architectural case study of hospital in india

Symbiosis University Hospital and Research Centre | IMK Architects

Information

• Project Name: Symbiosis University Hospital and Research Centre
• Practice: IMK Architects
• Products: Wipro , Legero Lights , Alstone , Saint Globin , Nyati Engineers & Consultants Pvt Ltd. , Parryware , Cera , Weathercool
• Completion year: 2019
• Gross Built up Area: 41800 sqm
• Project Location: Pune
• Country: India
• Lead Architects/Designer: Rahul Kadri
• Design Team: Nithin Hosabettu (Design Director), Sahil Bipin Deshpande (Architect), Viraj Naralkar (Architect), Aakash Kumar Srivastav (Architect), Oshmi Sengupta (Architect),Pallavi Rai (Architect)
• Clients: Symbiosis Society
• Engineering: The Axis Structural Consultants, Pune
• Structural Consultants: The Axis Structural Consultants, Pune
• MEP Consultants: Radiant Consulting Engineers, Navi Mumbai
• Landscape Consultants: IMK Architects
• Photo Credits: Rajesh Vora
• Others: HVAC: Radiant Consulting Engineers, Navi Mumbai Lighting: IMK Architects & Radiant Consulting Engineers Façade: IMK Architects

Excerpt: Symbiosis University Hospital and Research Centre is an architectural project designed by IMK Architects in Pune, India. Sitting along a slope, the building is strategically positioned to minimize the cut-and-fill of the hill site. Planned as a robust curve along the contours of the land, it forms the project’s façade. Imbibing the client brief of ‘grandeur’ being a key element, two significant and symbolic entrances have been designed, distinct in approach to cater to the client brief of unique identities for the hospital and the academic block.

Project Description

[Text as submitted by architect] Established on the lower slopes of a hill, amidst the sprawling 40 acres land of Pune’s renowned educational institute Symbiosis, SUHRC has been developed on a forested hill, in a discrete and quiet location. Envisaged as a Multi-Specialty Hospital to provide excellent health care facilities and a State of the art – Centre that would enhance Skill development in the Field of Medicine, the development envisions to educate and empower medical students. Conceptualized to cater to the needs of all the stakeholders, the hospital caters to the nearby population of Pune and its neighboring areas, while providing Tele-Medicine services to ensure outreach services to peripheral, far-flung and access-compromised settlements. Amidst today’s context, currently, the hospital is being used for Government welfare as COVID 19 hospital.

Sitting along a slope, the building is strategically positioned to minimize the cut-and-fill of the hill site. Planned as a robust curve along the contours of the land, it forms the façade of the project. Imbibing the client brief of ‘grandeur’ being a key element, two significant and symbolic entrances have been designed, distinct in approach to cater to the client brief of unique identities for the hospital and the academic block. While the entry to the hospital is welcoming, peaceful, it also provides a sense of grandeur along with a structure that expresses Solidarity, resonating care, and shelter for the patients in distress. A large open-to-sky courtyard separates the Centre from the hospital. The entrances for both these blocks lie on either side of the building, making them seem like two completely different entities, providing the students with different access as well as a space for them for relaxation and academic purposes.

The entrance for the Skill Centre draws inspiration from the stainless steel surgical instruments used in hospitals. A mammoth silver steel bird, with wings wide open, welcomes the visitor into the building. Supported by steel pipes, a futuristic roof under the sun beaming brightly, is symbolic of a contemporary architectural response. The roof sits above the large semi-circular staircase that leads the visitor to the entrance. In contrast, the response to the other block is humbler. Split into two entries, where one is for casualties and the other for regular populous, the base of the entrance is lifted to be in line with the interiors. Above this large entrance, a slightly curved roof is designed, shading the entrance and making it possible for people to wait outside too. The tip of the entrance is stretched upwards, thus letting in more light to create a deeper canopy so that at least two lanes of vehicles could be parked along the length of the building under it. The canopy was stretched to the complete width of the building and gave it a smooth curvilinear shape in the front, which mellows down the impact of the sheer size of this structure. A balance between light and shade has been achieved with smaller skylights within the roof, and a larger opening towards the upward bending tip. The upper surface of this canopy was converted to a terrace garden, such that even the single bed patients would be treated to a biophilic space, which would promote healing. Two large courtyards in the building create buffer zones that help in healing patients, bring in ample light, and are overlooked by wardrooms and the Out-Patient Department. The OPD has no air-conditioning but allows for fresh, natural air while ensuring sufficient ventilation.

