need to drink even more water to produce enough urine. If your urine is light and clear, you're likely drinking enough water.

• Eat fewer oxalate-rich foods. If you tend to form calcium oxalate stones, your doctor may recommend restricting foods rich in oxalates. These include rhubarb, beets, okra, spinach, Swiss chard, sweet potatoes, nuts, tea, chocolate, black pepper and soy products.
• Choose a diet low in salt and animal protein. Reduce the amount of salt you eat and choose nonanimal protein sources, such as legumes. Consider using a salt substitute, such as Mrs. Dash.

Continue eating calcium-rich foods, but use caution with calcium supplements. Calcium in food doesn't have an effect on your risk of kidney stones. Continue eating calcium-rich foods unless your doctor advises otherwise.

Ask your doctor before taking calcium supplements, as these have been linked to increased risk of kidney stones. You may reduce the risk by taking supplements with meals. Diets low in calcium can increase kidney stone formation in some people.

Ask your doctor for a referral to a dietitian who can help you develop an eating plan that reduces your risk of kidney stones.

Medications

Medications can control the amount of minerals and salts in the urine and may be helpful in people who form certain kinds of stones. The type of medication your doctor prescribes will depend on the kind of kidney stones you have. Here are some examples:

• Calcium stones. To help prevent calcium stones from forming, your doctor may prescribe a thiazide diuretic or a phosphate-containing preparation.
• Uric acid stones. Your doctor may prescribe allopurinol (Zyloprim, Aloprim) to reduce uric acid levels in your blood and urine and a medicine to keep your urine alkaline. In some cases, allopurinol and an alkalizing agent may dissolve the uric acid stones.
• Struvite stones. To prevent struvite stones, your doctor may recommend strategies to keep your urine free of bacteria that cause infection, including drinking fluids to maintain good urine flow and frequent voiding. In rare cases long-term use of antibiotics in small or intermittent doses may help achieve this goal. For instance, your doctor may recommend an antibiotic before and for a while after surgery to treat your kidney stones.
• Cystine stones. Along with suggesting a diet lower in salt and protein, your doctor may recommend that you drink more fluids so that you produce a lot more urine,. If that alone doesn't help, your doctor may also prescribe a medication that increases the solubility of cystine in your urine.
• Percutaneous nephrolithotomy

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Preparing for your appointment

Small kidney stones that don't block your kidney or cause other problems can be treated by your family doctor. But if you have a large kidney stone and experience severe pain or kidney problems, your doctor may refer you to a doctor who treats problems in the urinary tract (urologist or nephrologist).

What you can do

To prepare for your appointment:

• Ask if there's anything you need to do before your appointment, such as limit your diet.
• Write down your symptoms, including any that seem unrelated to kidney stones.
• Keep track of how much you drink and urinate during a 24-hour period.
• Make a list of all medications, vitamins or other supplements that you take.
• Take a family member or friend along, if possible, to help you remember what you discuss with your doctor.
• Write down questions to ask your doctor.

For kidney stones, some basic questions include:

• Do I have a kidney stone?
• What size is the kidney stone?
• Where is the kidney stone located?
• What type of kidney stone do I have?
• Will I need medication to treat my condition?
• Will I need surgery or another procedure?
• What's the chance that I'll develop another kidney stone?
• How can I prevent kidney stones in the future?
• I have other health conditions. How can I best manage them together?
• Do I need to follow any restrictions?
• Should I see a specialist? If so, does insurance typically cover the services of a specialist?
• Is there a generic alternative to the medicine you're prescribing?
• Do you have any educational material that I can take with me? What websites do you recommend?
• Do I need a follow-up visit?

Besides the questions you prepare in advance, don't hesitate to ask any other questions during your appointment as they occur to you.

What to expect from your doctor

Your doctor is likely to ask you a number of questions, such as:

• When did your symptoms begin?
• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• What, if anything, seems to improve your symptoms?
• What, if anything, appears to worsen your symptoms?
• Has anyone else in your family had kidney stones?
• Goldman L, et al., eds. Nephrolithiasis. In: Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Jan. 20, 2020.
• Kidney stones. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/urologic-diseases/kidney-stones. Accessed Jan. 20, 2020.
• McKean SC, et al., eds. Kidney stones. In: Principles and Practice of Hospital Medicine. 2nd ed. McGraw-Hill Education; 2017. https://accessmedicine.mhmedical.com/. Accessed Jan. 20, 2020.
• What are kidney stones? American Urological Association. https://www.urologyhealth.org/urologic-conditions/kidney-stones. Accessed Jan. 20, 2020.
• Kellerman RD, et al. Nephrolithiasis. In: Conn's Current Therapy 2020. Elsevier; 2020. https://www.clinicalkey.com. Accessed Jan. 20, 2020.
• Braswell-Pickering EA. Allscripts EPSi. Mayo Clinic. Nov. 3, 2021.
• Curhan GC, et al. Diagnosis and acute management of suspected nephrolithiasis in adults. https://www.uptodate.com/search/contents. Accessed Jan. 20, 2020.
• Yu ASL, et al., eds. Diagnostic kidney imaging. In: Brenner & Rector's The Kidney. 11th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Jan. 20, 2020.
• Fontenelle LF, et al. Kidney stones: Treatment and prevention. American Family Physician. 2019. https://www.aafp.org/afp/2019/0415/p490.html. Accessed Jan. 20, 2020.
• Preminger GM. Options in the management of renal and ureteral stones in adults. https://www.uptodate.com/search/contents. Accessed Jan. 20, 2020.
• Preventing Kidney Stones

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Definition & Facts for Kidney Stones

In this section:

What are kidney stones?

Do kidney stones have another name, what type of kidney stones do i have, how common are kidney stones, who is more likely to develop kidney stones, what are the complications of kidney stones.

Kidney stones are hard, pebble-like pieces of material that form in one or both of your kidneys when high levels of certain minerals are in your urine. Kidney stones rarely cause permanent damage if treated by a health care professional.

Kidney stones vary in size and shape. They may be as small as a grain of sand or as large as a pea. Rarely, some kidney stones are as big as golf balls. Kidney stones may be smooth or jagged and are usually yellow or brown.

A small kidney stone may pass through your urinary tract on its own, causing little or no pain. A larger kidney stone may get stuck along the way. A kidney stone that gets stuck can block your flow of urine, causing severe pain or bleeding. Learn more about your urinary tract and how it works .

If you have symptoms of kidney stones , including severe pain or bleeding, seek care right away. A doctor, such as a urologist , can treat any pain and prevent further problems, such as a urinary tract infection (UTI) .

The scientific name for a kidney stone is renal calculus or nephrolith. You may hear health care professionals call this condition nephrolithiasis, urolithiasis, or urinary stones.

You probably have one of four main types of kidney stones. Treatment for kidney stones usually depends on their size, location, and what they are made of.

Calcium stones

Calcium stones, including calcium oxalate stones and calcium phosphate stones, are the most common types of kidney stones. Calcium oxalate stones are more common than calcium phosphate stones.

Calcium from food does not increase your chance of having calcium oxalate stones. Normally, extra calcium that isn’t used by your bones and muscles goes to your kidneys and is flushed out with urine. When this doesn’t happen, the calcium stays in the kidneys and joins with other waste products to form a kidney stone.

Uric acid stones

A uric acid stone may form when your urine contains too much acid. Eating a lot of fish, shellfish, and meat—especially organ meat—may increase uric acid in urine.

Struvite stones

Struvite stones may form after you have a UTI. They can develop suddenly and become large quickly.

Cystine stones

Cystine stones result from a disorder called cystinuria that is passed down through families. Cystinuria causes the amino acid cystine to leak through your kidneys and into the urine.

Kidney stones are common and are on the rise. About 11 percent of men and 6 percent of women in the United States have kidney stones at least once during their lifetime. 1

Men are more likely to develop kidney stones than women. If you have a family history of kidney stones, you are more likely to develop them. You are also more likely to develop kidney stones again if you’ve had them once.

You may also be more likely to develop a kidney stone if you don’t drink enough liquids.

People with certain conditions

You are more likely to develop kidney stones if you have certain conditions, including

• a blockage of the urinary tract
• chronic, or long-lasting, inflammation of the bowel
• cystic kidney diseases , which are disorders that cause fluid-filled sacs to form on the kidneys
• digestive problems or a history of gastrointestinal tract surgery
• gout , a disorder that causes painful swelling of the joints
• hypercalciuria , a condition that runs in families in which urine contains unusually large amounts of calcium; this is the most common condition found in people who form calcium stones
• hyperoxaluria , a condition in which urine contains unusually large amounts of oxalate
• hyperparathyroidism , a condition in which the parathyroid glands release too much parathyroid hormone, causing extra calcium in the blood
• hyperuricosuria, a disorder in which too much uric acid is in the urine
• repeated, or recurrent, UTIs
• renal tubular acidosis , a disease that occurs when the kidneys fail to remove acids into the urine, which causes a person’s blood to remain too acidic

People who take certain medicines

You are more likely to develop kidney stones if you are taking one or more of the following medicines over a long period of time:

• diuretics, often called water pills, which help rid your body of water
• calcium-based antacids
• indinavir , a protease inhibitor used to treat HIV infection
• topiramate , an anti- seizure medication

Complications of kidney stones are rare if you seek treatment from a health care professional before problems occur.

If kidney stones are not treated, they can cause

• hematuria , or blood in the urine
• severe pain
• UTIs, including kidney infections
• loss of kidney function

This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by NIDDK is carefully reviewed by NIDDK scientists and other experts.

Kidney Stones

Sep 21, 2014

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Kidney Stones. Wael AlJaroudi, MD Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center. Epidemiology. Epidemiology Kidney stones (also called Nephrolithiasis or urolithiasis) are common health problems

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Presentation Transcript

Kidney Stones Wael AlJaroudi, MD Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center

Epidemiology Epidemiology • Kidney stones (also called Nephrolithiasis or urolithiasis) are common health problems • The prevalence of stone-forming disease rose from 3.8 percent in the late 1970s to 5.2 percent in the late 1980s and early 1990s. • It is more common in men > women, white > African American • It is estimated that 12 % of men and 5 % of women will develop symptomatic kidney stones by the age of 70 • It has been estimated that for patients who have already had a stone, the likelihood of forming a second stone is about 15 percent at one year, 35 to 40 percent at 5 years, and 80 percent at 10 years.

Pathogenesis Pathogenesis For a stone to form, 3 processes occur: • Supersaturation: Cations and anions are charged soluble molecules such as calcium and oxalate. However, at a specific concentration and pH, the equilibrium state of these molecules reach a critical point called supersaturation. Beyond this point, these molecules cannot remain dissolved and will become insoluble and precipitate 2. Nidus: A nidus represents a focus where crystals start precipitating. 3. Aggregation: Aggregation is the process where precipitating crystals accumulate on each others and form a bigger crystal in a geometrical and organized fashion.

Type of kidney stones Type of kidney stones 1.Calcium stones account for 80 % of all kidney stones -Calcium oxalate (monohydrate and dihydrate) are the most common -Calcium phosphate 2.Uric acid stones 3.Struvite stones (composed of magnesium, ammonium, calcium and phosphate) 4.Cystine stones 5.Indinavir stones (limited to HIV-infected patients)

Calcium Stones Calcium stones -Calcium stones are the most common type of kidney stones -Citrate is the most powerful inhibitor of Calcium oxalate stone formation -Hyperoxaluria is the most important factor in the formation of calcium oxalate stone

Calcium Stones (cont.) -Calcium phosphate stones are the second most common calcium stones after calcium oxalate: they are more common in patients with distal RTA1, patients on acetozolamide ( alkaline pH which leads to CaPO4 precipitation). -Calcium stones precipitate in alkaline urine. -They are radio-opaque and are seen on xray films

Calcium stones: Risk factors Calcium stones: Risk factors: 1.Low fluid intake/ Low urine Volume: Increases the concentration of lithogenic factors in the urine. 2. Hypercalciuria: occurs with hypervitaminosis D, distal RTA 1, sarcoidosis, primary hyperpathyroidism, excessive calcium intake. 3. Hypocitraturia: Occurs in patients with RTA 1 or chronic metabolic acidosis. Citrate chelates calcium and prevent stone formation. Citrate is the most powerful inhibitor of calcium stone formation 4. Hyperuricosuria: Occurs with high protein intake resulting in high uric acid production/excretion. Uric acid act as a nidus for crystal formation 5. History of prior calcium stones

Calcium stones: Risk factors (cont.) Risk factors for calcium stones (continued) 6. Hyperoxaluria: Most important factor in calcium oxalate formation. It is present in mildly elevated amount in up to 40 percent of male and 15 percent of female stone formers. Marked hyperoxaluria is usually associated with inflammatory bowel disease and/or malabsorption: free bile acid chelates calcium in the GI tract allowing more oxalate absorption and hence urinary excretion.High Vit C consumption, ethylene glycol are also associated with hyperoxaluria 7. Medullary sponge kidney: Accounts for 10-20% of calcium stone formers 8. RTA type 1: It is associated with hypocitraturia and hypercalciuria and alkaline pH

Calcium stones: Risk factors (cont.) Risk factors for calcium stones (continued) 9. Primary hyperparathyroidism: Associated with hypercalciuria 10. Gout: associated with hyperuricosuria which acts as a nidus 11. HTN: associated with hyperuricosuria 12.High animal protein: results in high uric acid production and hence excretion 13. High NaCl intake: leads to increased urinary calcium excretion 14. Low calcium intake: Results in less oxalate chelation in the GI tract, more oxalate absorption and hence hyperoxaluria

Uric Acid Stone Uric Acid Stone: -Uric acid stones precipitate in acidic urine, mainly with a pH <5.5 -They are radiolucent and do not show on a regular xray film

Uric Acid Stone (cont.) Uric acid Stone Risk factors: 1.Hyperuricosuria - 10-20 % of gout patients overproduce uric acid leading to increased excretion -Inherited enzyme defects leading to purine overproduction (eg. Lych Nyhan syndrome) -Urate overproduction: (myeloproliferative disorders, obesity, lymphoma,hemolysis, glycogen storage disease, ethanol, vit b12 deficiency, chemotherapy..) 2. Chronic diarrhea: Results in bicarbonate loss, acidic concentrated urine which precipitates uric acid stone

Struvite Stones Struvite Stones -Struvite stones occur in patients with chronic urinary infections due to a urease producing organism -The urease enzyme splits urea into ammonium. -Ammonium binds with phosphorus, magnesium and calcium and form the struvite stone -Urease producing bacteria include proteus (most common), pseudomona, yeast, and Staph (PPYS = piss) -They are rapid forming and often cause staghorn calculi -They precipitate faster in alkaline urine -They are less radio-opaque then calcium stones

Cystine Stones Cystine Stones: -Cystine stones develop in patients with cystinuria, an autosomal recessif disease associated with increased excretion of cystine. -They tend to recur very frequently and often can cause urinary obstrcution and compromise kidney function -Heterozygote/carriers of the disease do not form stones -They precipitate faster in acidic urine

Clinical Symptoms • Clinical symptoms: -Kidney stones often are asymptomatic -Usually, the first symptom of a kidney stone is pain. Pain occurs when there is obstruction of the urinary tract and spasm. Pain is colicky, waxes on/off, sharp, often associated with nausea/vomiting. Its location varies with the location of the stone and can migrate to the suprapubic area and groin as the stone moves down the ureter. -Microscopic/macroscopic hematuria -Dysuria

Evaluation of Kidney stones Evaluation of kidney stones -Workup on initial kidney stone includes: calcium level (r/o hyperparathyroidism, hypervitaminosis D), phopsphorus, electrolytes such as bicarbonate (r/o RTA type 1), U/A with culture, and an imaging modality. Although IVP has been the standard, current data shows that CT renal protocol is as sensitive and specific and does not require contrast.

Evaluation of kidney stones Evaluation of kidney stones (continued) -Urinary pH. A pH >7 (alkaline) is usually associated with calcium phosphorus stones and struvite stones. A pH <5.5 (acidic) is usually associated with cystine and uric acid stones -Crystal morphology is helpful in determining the type of stone

Calcium oxalate crystals Calcium oxalate crystals:urine sediment shows envelop shape dihydrate stone (small arrow), and dumbbell shape monohydrate crystals (long arrow) which could also have a needle appearance.

Uric Acid Stone Uric acid stone: Urine sediment shows pleomorphic Rhombic plates or diamond shape crystals

Struvite Stone Struvite stone: Urine sediment shows “coffin lid” crystals

Cystine Crystal Cystine crystal: Urine sediment shows hexagnal Crystals which are pathognomonic of cystine stone

Recurrent kidney stones For recurrent kidney stones, additional work up includes checking for 24 hr urine volume, cystine, calcium, Na, citrate, urea, uric acid, and creatinine excretion. • Men: Calcium <300 (7.5 mmol/day)/ Female: <250 (6.25 mmol/day) Men: Uric acid <800 (4.8 mmol/day)/ Female: <750 (4.5 mmol/day) Men and Female: Oxalate <45 (0.5 mmol/day) • The standard lower limit of normal for citrate is 320 mg for men and women.