All departments and spaces of the hospital are designed such to bring in daylight and natural ventilation. Even areas like OPD, waiting have courtyards on both sides and are naturally ventilated. Similarly, at all levels, there is a 3m wide corridor that abuts the central courtyard, which lets in natural light and ventilation, thereby reducing the AC load and power consumption for these areas. The courtyards act as spaces for healing, for the congregation while reducing cross-infections. The terrace gardens are landscaped with flowering trees and plants to create a soothing effect for the patients as well as the accompanying caretakers. The main central courtyard transforms the space around it, unlike any regular hospitals, which are much mundane, completely air-conditioned spaces without any daylight and natural ventilation. Keeping sterility in mind, the courtyard is non-accessible, full of plants and small trees, etc. to avoid the risk of contamination and maintenance. The accessible spaces in the courtyard are paved with tiles and stones that are maintenance-free. The main central courtyard not only brings in the above features but also makes the space aesthetically pleasing, soothing to the eye creating a calm oasis. The space is completely transformed, unlike any regular hospitals, which are much mundane, completely air-conditioned spaces without any daylight & natural ventilation in significant areas. This also helped in simplifying the way-finding in the building, which otherwise in other hospital projects is a complicated affair for the users adding to their trauma in searching spaces/ departments within the structure.

This 216 Bedded Hospital provides state of the art 5 Operation Theatres, equally well equipped 22 ICU units. The Radiology department offers MRI, CT, X-ray, Fluoroscopy, BMD, and other scans. A dedicated Cardiology department with Cath Lab facility, Kidney dialysis with nine beds, separate Gynaecology Department with an independent OT Facility. Functionally, the building comprises of four sections; three of them belong to the hospital and the last one being the Skill Centre. Every section has been planned and conceptualized for its functionality- driven design and a distinct formal response as a result. The three blocks of the hospital, namely, the general hospital block, the procedure block, and the multi-specialty block, all have been planned with keeping in mind the ease of functionality and avoiding criss-cross movement. Amongst the 900 beds in the general hospital block, 600 beds are for free patients and procedures, which are all taken care of and treated by the medical college students. This block has been connected to the procedure block, with services running along one side of the corridor. At the same time, the departments are situated on the other, allowing for ease of access without causing any disturbances. Further, the procedure block is well segregated from the ward block to ensure privacy to every patient, while being shared as a standard procedure block by paid and free patients alike. This block is equipped with the latest medical technology being robotic Operation Theatres and surgical operations.

The hospital is planned across five levels; departments such as the OPD, casualty, radiology, MHC, etc. which require easy ground access and are frequented by more patients every day have been planned at the ground level. The first-floor compromises of General, Twin, and Single bed wards, most of which overlook the garden space. The critical areas such as OT’s, Pre-Op and Post Op, ICU’s Cath, etc. are planned on the 2nd floor, making it the sterile zone and thus are also segregated from other areas of the hospital. The 3rd floor, which was earlier planned for future expansion, was also converted to a ward floor as the client decided to get a DNB Accreditation, which required 200 + beds. All services are planned in the basement and lower ground level, including parking, stores, and other necessary hospital facilities such as morgue, medical gases, workshop engineering offices, garbage disposal, etc. The partly enclosed basement and LG levels are designed such that they use natural ventilation and daylight as much as possible. A 2.5 m wide ramp is also provided in the central courtyard, which will help patients to evacuate during a fire without being dependent on any mechanical systems.

Attention has been paid to construction details, where post-tensioned slabs are used to achieve flexibility, minimum beams, and larger spans that facilitate different size room arrangements and to allow for easy routing of ducts. The flexible grid is designed to synchronize the structural system at all levels. To enable a natural, original, and permanent finish on the building, which would be maintenance-free, brick was adopted as the material of choice for the double skin on the façade with deeper shading projections that would reduce heat gain. The resultant boxing forms were skewed, twisted, or tapered to achieve variations in shape to form a multi-faceted façade that reflects light in different tones in any part of the day. Creating dynamism through its texture, capturing the play of light and shadow each day, the façade looks different, complimenting every mood of the day. What is typically done in concrete, has been made possible in the brick and looks exclusive. Naturally compressed, sundried earthen bricks produced on-site, have been used for façade and masonry work and methods such as brick-boxing were incorporated to achieve efficiency, while reducing pollution. Together with exposed concrete, the skin and the façade flatter the green hills beyond.

Smaller details have been taken into account to ensure a calm and serene atmosphere that promotes healing while encouraging research and creating spaces that are easy to use and maintenance-free. Colour coding has been enabled for easy identification of the assortment of spaces and critical areas such as ICU’s are endowed with light colors of soothing shades to reduce anxiety. To maintain a warm and tranquil environment for patients, soft home-like colors cover the inner walls of the hospital. The ward rooms are designed with warmer and subtle hues of colors that are complemented with teak laminates. Varied temperatures and light with correct lux levels have been worked out for different areas, and the furniture has been customized for special and diverse needs. Acoustic materials in the ceilings of corridors and rooms reduce noise pollution and provide easy access to services. Encouraging way-finding, the nurse stations are highlighted with shades of warm yellow/orange to be identifiable from any side of the long corridor.

The Skill Centre is planned on the fourth and fifth floor with a separate entrance at the ground level. Being a part of the Symbiosis institution, the client brief called for a grand entrance that would be symbolic to the medical field, reflect Symbiosis legacy, and depict a futuristic approach. A grand entrance with steps ascending 8 m moves into the entrance porch. Shaped like the wings of a bird stretched to its extreme ends, the entrance is made of steel with an aluminium skin. Resting on a combination of steel and concrete Columns that give it a solid base and balance, the double-height entrance leads into a curvilinear café, which in turn connects to the Skill Centre designated vertical cores connecting to the 4th and 5th floor. The café gains ample daylight and natural ventilation as it has an enclosed courtyard on one side and stepped landscape on the other, thus creating a pleasant view for the users of the Café. The Skill Centre has four departments; Centre for health skills, School of Nursing, Institute of health science, and a School of Open and Distance learning. They share 9 classrooms with approximately 60- 90 students per class, a 300-seater auditorium, a library, meeting rooms, labs, changing areas, where all professionals such as Surgeons, Doctors, Nurses, and other allied fields.  All the departments are designed, planned, and implemented with one cohesive design vocabulary for medical professionals, with sufficient natural ventilation and daylight.

As multi-facetted angular walls create an orthogonal earthen tone on the façade, the landscape is designed as a free-flowing organic form, using plants of different colors, flower shrubs, and small trees. This creates a healing effect on the patients while acting as pleasant distractions for the patients’ relatives and hospital staff. The vast open space has been planned with approximately ____ number of trees of different species, shrubs, and plants with a vast retention pond at the lowermost level to facilitate zero discharge. The large retaining wall of exposed concrete also gets covered with climbers and plants, converting a blank mass of concrete to an aesthetically pleasing feature that adorns the approach to the hospital. Carefully and strategically planned, the building attempts to make gestures that are grand, yet local and responsive with attention to details such as the brick-art and the exposed concrete. Sitting comfortably on the fringe of the hill, the inner courtyards seem like a continuation of the hill, where the built form amalgamates with the site. Allowing nature to be a part of the hospital and integrating it as a comforting element for the patients, the hospital creates a space for recovery and rejuvenation.