Imaging Modality • Imaging modality -IVP used to be the gold standard. -Non-contrast-enhanced helical CT scan has proven to be accurate in detecting of kidney stones -It is important to appreciate that ureteral dilatation without a stone on radiologic examination could represent recent passage of the stone - Renal ultrasonography is an alternative in pregnant women, but this cannot localize ureteral stones, which can often be detected by transvaginal ultrasonography

Imaging Modality (cont.) Imaging Modality: - The stone characteristics on CT scan may suggest the type of stone that is present: - Although magnesium ammonium phosphate and cystine stones are often radiopaque, they are not as dense as stones comprised of calcium oxalate or calcium phosphate. - Calcium phosphate stones are more likely found in the presence of nephrocalcinosis, which is suggestive of renal tubular acidosis. Bilateral calcifications at the corticomedullary junction is typically seen in medullary sponge kidney and in this setting calcium oxalate or calcium phosphate stones may be found - The presence of staghorn calculi favors struvite stones - Uric acid stones are radio-lucent on xray but visible on CT scan

Treatment • Treatment • Non obstructing stone Calcium stone: -Increase fluid intake to 2 L per day. Decrease dietary protein and Na. -If urinary calcium is elevated, evaluate for high Vit D, hyperparathyroidism and treat accordingly Thiazide diuretic decrease hypercalciuria -If hypocitraturia is present, supplement with potassium citrate. If the pH is >6, citrate supplementation should be avoided because of the increased pH alkalanization and higher risk of stone precipitation

Treatment (cont.) • Treatment • Medical management -If hyperoxaluria is present, the approach to intervention depends on the diet and the urine calcium. If the urine calcium is not high, increasing dietary calcium should be considered along with a low oxalate diet. Food with high oxalate content include: • beets rhubarb • chocolate spinach • coffee strawberries • cola tea • nuts wheat bran

Treatment: Medical Management (cont.) • Treatment • Medical management (continued) -If hyperuricosuria is present, lifestyle modification with the aim of reducing uric acid production (i.e. decreased purine intake and weight loss) should be implemented. However, if the urine pH is 6 or higher, the high urine uric acid may not be playing a role as it will stay in solution.Allopurinol can help decrease uric acid in patients who are overproducers. -Do not decrease calcium intake; this will increases oxaluria

Treatment: Medical Management (cont.) Medical management (continued) Uric acid stone -Allopurinol +/- urine alkalinization -Low purine diet -High fluid intake -Avoid urine alkalinization if there is superimposed hypercalciuria

Treatment: Medical Management (cont.) Medical management (continued) Struvite stone -Acidification of the urine -Antibiotics -Removal of the stone -If stones cannot be removed, acetohydroxamic acid (AHA) can be used with long-term antibiotic drugs to prevent the infection that leads to stone growth.

Treatment: Medical Management (cont.) Medical management (continued) Cystine stone -Increased fluid intake -Alkalinization of the urine -Penicillamine forms soluble complexes with cystine but not well tolerated

Surgical Treatment B. Surgical treatment -Surgery should be reserved as an option for cases where other approaches have failed. Surgery may be needed to remove a kidney stone if it: • does not pass after a reasonable period of time and causes constant pain • is too large to pass on its own or is caught in a difficult place • blocks the flow of urine • causes ongoing urinary tract infection • damages kidney tissue or causes constant bleeding • has grown larger (as seen on follow-up x ray studies).

Surgical options Surgical options include: -Extracorporeal shockwave lithotripsy (ESWL): It is the most frequently used procedure for the treatment of kidney stones. In ESWL, shock waves that are created outside the body travel through the skin and body tissues until they hit the denser stones. The stones break down into sand-like particles and are easily passed through the urinary tract in the urine. -Percutaneous nephrolithotomy: It is recommended to remove a stone that is quite large or in a location that does not allow effective use of ESWL. -Ureteroscopic Stone Removal: If a stone is located low in the urether, it might not be amenable to ESWL. A small fiberoptic instrument called a ureteroscope is passed through the urethra and bladder into the ureter and the stone is either mechanically extracted or fragmented with shock wave impulse

2. Which of the following factors is not associated with calcium stones • High uricosuria • High Na diet • High oxaluria • High citraturia • Alkaline pH Go to the next slide for the answer

Answer: d. Uric acid acts as a nidus for calcium stones. High Na diet leads to increased urinary calcium. Oxalate binds to calcium in the urine and precipitates calcium-oxalate crystals if present at high concentrations. Alkaline pH precipitates calcium stones. Citrate is the most powerful inhibitor of calcium oxalate stones

3. True or False. In patients with calcium oxalate stones, decreasing calcium intake will lower urinary calcium excretion and will result in less stone formation. Go to the next slide for the answer

Answer: False. Lowering calcium intake will result in less calcium chelating oxalate in the GI tract, more oxalate absorption and thus urinary excretion. Hyperoxaluria will cause more calcium stone precipitations

4. True/False: Potassium citrate is routinely used in patients with calcium oxalate stones and low urinary citrate. Go to the next slide for the answer

4. Answer: False. Although citrate is a powerful inhibitor of calcium oxalate formation and needed in the urine to prevent stones, it also raises the pH which might cause more calcium stone precipitation, especially calcium phosphate. If the urine pH >6, it should be avoided.

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References: • Pictures of kidney stone crystal morphology are taken from the following site: www.Uptodate.com / Clinical evaluation of kidney stones • Straub M. Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005 Mar;15(2):119-26. • Knoll T, Zollner A. Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol. 2005 Jan;20(1):19-24. • Rao PN. Imaging for kidney stones. World J Urol. 2004 Nov;22(5):323-7. • Caramia G, Di Gregorio L, et. al. Uric acid, phosphate and oxalate stones: treatment and prophylaxis. Urol Int. 2004;72 Suppl 1:24-8. • Marangella M, Bagnis C, et. al. Crystallization inhibitors in the pathophysiology and treatment of nephrolithiasis. Urol Int. 2004;72 Suppl 1:6-10 • Amato M, Lusini ML. Epidemiology of nephrolithiasis today. Urol Int. 2004;72 Suppl 1:1-5. • Putmann SS, Hamilton BD. The use of shock wave lithotripsy for renal calculi. Curr Opin Urol. 2004 Mar;14(2):117-21 • Sandhu C, Anson KM. Urinary tract stones--Part I: role of radiological imaging in diagnosis and treatment planning. Clin Radiol. 2003 Jun;58(6):415-21. • Sandhu C, Anson KM Urinary tract stones--Part II: current status of treatment.Clin Radiol. 2003 Jun;58(6):422-33. Review.

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Recent advances on the mechanisms of kidney stone formation (Review)

1 Department of Urology, People's Hospital of Longhua, Southern Medical University, Shenzhen, Guangdong 518109, P.R. China

2 Central Laboratory, People's Hospital of Longhua, Southern Medical University, Shenzhen, Guangdong 518109, P.R. China

Jianwen Zhang

Associated data.

Not applicable.

Kidney stone disease is one of the oldest diseases known to medicine; however, the mechanisms of stone formation and development remain largely unclear. Over the past decades, a variety of theories and strategies have been developed and utilized in the surgical management of kidney stones, as a result of recent technological advances. Observations from the authors and other research groups suggest that there are five entirely different main mechanisms for kidney stone formation. Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation. Randall's plaques are recognized as the origin of calcium oxalate stone formation. Sex hormones may be key players in the development of nephrolithiasis and may thus be potential targets for new drugs to suppress kidney stone formation. The microbiome, including urease-producing bacteria, nanobacteria and intestinal microbiota, is likely to have a profound effect on urological health, both positive and negative, owing to its metabolic output and other contributions. Lastly, the immune response, and particularly macrophage differentiation, play crucial roles in renal calcium oxalate crystal formation. In the present study, the current knowledge for each of these five aspects of kidney stone formation is reviewed. This knowledge may be used to explore novel research opportunities and improve the understanding of the initiation and development of kidney stones for urologists, nephrologists and primary care.

1. Introduction

Kidney stone disease, also known as nephrolithiasis or urolithiasis, is one of the oldest diseases known to medicine. It is estimated that 1-15% individuals suffer from kidney stone formation at some point during their lifetime, and the prevalence and incidence of kidney stone is reported to be increasing worldwide ( 1 , 2 ). A recent study concluded that the prevalence of kidney stones was 5.8% among Chinese adults (6.5% in men and 5.1% in women), with about 1 in 17 adults currently affected ( 3 ). Without proper treatment, kidney stones can cause the blockage of the ureter, blood in the urine, frequent urinary tract infections, vomiting or painful urination, culminating in the permanent functional damage of the kidneys ( 4 ). The worldwide prevalence of urolithiasis has increased over the past decades. Urolithiasis is often a recurrent and lifelong disease with a recurrence rate of 50% within 5-10 years and 75% within 20 years ( 5 ). Some studies have indicated that an increase in kidney stone occurrence is expected, due to multiple environmental factors, including changes in lifestyle and dietary habits, as well as global warming ( 1 , 4 , 6 ). However, precise factors responsible for the upward prevalence and recurrence of urolithiasis have not been identified yet. Due to its high prevalence in adults of working age, kidney stone disease has a substantial impact on the individual and society, and has become a public health issue, particularly in populations residing in regions with a hot and dry climate ( 7 , 8 ).

There are mainly five types of kidney stones according to the mineralogical composition, including calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite [(magnesium ammonium phosphate), 2.7%], brushite (1.7%) ( 9 , 10 ). Kidney stones can be broadly categorized into calcareous (calcium containing) stones and non-calcareous stones. The most common types of human kidney stones are CaOx and calcium phosphate (CaP), either alone or combined, which are calcareous and radio-opaque stones ( 9 , 11 ). Kidney stones form at a foundation of CaP termed Randall's plaques (RPs), which begins at the basement membranes of thin limbs of the loop of Henle on the renal papillary surface ( 12 ). CaOx and urate stones exhibit a higher occurrence in males, whereas higher percentages of carbapatite and struvite stones are observed in females than in males ( 10 , 13 ). However, the role of sex differences in the pathophysiological mechanisms of urinary stone disease are not yet fully understood.

Regardless of the type, kidney stone formation is a complex and multistep process that includes urinary supersaturation, crystal nucleation, growth and aggregation ( 11 , 14 ). Kidney stone formation is associated with systemic disorders, including diabetes ( 15 ), obesity, cardiovascular diseases, hypertension and metabolic syndrome ( 16 , 17 ). Conversely, nephrolithiasis patients [also known as kidney stone formers (KSF)] are at a risk of developing hypertension ( 18 ), chronic kidney disease (CKD) ( 19 ) and progression to end-stage renal disease (ESRD) ( 20 , 21 ). Multiple promoting factors and inhibitors have been reported to play critical roles in kidney stone formation. For example, hyperoxaluria, hyperuricosuria and phosphaturia are common promoting factors linked to kidney stone formation ( 22 , 23 ); inter-α-inhibitor (IαI), a member of the protease inhibitor family, has been shown to inhibit CaOx crystallization in vitro ( 24 ).

Although details of human stone formation have accumulated, kidney stone formation and growth mechanisms are far from being clarified. The present review provides an update on the mechanisms of kidney stone formation, in order to improve the understanding of kidney stones for urologists, nephrologists and primary care givers.

2. Physicochemical mechanism of kidney stone formation

Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation and is mainly caused by inherited or acquired diseases associated with renal function impairment. Additionally, urinary supersaturation and crystallization are influenced by urine pH and specific concentrations of substance excess, including CaOx, CaP, uric acids and urates, struvite, amino acids (cysteine), purines (2,8-dihydroxyadenine and xanthine) and drugs (e.g., atazanavir, sulfamethoxazole, amoxicillin, ceftriaxone) ( 25 , 26 ). Additionally, crystal formation and development are influenced by multiple modulator molecules, which are known as receptors, promoters and inhibitors.

Promoters of stone formation

A number of receptors or receptor-like features have been reported to play critical roles in crystal-cell interaction, which is recognized as the most important process for crystal retention in kidney ( 8 , 27 ). Recently, protein alterations in a CaOx monohydrate (COM) crystal-cell interaction model were screened by the authors, and 1,141 differentially expressed proteins (DEPs) were identified in COM treated HK-2 cells ( 28 ). Proteins and glycosaminoglycan like CD44, nucleolin, hyaluronan (HA), heat shock protein 90 (HSP90) ( 29 ), Annexin II ( 30 ) and osteopontin (OPN) ( 28 , 31 ), have been reported to act as stone formation modulators, which has been thoroughly reviewed previously ( 32 ). Several structures and molecular components also play the role of receptor in crystal attachments, including the phosphatidylserine component of the lipid bilayer and the acidic side chains of proteins ( 33 ). Calcium, oxalate, urate and phosphate ions are the main promoters of crystal formation, which can promote crystallization of stone constituents or their aggregation through the activation of several mechanisms. Ketha et al ( 34 ) demonstrated that the first time nephrolithiasis patients had increased serum calcium and 1,25(OH)2D levels than the corresponding healthy individual serum calcium levels, suggesting that stone formation is a manifestation of altered calcium and vitamin D regulation. Higher serum calcium concentration acts as a promoter in lithogenesis, which directly regulated by the calcium-sensing receptor (CaSR) through different pathways ( 35 ). Similarly, urate and phosphate ions have also been reported to promote heterogeneous nucleation and enhance the attachment of crystals to epitheliums ( 36 , 37 ). Another important promoter of stone formation is urine pH ( 38 ). Low pH urine may lead to CaOx crystallization and crystal precipitation ( 39 ). High-alkaline urine may also promote precipitation and nucleation of CaOx crystals ( 40 , 41 ). Lysozyme and lactoferrin are two most recently identified proteins that promote COM growth through the acceleration of layer advancement rate on crystal surfaces ( 42 ).

Inhibitors of stone formation

Normal urine contains numerous inhibitors that act both in competition and cooperation, consequently decrease crystallization and inhibit crystals aggregation and/or adhesion to the tubular epithelial cells ( 43 , 44 ). These inhibitors can be divided into three groups: Anions, metallic cations and macromolecules. Anions such as citrate, can inhibit crystal growth very efficiently, at concentrations above 0.1 mM ( 45 , 46 ). A majority of nephrolithiasis patients exhibited a decrease in citrate excretion. Alkali supplements are widely used for hypocitraturic recurrent nephrolithiasis patients to restore citrate excretion ( 47 , 48 ). Hydroxycitrate is a structural analog of citrate, which has been reported to show equivalent capacity in forming complexes with calcium, in order to inhibit crystallization ( 49 , 50 ). Metallic cations such as magnesium, have been reported to inhibit crystal growth and aggregation, which is synergistic with citrate in acidic environments ( 51 - 53 ). Macromolecules are the most effective inhibitors of crystal growth. More specifically, OPN, Tamm-Horsfall protein (THP), urinary prothrombin fragment 1 (UPTF-1), nephrocalcin (NC) and some subunits of the serum IαI are able to inhibit crystal growth, aggregation and/or adhesion to the tubular cells ( 11 , 38 , 45 ).

However, there is a competition between supersaturation and inhibitors of crystallization as mentioned above, which ultimately determines the pattern of crystalluria in nephrolithiasis patients and healthy individuals ( 54 ). As a consequence of the increased promoters and reduced inhibitors, crystal formation and kidney stone occurrence have been observed ( Fig. 1 ).

Physicochemical mechanisms of kidney stone formation. The reduced inhibitors (left panel) and increased promoters (right panel) are suggested to play critical roles in kidney stone formation.

3. Randall's plaque and calcium oxalate stone formation

RPs, first proposed by Alexander Randall in 1937 ( 55 ), are regions of subepithelial mineralized tissue at the papillary tip, surrounding the openings of the ducts of Bellini containing CaP ( 56 ). Scanning electron microscopy (SEM) examination has shown that RP are made of a mixing of tubules with calcified walls and of tubules obstructed by CaP plugs ( 57 ). RP consists of CaP crystals mixed with an organic matrix that is rich in various proteins and lipids, and includes membrane-bound vesicles or exosomes, collagen fibers, as well as other components of the extracellular matrix ( 58 ). An increasing number of studies have suggested that RPs are the origin of renal stones ( 57 - 60 ). Winfree et al ( 61 ) clarified that kidney stones develop as an overgrowth on RP, which contains unique organic composition (fibrillar collagen) that can be differentiated from the stone overgrowth by specific autofluorescence signatures. Of note, a previous study using a murine mode of RP revealed that vitamin D supplementation and calcium intake could notably accelerate RP formation ( 60 ). However, the precise mechanisms of RP formation remain unclear.