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• Hospital Architecture

Vikram Hospital, Bengaluru, India

 A successful hospital design encompasses space utilization, hospitality issues, patient convenience and hi-tech infrastructure. Most of these require high degree of precision.  ZZ Architects has designed the hospital which fulfills all the requirements of a modern, contemporary and multi-specialty hospital. Vikram Hospital , located in Bengaluru , India , is designed to be among the few paperless hospitals in India .  This 285 bed hospital is spread over 8 floors.  The hospital is designed with the theme which is inspired by the ECG HEARTLINE GRAPH and so called “HEART BEATS THAT CONNECT”. The concept of signage was to merge it with the building elevations. Hence a visually strong graphic of heart beat pattern is printed on glass, demarcating the building as a medical facility. In this paperless hospital the information is directly transmitted from the patient’s palm pilot to a jaotech screen. The jaotech screen is also used by the patient for video conferencing with their relatives as well as the doctors. Paperwork is non existent as the billing process is also carried through these screens.

Visually, various design elements have been introduced into the hospital interiors. Each floor is color coded and the interiors reflect this in the smallest detail. From the colored bands in lift lobbies, to the colored ceiling graphics in the semi private rooms, this helps in identifying the floor for the users.

The architectural design of the hospital revolves around the theme of Natural Healing. The hospital is designed in such a way that natural light is available in maximum area wherever possible. Emphasis is given on creating green walls and plantation in the surroundings. Correct type of glass is used to reduce the heat and glare within the hospital.

Vikram hospital caters to both their staff and patient’s needs through the design. From the latest technology to the introduction of graphic visual elements, this hospital stands out amongst other hospitals in design and conceptual strengths.  

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hey can i have the detailed hey can i have the detailed case study of this hospital…asap and can u guys sent it to my email id….

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Apollo Reach Hospitals Modular Hospitals Improve Health Care Access Across India

The challenge.

Apollo Hospitals, one of the largest health care systems in Asia, asked HKS to design a modular building system for use on building sites in semi-urban and rural settings.

The Design Solution

The 140,000-square-foot Apollo Reach Hospital in Ayanambakkam is a 200-bed health care facility that serves as a test bed for the new modular system. HKS’ design uses 24-bed inpatient towers as the building’s core element with modular pods that house different services. When applying this building’s design in other locations, these pods can be rearranged to meet the site’s constraints and the needs of the community. The 120,000-square-foot (11,148 sm), 100-bed Apollo Reach Hospital in Nashik makes use of this concept by vertically stacking pods to meet the requirements of a smaller footprint.

The Design Impact

By creating a modular building system, the design, development and construction of new Apollo hospitals is simplified and accelerated, allowing the system to expand quality health care to underserved communities in India faster. The hospital in Ayanambakkam was designed as a prototype for site adaptation in 10 cities across semi-urban and rural India.

Project Features

• 24-bed inpatient tower units
• Emergency services
• Trauma unit
• General surgery
• Orthopedics
• Cardiovascular
• Outpatient clinics
• Blood donor center
• Neonatal ICU

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Rainbow Children’s Hospital – Banjara Hills

The Rainbow Children’s Hospital in Hyderabad offers a resource-efficient and comfortable environment for both patients seeking care and the medical staff working to save lives. The new facility is situated in the Banjara Hills neighborhood and is the second Rainbow Children’s Hospital to be EDGE-certified (the first is located in  Bengaluru ). The Banjara Hills facility provides comprehensive services for pediatric care, a perinatal unit, and other services for women with state-of-the-art infrastructure and the latest technologies.

The 205-bed hospital has many green features that conserve natural resources and improve operational performance. The solar panel heat pump hybrid system installed in the facility is projected to meet at least 60 percent of the building’s hot water demand, contributing to the reduction in energy. A black water treatment and recycling system is expected to reduce water use nearly in half. Embodied energy in materials will be reduced by 42 percent because of construction materials like autoclaved aerated concrete blocks for the hospital’s walls. These green measures were implemented at very little additional cost and the developer is expected to recover their investment in less than a year. The hospital is also estimated to save nearly $6,000 due to lower utility bills each month, allowing more money to be allocated toward patient care.

Since 1999, Rainbow Hospitals has provided excellent care to women and children. Rainbow constructed the first facilities dedicated to pediatric care in southern India and now has 11 facilities for women and children across the country. Rainbow Children’s Hospital – Banjara Hills has received final EDGE certification from GBCI.

Predicted Savings of EDGE Certification

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* Part of the energy efficiency percentage may be associated with virtual energy for comfort depending on the presence of heating and cooling systems. Note that virtual energy does not contribute savings to utility bills.

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Insulated roof, low-E coated glass, variable frequency drives in AHUs, variable speed drives pumps, energy-saving lighting and solar hot water collectors.

Low-flow showerheads and faucets, dual flush water closets, water-efficient urinals and a black water treatment and recycling system.

Autoclaved aerated concrete blocks for internal and external walls.

Road Number 2, Sri Nagar Colony Kamalapuri Colony, Banjara Hills Hyderabad, Telangana, India, 500034

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• Healthcare Center

Benziger Hospice Home / Srijit Srinivas Architects

• Curated by Hana Abdel
• Architects: Srijit Srinivas Architects
• Area Area of this architecture project Area:  1636 m²
• Year Completion year of this architecture project Year:  2020
• Photographs Photographs: Prasanth Mohan, Running Studios
• Manufacturers Brands with products used in this architecture project Manufacturers:   Saint-Gobain , Asian Paints , Blum , Burma Teak wood , Nitco Limited , Thovala , Weber
• Electrical Consultant : Rajesh Spectracon Engineering
• Civil : Robin , Judeson , Jolly
• Structural Consultant : Sujith , Rhiti
• Landscape : Rajagopal George
• Architect In Charge:  Srijit Srinivas
• Design Team:  Viji B, Sriya, Deepika, Remya Raveendran, Viji B., Sriya, Deepika
• Owner:  The Malabar Province of the Order of Discalced Carmelite
• Plumbing Consultant:  Jayaram
• Client's Project Office:  Fr. Joseph Mechery, Fr. Joseph Mechery
• Text:  Jeevan George
• City:  Thiruvananthapuram
• Country:  India

Text description provided by the architects. The Malabar Province of the Order of Discalced Carmelite (OCD) – affiliated to the Catholic Church, commissioned the ‘Benziger Hospice Home’ project in the South Indian city of Trivandrum with the vision of providing free accommodation for cancer patients visiting local hospitals. The project’s original brief was for five floors, which was reduced to three storeys encompassing 26 Patient Suites during project development.

Design Context – Challenges and Response. The site was oddly shaped – with a square front portion markedly tapering to the rear with an offshoot to the left housing an existing building earmarked for  future demolition. The design remit was to deliver a place of temporary stay for cancer patients which sensitively addresses their special needs and emotional vulnerabilities. The location in a crowded semi-urban setting, called for adequate privacy measures to screen neighboring residents’ views. 

Site Planning. An Ambulance entry was provided from the front main gate leading up to the entry ramp, which was girded by a veranda with inbuilt brick seating integrated with trough planters containing high oxygenating plants. The Service Gate to northern side allowed supply path to the kitchen plus maintenance access to the Plant room. The Ground Floor lobby opens to an enclosed northerly landscaped area for patients’relaxation. The Lobby with its cool, soothing micro-climate effected by its landscaped central courtyard - replete with brick seating and louvred screen walls permitting horizontal and vertical cross ventilation, also facilitates visual lines of sight across the cross-sections of two floors above along with the attendant emotional connectivity for the residents. 