Recently, studies indicated that long non-coding RNAs (lcnRNAs) H19 and MALAT1 mediated osteogenic differentiation of human renal interstitial fibroblasts (hRIFs) and participated in RP formation ( 62 - 64 ). lcnRNA H19 has been shown to be significantly upregulated in RP, which can promote the osteogenic differentiation of hRIFs by activating Wnt/β-catenin signaling ( 63 ). lcnRNA H19 can also serve as a facilitator in the process of CaOx nephrocalcinosis-induced oxidative stress and renal tubular epithelial cell injury through the interaction with miR-216b and exerts its effect via the HMGB1/TLR4/NF-κB signaling pathway ( 64 ). lcnRNA MALAT1 can function as a competing endogenous RNA (ceRNA) that sponges miR-320a-5p, upregulates Runx2 expression and thus promotes the osteogenic phenotype of hRIFs ( 62 ).

These studies provide novel insight into the pathogenesis of RP-mediated kidney stone disease, while further studies are urgently anticipated to explore the mechanisms of RP formation, as well as additional roles of RP in the context of stone formation.

4. Role of sex hormones in calcium oxalate nephrolithiasis

Statistical analyses have revealed that males have a higher incidence of CaOx nephrolithiasis than females at a ratio of 2-3:1 ( 4 , 65 ); however, the exact mechanism remain unclear. Previous studies have indicated that androgens increase and estrogens decrease urinary oxalate excretion, plasma oxalate concentration and kidney CaOx crystal deposition. Additionally, enhanced androgen signaling may be responsible for the association between sex and kidney stone formation ( 65 - 68 ). Androgen receptor (AR) signaling can directly upregulate hepatic glycolate oxidase ( 69 ) and kidney epithelial nicotinamide adenine dinucleotide phosphate oxidase (NAPDH), subunit p22-PHOX at the transcriptional level, so as to increase oxalate biosynthesis, ultimately leading to kidney stone formation ( 70 ). Peng et al ( 71 ) reported that testosterone contributes to nephrolithiasis development through the induction of renal tubular epithelial cells apoptosis and necrosis through HIF-1α/BNIP3 pathway. Changtong et al ( 72 ) revealed that testosterone could promote kidney stone disease via the enhanced COM crystal-cell adhesion by the increased surface α-enolase. Zhu et al ( 73 ) demonstrated that AR can inhibit the recruitment of macrophages and suppress the COM crystals phagocytic ability of macrophages via the decrease of the colony-stimulating factor 1 (CSF-1) signals, through miR-185-5p upregulation. These findings suggest that androgen receptor signaling may be a key player in the development of nephrolithiasis ( Fig. 2 ).

Role of sex hormones in calcium oxalate nephrolithiasis. The AR signaling could induce TECs apoptosis and necrosis and kidney tubular injury, promote COM crystallization and oxalate biosynthesis; however, macrophage recruitment and crystal phagocytosis are inhibited. Conversely, ER signaling can reduce ROS-mediated kidney tubular injury and COM crystallization. COM, calcium oxalate monohydrate; AR, androgen receptor; ER, estrogen receptor; ROS, reactive oxygen species.

Theoretically, AR may be a new potential target and can be evaluated for novel therapeutics for the suppression of kidney stone formation. The 5α-reductase inhibitor, finasteride, has been reported to abolish the promoting effect of testosterone on COM crystallization ( 74 ). Another newly developed AR degradation enhancer, dimethylcurcumin (ASC-J9), has been reported to suppress oxalate crystal formation via the modulation of oxalate biosynthesis and reactive oxygen species (ROS)-induced kidney tubular epithelial cell injury in a rat model ( 73 ). Reversely, estrogen may serve as a protective factor against kidney stone formation. An in vitro study demonstrated that estrogen led to changes in the cellular proteome of [Madin darby canine kidney (MDCK)] renal tubular cells that led to the decreased CaOx crystal receptor surface expression (annexin A1 and α-enolase), reduced intracellular ATP, and enhanced cell proliferation and renal tubular cell tissue healing ( 75 ). There is evidence to suggest that estrogen receptor β (ERβ) can suppress oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) through the direct binding to the estrogen response elements (EREs) on the NOX2 5′ promoter ( 76 ), which exerts protective effects on renal CaOx crystal deposition.

All these findings may partly explain why a higher incidence of nephrolithiasis is encounter in males than in females. Targeting AR may be developed as a potential therapy for CaOx crystal-related kidney stone disease. However, these studies were performed in vitro and in vivo , using only cell lines or animal models. Further validation and clinical studies are required. Finasteride and ASC-J9 have been demonstrated to suppress a number of AR-mediated diseases, including prostate cancer ( 77 , 78 ), liver cancer and spinal and bulbar muscular atrophy neuron disease ( 79 ). However, additional future studies are necessary before the clinical application of finasteride and ASC-J9 in kidney stone prevention, considering the side-effects, including sexual dysfunction ( 80 ).

5. Role of the microbiome in stone formation

Emerging evidence has indicated that microorganisms belonging to the human microbiome, including microorganisms of the kidney and urinary tract, are likely to have a profound effect on urological health, both positive and negative, due to their metabolic output and other contributions ( 81 ).

Urease-producing bacteria

Urease-producing bacteria, such as Proteus mirabilis, Klebsiella pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, Providentia stuartii, Serratia and Morganella morganii , are always associated with struvite stone formation and recurrence ( 82 , 83 ). The bacterial urease degrades urea and promotes ammonia and carbon dioxide formation, leading to urine alkalinization and phosphate salt formation ( Fig. 3 ).

Role of urease-producing bacteria in stone formation. The urease-producing bacteria split urea and promote the formation of ammonia and carbon dioxide, leading to kidney tubular injury and urine alkalinization and subsequent formation of phosphate salts.

Urinary acidification and urease inhibitors have been proposed and implemented for the prevention and/or dissolution of struvite stones and encrustations in patients with infection by urea-degrading bacteria; however, their long term use is limited due to their ineffectiveness and toxicity ( 84 ). Secondarily infected stones caused by non-urease-producing bacteria, including Escherichia coli and Enterococcus spp., have also been described ( 85 , 86 ). However, whether kidney stones form and become secondarily infected or result from a nidus of infection that propagates stone formation remains largely unclear.

Nanobacteria (NB)

NB have been isolated from kidney stones for >30 years ( 87 - 89 ); however, the nature and the mechanisms involved remain obscure. Ansari et al ( 90 ) demonstrated that the size of cultured NB varies between 60 and 160 nm, and that they could infect patients with apatite kidney stone. Kajander et al ( 91 ) indicated that NB can adapt to growing in plain DMEM or RPMI-1640, through self-proliferation. In the study by Ciftçioglu et al ( 92 ), it was demonstrated that 70 out of 72 (97.2%) kidney stones contained NB. The presence of NB was independent of the stone type, although apatite-based kidney stones presented the highest immunopositivity ( 91 ). NB are considered to play roles in calcium nucleation, as they can produce sufficient calcium apatite in their cell walls to initiate pathologic calcifications and stone formation ( 93 - 95 ). This evidence is strongly in favor of the suggestion that NB are living organisms.

However, an increasing number of studies have indicated that NB, also termed 'Calcifying nanoparticles (CNPs)', 'nanobacteria-like particles' or 'Nanobes', are merely mineral protein nanoparticles with biomimetic functions ( 88 , 89 ). Although the definition and nature of these nanoparticles remains controversial ( 96 ), their roles in kidney stone diseases has been widely reported. CNPs have been identified in RPs and have been proven to be cytotoxic to 3T6 fibroblasts and HK-2 cells in vitro ( 89 ), which contributes to the renal tubular epithelial cell injury linked to kidney stone formation. Hong et al ( 97 ) demonstrated that catalase (CAT) and malonaldehyde (MDA) levels were significantly higher in CNP-treated HK-2 cells than the HK-2 control group, suggesting that CNPs may induce lipid peroxidation and result in damaging HK-2 cells. Wu et al ( 89 ) demonstrated that the CNPs may: Induce ROS production through JNK activation; decrease mitochondrial membrane potential and promote cell apoptosis through the downregulation of Bcl-2 expression and the upregulation of Bax expression; lead to autophagy through the upregulation of microtubule-associated proteins 1A/1B light chain 3B (LC3-II) and Beclin-1 expression ( Fig. 4 ).

Role of nanobacteria in stone formation. The nanobacteria may induce ROS production through the JNK/p-JNK signaling induction, may decrease mitochondrial membrane potential and promote cell apoptosis through the downregulation of Bcl-2 expression and the upregulation of Bax expression. Additionally, nanobacteria may lead to autophagy through the upregulation of LC3-II and Beclin-1 expression. ROS, reactive oxygen species; LC3-II, microtubule-associated proteins 1A/1B light chain 3B.

According to currently available findings in the literature, NB are localized in high concentrations in kidneys, excreted in urine, are isolated from RPs and the majority of renal stones, and play the role of the initiator, by favoring nucleation and crystal formation. Continued investigations are required, in order to solve the controversy of whether NB are living or non-living, as well as the mechanisms through which NB induce calcification and stone formation.

Intestinal microbiota

The intestinal microbiome, which has been a recent area of wide interest, has been reported to play a role in both the pathogenesis and prevention of kidney stone disease ( 87 , 98 - 100 ). Oxalobacter formigenes is the most well-studied Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract and has potential probiotic characteristics for the prevention of CaOx kidney stone formation.

In a pilot study, Stern et al ( 101 ) investigated the distinct differences in the gut microbiome of nephrolithiasis patients, as compared with patients without kidney stone formation. Their results demonstrated that the genus Bacteroides were 3.4-fold more abundant in the kidney stone group, while the genus Prevotella were 2.8-fold more abundant in the non-stone control group. A 24 h urine analysis revealed that the genus Eubacterium was inversely associated with oxalate levels and the genus Escherichia trended to an inverse correlation with citrate level ( 101 ). However, the potential causative role of pre-existing dysbiosis of gut microbiome in kidney stone disease is still unclear, and the association of urinary oxalate excretion and oxalate-degrading bacteria abundances remain limited ( 87 , 98 , 102 , 103 ).

Both absorptive and secretory pathways for oxalate have been identified in the proximal and distal segments of the colon, regulated by neuro-hormones that direct net oxalate level. Thus, it has been suggested that intestinal tract participates significantly in oxalate balance and subsequent oxalate homeostasis ( 104 - 106 ). The intestinal tract is also where oxalate-degrading bacteria tend to reside, particularly Oxalobacter formigenes , which requires a strict anaerobic environment to survive. One hypothesis for the role of the microbiome in the prevention of kidney stone has been that specific functional bacteria, such as the oxalate-degrading bacteria (such as Oxalobacter formigenes , Bifidobacterium sp. Porphyromonas gingivalis and Bacillus sp.) in human gut and intestinal tract, which use oxalate as their carbon energy source and thrive in the presence of the oxalate anion, exhibit growth inhibition in the CaOx crystallization in the kidney ( 102 , 107 , 108 ) ( Fig. 5 ).

Role of oxalate-degrading bacteria in stone formation. Oxalate-degrading bacteria use oxalate as a carbon energy source and thrive in the presence of the oxalate anion, reduce urinary oxalate level and exhibit growth inhibition in the calcium oxalate crystallization in the kidney.

The activity of oxalate-degrading bacteria mediates extra-renal elimination of oxalate in the intestines and has a significantly impact on the homeostatic levels of oxalate in plasma and urine ( 109 ). This activity exhibits a strong association with the occurrence of CaOx stone formation.

6. Immune response to urinary crystals

Macrophage accumulation and macrophage-related inflammation or anti-inflammation is the main immune response alteration observed in kidney stone disease, which has been widely reported to play a crucial role in renal CaOx crystal formation ( 110 ).

Firstly, the recruited macrophages could promote the development of COM crystals via the interaction of CD44 with OPN and fibronectin (FN) ( 111 ), which are upregulated in renal tubular cells induced by crystals. Secondly, macrophages have been evidenced to secrete various mediators via classical secretory pathways that cause renal interstitial inflammation ( 112 , 113 ), particularly macrophage inhibitory protein-1, monocyte chemoattractant protein-1 and interleukin-8 (IL-8) ( 112 ). These chemokines consequently enhance the recruitment of various immune cells, including monocytes, macrophages, neutrophils, dendritic cells and T-cells into the inflammatory locale ( 114 , 115 ). Several studies have demonstrated that macrophage-derived exosomes following COM exposure are involved in kidney stone pathogenesis ( 112 , 113 , 116 ). A set of proteins in COM-treated macrophage exosomes were previously identified as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation and cell migration ( 112 ). Additionally, infiltrated monocytes could differentiate into different macrophage subtypes with a wide range of clinical manifestations, presentations and histological phenotypes ( 110 , 117 ), display protective or pathogenic activities in kidney stone development ( 110 ).

Increasing evidence has revealed that M1/M2-macrophage differentiation plays an important role in renal CaOx crystal formation ( 111 , 115 , 118 - 120 ). However, whether M1 macrophage-mediated inflammation that contributes to stone formation will initiate stone promoters and reduce stone inhibitors remains controversial. Khan et al ( 58 ) demonstrated that M1 macrophages could cause acute tissue injury, which was associated with crystal deposition and RP formation. Conversely, Taguchi et al ( 121 ) concluded that there was no association between renal dysfunction and increased crystal deposition, based on their observation that no changes were observed in urinary variables in lipopolysaccharide (LPS)-induced M1 macrophage-mediated acute renal injury. M2 anti-inflammatory macrophages can phagocytize and degrade CaOx kidney stone fragments through a clathrin-dependent mechanism ( 110 , 113 , 115 , 120 , 121 ) ( Fig. 6 ).

Immune response to urinary crystals. Macrophage accumulation and macrophage-related inflammation or anti-inflammation is the main immune response alteration observed as a result of kidney stone formation. M1 macrophages are important effectors of CaOx stone formation, while M2 macrophages could prevent CaOx inflammatory damage through crystal phagocytosis. CaOx, calcium oxalate.

Given the critical role of immune-response in CaOx crystal formation and development, the immunotherapy approach has been proposed to prevent stone recurrences in certain individuals through the modulation of the immune response, in order to degrade CaOx crystals and thus prevent stones from developing ( 122 ). However, investigations into immunotherapeutic targets for kidney stone disease are urgently required.

7. Conclusion and future perspectives

In the present review article, emerging concepts of mechanisms contributing to stone formation were summarized, by reviewing novel insight into kidney stone disease related-metabolic risk factors, receptors, promoters and inhibitors, through the examination of the roles of immune-response, microbiome and sex hormones in stone formation and development. The pathophysiology of kidney stone disease cannot be completely explained by crystallization processes alone. However, due to current limitations in research, there are still some research areas in kidney stone formation that remain poorly understood, and were not been discussed herein. Future comprehensive studies are mandatory to further elucidate the mechanisms of the microbiome and immune response in kidney stone formation, in order to develop novel prophylactic and therapeutic approaches.

Acknowledgments

Funding statement.

The present study was supported by the National Natural Science Foundation of China (grant no. 81802566), and Shenzhen Science and Technology Program (Basic Research Project, grant no. JCYJ20180228163919346).

Availability of data and materials

Authors' contributions.

ZW and YZ prepared and drafted the manuscript. ZW obtained funding for the study, and drafted and revised the manuscript. QD, JZ and HL assisted in obtaining data for the review article, drafted the manuscript and provided critical revision of the manuscript for intellectual content. ZW and HL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

Patient consent for publication, competing interests.

The authors declare that they have no competing interests.

When did your kidney stone start growing? ANSTO scientist carbon dated his to find out

ABC Science

Topic: Weird and Wonderful

Research into kidney stones can help scientists understand more about how they form.   ( Supplied: Vladimir Levchenko/ANSTO )

In 2011, Vladimir Levchenko experienced the searing pain about six per cent of us will experience — a kidney stone beginning its excruciating trek down the urinary tract.

A trip in an ambulance to the hospital led to him being wheeled into an operating theatre to have his kidney stone removed. 

In between the bouts of pain , Dr Levchenko, who is a research scientist at Australian Nuclear Science and Technology Organisation (ANSTO), began wondering when his problem began.

He was curious to see if he could work out how long ago his stone had started forming.  

And as an expert in carbon dating, he began asking questions about his stone.

When the doctor said it was made of a carbon compound called oxalate, "that clicked in my brain, I can [date] that," Dr Levchenko recalls. 

He'd recently been working on dating oxalates from Aboriginal rock art.

"I asked, 'Could you please save it for me?' And he did."

This fateful moment lead to multiple papers, and a deeper understanding of how kidney stones grow. But Dr Levchenko thinks there's plenty left to do. 

How kidney stones grow

Kidney stones are formed from calcium salts produced by our urine. 