The natural texture and colour of brick, enhanced by the deliberate proportioning of spaces, and accentuated by the interplay of light and shadows (through brick louvers), endows the Lobby area with a sense of warmth and calmness, which is simultaneously welcoming and cathartic for patients. The Nurse's Station and Director's office are located adjacent to the Lobby. The stairs and lift location allows for easy visibility and quick access to the residents’ suites.

The ground floor has a central dining space opening out to an external landscaped area, and serviced by a large commercial kitchen. Additional kitchenettes and tea stations are also located on individual floors. Overall, the architectural detailing was kept restrained and simple to emanate aura of calmness to the space. The Patient care suites are all located on the First & Second floors with each room having space for one patient along with either one or two carers.Suites fronting the site’s main entry have balconies with brickwork louvers allowing cooling breezes whilst maintaining privacy for the residents. 

A common congregation space has been provided on every floor, along with an Activity Room and a Recreation (or TV) room.The built form is contained within a simple platonic geometry–aiming to be classy without the distracting clutter of accouterments. The external façade utilizes a double-slanted louvered brickwork feature wall covering the Recreation Rooms across two floors and cantilevering over the ground floor, whilst poignantly showcasing the architectural possibilities of the humble brick.

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Project location

Address: thiruvananthapuram, kerala, india.

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• Sustainability

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Benziger 临终关怀之家 / Srijit Srinivas - ARCHITECTS

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AIIMS GORAKHPUR HEALTHCARE ARCHITECTURE.THESIS REPORT

2018, JAMIA MILLIA ISLAMIA

A hospital is a health care institution providing patient treatment with specialized medical and nursing staff and medical equipment. A Multi-Speciality hospital typically is the major health care facility in its region, with large numbers of beds for intensive care and additional beds for patients who need long-term care. Specialised hospitals include trauma centres, rehabilitation hospitals, children's hospitals, seniors' (geriatric) hospitals, and hospitals for dealing with specific treatment needs such as Cancer ,Heart treatment and certain disease categories. Specialised hospitals can help reduce health care costs compared to general hospitals

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Rural Habitat, based , on scientific utilization of India's natural resources, has been given highest priority for amelioration of the living conditions of the rural masses. With this aim in view, several efforts were made at rural development to better the socioeconomic lot of villagers from ancient times to British period Rural Habitat is an important national development agenda. In the decades following Independence many economic and infrastructural efforts have been channelled to improve rural areas and bring them into the mainstream of development. Nevertheless, the physical aspect of development has never been given due attention. The main purpose of choosing Basahi Akbalpur is to understand the difference in Architecture of developed Villages and undeveloped villages.This study deals with built and unbuilt areas in the villages and to understand how the Architecture, Planning, Lifestyle has changed in the Past Years. It also deals with the Social, Economic factors that affect the society.Also to study the various aspects that helped in the development of these village The Basahi Akbalpur as the study of tradional Houses or Dwellng units in Basahi Akbalpur .There varities of Traditionla Dwelling Unit (Kutcha Houses) ,in which variety of materials has been used. The key information ofthe research seek is on village and housing types, forms and development characteristics. To this end, the research applies multi-methods which include direct observation, structured and semi-structured interviews, archive and secondary information. The research fmds that the Basahi community are not unlike other villagers in Azamgarh. Ownership to land is priced, family ties highly regarded and that there is strong attachment to the village. With respect to the physical aspects, the growth and development of Basahi village are found to be influenced by factors of land inheritance, topography and increasingly important, access to roads. House type and building material used are also changing as the community in general adopts more modem house design and material. The study also identifies several typical floor plan (design) and average house sizes. RURAL HABITAT ON BASAHI AKBALPUR 2017 MOHD AFZAL DISSERTATION RESEARCH

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New case study: Climate-smart architecture and renewable energy to power a rural hospital in India

Located in the rural area of Masarhi, state of Bihar, India, the  Vistex Hospital  was founded in 2019 with a grant from the  Vistex Foundation  and is operated by the NGO  Doctors for You . The hospital is one of the main health care centers in the region.