While most of this is removed from the body when we go to the toilet, occasionally the salt can become a tiny crystal that grows over time.

Urology surgeon and kidney stone expert Gregory Jack's first interaction with a patient is usually when they show up at the emergency room with a kidney stone in their urinary tract. 

"You've got something too big being pushed through a tube that's too small. Almost like a golf ball through a garden hose," he says. 

"They've been unaware of it, and they're quite traumatised by the pain. And I won't have any old scans or any old records."

One of Dr Jack's patients had an 80mm kidney stone which required surgical removal.  ( Supplied: Gregory Jack )

Once someone has been diagnosed with kidney stones they are normally tracked over years or decades using X-ray or ultrasound, but finding the first stones can be a surprise for both  the patient and the doctor. 

If the stones are small, patients will pass them through their urinary tract, but larger stones are removed via surgery, or broken up with ultrasound.  

Once the stone has exited the body it's possible to track how old it is  — approximately — by understanding how it formed and looking at its "growth rings" as more layers of calcium salts are added.

Under 1000x magnification, the crystalline structure of kidney stones become clear.  ( Supplied: Vladimir Levchenko/ANSTO )

"Over years, decades or even a person's lifetime, the stone will slowly grow," Dr Jack says. 

Similar to a tree, "we crack open the stone, and often we'll see 100 different rings inside."

Fast kidney stones with extremely thick rings can grow in a few months, while most take years or decades. 

"Some years the rings are quite fat, meaning the stone grew quite quickly. Other years, the rings may be quite thin, meaning the patient has having a good year."

But they're not quite as accurate to years as tree rings, meaning they don't provide an exact date, and don't give doctors or patients information on how the stones may have started.

This means doctors aren't able to provide information to patients about how long it could take for another stone to form and pass.

Carbon dating using the bomb pulse

Once Dr Levchenko had recovered from surgery, he took his six millimetre kidney stone, and removed a tiny sample of the stone's core, middle and outside. 

"The biggest difficulty was just to find out where it started growing. It's not necessarily symmetrical," he says.  

These tiny samples were then analysed by a giant machine called an accelerator mass spectrometer.

This process measures the amount of a radioactive isotope called carbon-14 inside the kidney stone samples to determine their age.

The technique is also used to date ancient bones, plants or anything else that's absorbed carbon over its lifetime.

When the organism dies, fresh carbon stops being exchanged with the environment, and the carbon-14 begins to steadily decay, allowing scientists to estimate the time of death.

And while specimens under 60,000 years old can be dated down to a few hundred or thousand year time frame, specimens after 1950 — such as Dr Levchenko's kidney stones — can be dated much more accurately.

Dr Levchenko wants to carbon date more kidney stones.  ( Supplied )

That's because of something called the "bomb pulse" — when carbon-14 in the atmosphere doubled as a result of nuclear bomb tests in the 50s and 60s.

This increase in carbon-14 allows researchers to date samples precisely, sometimes all the way down to the month. 

Being able to use this bomb pulse to accurately date samples will only last until about 2030, when carbon-14 levels return to baseline. 

This pulse allowed Dr Levchenko to date the kidney stone extremely accurately from the outer sample to the core. 

The outer edge sample correlates to when the stone was removed. Then working backwards to the core, he discovered his stone had been slowly growing inside his kidney for 17.6 years. 

This finding led him to undertake even more research with a group in the Netherlands, with two more stones sent over from two separate patients, which also provided some interesting results.

Those two stones, which were similar in size, had completely different growth rates — one had grown over the past 23 years, while the other had grown in just seven years. 

Dr Levchenko's kidney stone removal in 2011 started the entire process.  ( Supplied: Vladimir Levchenko )

"Knowing the growth rate is helpful, because it does help counsel the patient. If it took 15 years to grow one, you can extrapolate 15 years for the second," Dr Jack says. 

But, he adds, "knowing the timing is fun, but it probably doesn't help the prevention as much as knowing the cause".

How to prevent kidney stones

When a kidney stone is passed from the body, normally a number of tests are done to test the stone, to try to work out what caused it. 

"The first thing we'll do is we'll send it to the lab to see what what type of stone it is," Dr Jack says. 

"The vast majority will be a calcium stone, but there'll be other types … knowing the type will help us determine a little bit of what's going on."

Dr Jack suggests drinking more water to prevent kidney stones.  ( Supplied )

Unfortunately, Dr Jack has seen plenty of research trends come and go when it comes to how to prevent kidney stones. 

"Our poor patients. A decade ago they were told to not have calcium. And then we realised we got that all wrong.

"So then they were told, don't have oxalates [found in some foods such as green leafy vegetables]. And then we found out we got that wrong too," he says. 

"The diet stuff just comes in fads, and then all of a sudden, everybody cuts out spinach and kale."

Now there are three things Dr Jack advises almost all his patients:

• drink more water
• have less salt
• eat less animal protein

The rest of the advice is normally tailored to the individual. 

"We can do fancy urine tests and measure out in someone's urine a number of different electrolytes and see what levels are off in that individual," he says. 

"I see all of these patients every day, and they all want to know what caused [their stone]."

'Whatever comes naturally'

Dr Levchenko has since had one more, smaller kidney stone, but this one was seen on an X-ray screen, and removed before it became a problem. 

But the original kidney stone dating, and subsequent publication of his research brought him in contact with kidney stone researchers around the world.

Despite the research he's already done, Dr Levchenko believes that there's plenty more to be done in this space. 

According to him, further research may help scientists understand more about how diet and lifestyle affect stone growth.

The kidney stones used in Dr Levchenko's research need to be cut in half to find the centre.     ( Supplied: Vladimir Levchenko/ANSTO )

While he had plans to work with the Dutch researchers to investigate more stones, COVID caused the plans to be shelved. 

"When the pandemic subsided, the research structure, organisation and funding changed too," Dr Levchenko says. 

"In Australia, there's no active groups in this field … hopefully, it will change."

"When I first started getting in touch with kidney stone researchers, they didn't understand what I was suggesting," he says. 

They assumed he wanted to feed their patients radioactive isotopes.  

"I said, 'No, they eat them anyway. It comes in our diet,'" he laughs. 

"I'll measure whatever comes naturally."

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New insight into oxidative stress and inflammatory responses to kidney stones: Potential therapeutic strategies with natural active ingredients

Affiliations.

• 1 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, China.
• 2 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, China; National-Local Joint. Engineering Research Center of Entomoceutics, Dali, Yunnan, China.
• 3 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, China; National-Local Joint. Engineering Research Center of Entomoceutics, Dali, Yunnan, China. Electronic address: [email protected].
• 4 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, China; National-Local Joint. Engineering Research Center of Entomoceutics, Dali, Yunnan, China. Electronic address: [email protected].
• PMID: 39243436
• DOI: 10.1016/j.biopha.2024.117333

Kidney stones, a prevalent urological disorder, are closely associated with oxidative stress (OS) and the inflammatory response. Recent research in the field of kidney stone treatment has indicated the potential of natural active ingredients to modulate OS targets and the inflammatory response in kidney stones. Oxidative stress can occur through various pathways, increasing the risk of stone formation, while the inflammatory response generated during kidney stone formation further exacerbates OS, forming a detrimental cycle. Both antioxidant systems related to OS and inflammatory mediators associated with inflammation play roles in the pathogenesis of kidney stones. Natural active ingredients, abundant in resources and possessing antioxidative and anti-inflammatory properties, have the ability to decrease the risk of stone formation and improve prognosis by reducing OS and suppressing pro-inflammatory cytokine expression or pathways. Currently, numerous developed natural active ingredients have been clinically applied and demonstrated satisfactory therapeutic efficacy. This review aims to provide novel insights into OS and inflammation targets in kidney stones as well as summarize research progress on potential therapeutic strategies involving natural active ingredients. Future studies should delve deeper into exploring efficacy and mechanisms of action of diverse natural active ingredients, proposing innovative treatment strategies for kidney stones, and continuously uncovering their potential applications.

Keywords: inflammatory response; kidney stones; natural active ingredients; oxidative stress.

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Immunosuppressants (Anti-rejection Medicines)

Table of contents, about immunosuppressants (anti-rejection medicines), how they work, effectiveness, side effects and monitoring, tips for taking your anti-rection medications, paying for anti-rejection medicines after transplant, questions to ask, more resources.

Your immune system’s job is to fight anything that is “foreign” to your body. It looks for things that do not belong, like bacteria and viruses (germs). For people who have received a kidney transplant, your immune system will also try to fight, or reject , your new kidney since it isn’t like the rest of your body. So, anti–rejection (immunosuppressant) medications are needed to increase your chances of keeping your new kidney healthy. 

Anti-rejection medicines are for life – your new kidney is depending on them! Stopping, missing, or skipping these medicines will very likely cause rejection, either right away or over time. 

Anti-rejection medicines are very important for people who have received a kidney transplant. They help lower (suppress) your body’s natural response to fight your new kidney. 

Immunosuppressants are what protect your new kidney from your own body’s natural attack response. There are many types of anti-rejection medicines, and each works in a slightly different way. The goal with these medicines is to find the right balance between stopping your immune system from fighting your new kidney while keeping it strong enough to fight other germs and prevent serious infections. So, most people who have received a kidney transplant will need a combination of anti-rejection medicines to help achieve this balance.

Everyone has a different level of risk for rejecting their new kidney. So, your transplant team will design a medication regimen (number of medicines and their doses) specifically for you and your situation.

After Transplant: Medications and Possibility of Rejection

A free, self-paced online program about what to expect in the first year after transplant and beyond.

There are 3 groups of anti-rejection (immunosuppressant) medications:

• Induction medicines : – a strong anti-rejection medicine given intravenously (IV) before you receive your transplant (usually in the operating room) and repeated one or more times in the days after your transplant surgery. This medicine helps get your body’s immune system ready to accept the new kidney. Your transplant team will determine the specific medicine and number of doses you need based on your personal risk for kidney rejection. 
• Maintenance medicines : anti-rejection medicines you will take for as long as you have your transplanted kidney. These medicines are started shortly after your surgery (while you are still in the hospital) and then you will be responsible for managing them long-term after your transplant. More information about these medicines is shared below.
• Rejection treatments : medicines which are used if your body starts to reject your kidney, also called a rejection episode. If you have symptoms of rejection, call your transplant team right away as this can be a medical emergency. 

Common maintenance immunosuppressants (anti-rejection medicines)

The list below is focused on the most common “maintenance medicines”. These are the medicines that need to be taken every day to help you prevent the rejection of your kidney transplant. Most patients will need a combination of medicines from this list to get the most benefit of keeping your new kidney healthy.

Calcineurin (kal-suh-NUR-uhn) Inhibitors, also known as CNIs

• Examples: tacrolimus (Prograf, Astagraf XL, Envarsus XR); cyclosporine (Sandimmune); modified cyclosporine (Neoral, Gengraf)
• Usually taken twice daily (dosed 12 hours apart) unless it is an extended-release version (like Astagraf XL or Envarsus XR) which can be taken once daily in the morning 
• Do not eat grapefruit or drink grapefruit juice if taking a CNI. It can make your medicine stronger and cause very serious side effects.

Glucocorticoids (gloo-koh-KOR-tuh-koydz), also known as steroids

• Examples: prednisone; methylprednisone (Medrol, Solu-Medrol) 
• Usually taken once daily with a meal (to lower risk of upset stomach). 
• It is best taken in the morning since it may lead to trouble falling asleep (especially at doses of 40 mg per day or higher). 
• It can cause many other side effects – each person has a different experience. Talk to your transplant team if you are having trouble tolerating your prednisone. Side effects are often less common or bothersome at lower doses.

Antimetabolites

• Examples: mycophenolate mofetil (often abbreviated MMF) (Cellcept, Myfenax); mycophenolic acid (often abbreviated MPA or EC-MPS) (Myfortic); azathioprine (Imuran)
• All forms of mycophenolate increase the risk of pregnancy loss and birth defects. Talk to your transplant team if you are pregnant or planning to become pregnant.
• Both mycophenolate products are taken twice daily (dosed 12 hours apart).
• Azathioprine is less commonly used in the United States. It can be considered for people who are pregnant or planning to become pregnant.

Other medicines

• Examples: sirolimus (Rapamune); everolimus (Afinitor, Zortress); belatacept (Nulojix)
• These medicines are usually not part of the regular treatment plan that starts right after your transplant. Instead, they offer other options for people who are having side effects or other problems with CNIs listed above. 
• Sirolimus is taken once daily by mouth. Everolimus is taken twice daily by mouth. Belatacept is an intravenous (IV) infusion given every 2 weeks for the first few doses, then every 4 weeks.

There are some foods that affect these medications and make them stronger or weaker, such as grapefruit and grapefruit juice. Read more about NKF's Nutrition Coach .

These medicines have been proven to help stop the body from rejecting the new kidney for many years after transplant surgery. To increase your chances of success, you should always take your anti-rejection medications as prescribed by your transplant doctor (or another member of your transplant team). This still holds true no matter how you feel or if you think your transplanted kidney is working well enough to no longer need them. 

These medicines are for life – your new kidney is depending on them! Stopping, missing, or skipping these medicines will very likely cause rejection, either right away or over time. Kidney rejection is hard to diagnose in its early stages. Rejection often cannot be stopped once it starts and results in the loss of the transplanted kidney.

Keep in mind that your anti-rejection medicines may change over time – doses may change, new medicines may be added, and/or some medicines may be stopped. It’s important to check in regularly with your transplant team and always follow your most recently updated medication list.

Anti-rejection (immunosuppressant) medicines have several possible side effects. These are usually manageable for most patients and often get better over time. Some of the most common side effects of anti-rejection (immunosuppressant) medications include:

• High blood pressure
• High cholesterol
• An increased chance of having infections
• Gastrointestinal (stomach/digestive) side effects
• Increased risk of some forms of cancer

To help with side effects, you will need regular blood draw labs to check how much medicine is in your blood. If there is too much medicine, your side effects may be worse. If there isn’t enough medicine, your kidney may not be protected enough. When you first get your transplant , you will have blood draws more often. As time goes by, you will not need them as often. Even if your blood draw labs say your medicine levels are in the goal ranges, tell your transplant team about any side effects or symptoms you are feeling. Your healthcare professional may be able to change your doses and/or switch to a different medicine.

Living with daily medicines often means creating new habits so you can remember to take them in a way that fits into your routine. Talk to your transplant team if you are having trouble sticking to your medicine schedule. Some common barriers and potential solutions shared by patients include:

If a healthcare professional outside of your transplant team gives you a prescription for a new medicine, let your transplant team know right away before taking it. The same is true for any over-the-counter medicines, herbal supplements, or vitamins you are planning to take. Many medicines and supplements can interfere with your anti-rejection medicines. The combinations can sometimes stop your anti-rejection medicines from working or make the medicine level in your blood go too high and cause side effects. To learn more about how foods and supplements can affect your anti-rejection medicines, visit Diet after Kidney Transplant .

Anti-rejection medicines can be expensive, but there are a lot of ways to get help paying for them. It is very important to always take your medicines as prescribed. Don’t lower your doses or stretch out doses to try and save money. This is extremely dangerous and should not be done because it can hurt your kidney and/or cause rejection. Call your transplant center’s financial coordinators and/or social workers if you are having trouble or are worried about paying for your medication. If you have Medicare, you can also reach out to a certified Medicare counselor in your state.

No insurance

If you meet the following criteria:

• had your kidney transplant at a Medicare-approved facility in the United States,
• do not have Medicaid, and
• do not have any other form of insurance, 

you may be eligible for Medicare Part B-ID to cover only your immunosuppressants. Even if you are under 65 and it has been more than three years since your transplant, lifetime Medicare coverage for immunosuppressants is available. 

Other prescription assistance programs

Some companies offer prescription assistance programs for patients on their medications to those who qualify. Visit the NKF Prescription Discount and Assistance Resources page for a list of assistance programs available for medicines that people with kidney disease and/or kidney transplant may need.

• What maintenance medicines does your transplant center use after transplant?
• Will any of these anti-rejection medicines interact with my other medicines and/or health conditions?
• If you have a new problem bothering you: Could my medicines be causing this? 
• If you cannot tolerate your medicine’s side effects: What are my other options for medicine?
• Who can I call if I am having trouble paying for my medication? Does your center have access to any programs that can help?
• How often will you want me to have bloodwork to check my medicine levels? How will that change over time after my transplant?
• Will you keep following up with me about my medicines after one year? If not, how do you help patients transition back to another healthcare professional (like my regular nephrologist)?
• Who should I contact if I plan to become pregnant (or unexpectedly become pregnant) in the future?
• NKF Cares : a patient hotline to answer any questions you may have about kidney disease, transplant, or living donation. Call toll-free at 855.NKF.CARES (855.653.2273) or email [email protected] .

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