Since its inception, the goal of the organization was to build a sustainable, energy-efficient hospital in order to provide consistent and dependable health care and services for their community with a small environmental footprint. 

The area where the hospital is located experiences frequent power cuts. By using on-site solar energy generation, energy-efficient equipment, and climate-smart architecture, the hospital reduced its energy consumption and associated costs by 58%, saving approximately 10,000 US Dollars per year.

The walls of the top floor were constructed using agribio panels made from straw, a residue from the harvest of rice.

“This is a fantastic example of a hospital taking a holistic and comprehensive approach to sustainability. They are mitigating their climate impacts while increasing their resilience to an unreliable power grid with innovative waste, energy, water, and building solutions. In turn, they are improving their ability to serve their community. It’s a win across the board. We are proud to have them as members of the GGHH network.”, says Nick Thorp, Global Green and Healthy Hospitals Network Director. 

“The Vistex Hospital in Masarhi, Bihar is an exemplar of a timely, integrative response to the COVID-19 crisis in India. Whilst responding to the local health care requirements at the height of the pandemic, the health facility was built incorporating the principles of sustainable and environmentally friendly healthcare”, explains Dr. Poornima Prabhakaran, Deputy Director of the Centre for Environmental Health at the Public Health Foundation of India. 

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Evolution of Healthcare Architecture in India

The healthcare model in India is universal, directed by the State, rather than the federal rule. As generally known, the public organization is usually free, except for some symbolic payments. Therefore the Indian State is responsible for raising the living standards of its citizens while assuring the continuous evolution of public health. Indeed, the government spent a total of 36 billion dollars in 2019, which equals around 1.23% of the GDP, for healthcare .

The constant update of the National Health Policy since 1983 focused on the actions of the vital healthcare industry. 

In 2018, the system of health insurance was funded by the government. The idea was launched by Ayushman Bharat, India’s Government . By doing so, 50% of the population was offered free treatment at private institutions. 

Rajiv Gandhi Government General Hospital

Rajiv Gandhi Government General Hospital is one of the oldest significant hospitals owned by the State in India. It is located in Chennai and is currently funded and managed by the government of Tamil Nadu. Today, this healthcare facility supports 2,722 beds and is affiliated with Madras Medical College. 

Rajiv Gandhi Government General Hospital was founded by the British East India Company on November 16th, 1664. Being the first medical institution in India, the hospital was used to treat British East India’s sick soldiers. 

During the first few years, the Government General Hospital was located at Fort St. George. It snowballed to become a formal medical institution thanks to Sir Elihu Yale, who instrumented the hospital’s development by giving it new premises in 1690. Sir Yale is the benefactor of Yale University. 

After the British French war, the Government General Hospital took over 20 years to settle in its current location. By 1772, this healthcare facility was a training house for Europeans, natives, and Eurasians. 

The main building, which is known to have an H-shape, was built in 1842. At that time, the hospital opened its doors to the Indians, and Madras Medical College started functioning as a medical school. The hospital’s expansion was done between the years 1928 and 1938 for the facility to welcome more patients. By the end of the 1990s, the demolition of the old building was ordered. The idea was to replace it with blocks of two towers. 

The city of Chennai is located inside of a critical seismic zone, type III. Therefore, the Rajiv Gandhi Government General Hospital structure was, in fact, thought in a quake-resistant way. Its superstructure consists of pile foundations and a framed structure. The two new towers were built with aluminum, Nova Kote finish, structural glazing, and composite panel cladding. 

In order to allow the flow by the gravity of rainwater, the ground level was raised around 1.40 meters above the ground. Tower I makes an area of 31,559 square meters, whereas tower II 33,304 square meters. These two towers are equipped with three different staircases, eight lifts, and a ramp that facilitates access to all floors. Obviously, a fire-escape staircase is placed separately, as well as a garbage disposal life. The blocks are 8-storeys high. 

The whole Government General Hospital has 52 operation rooms, as well as IC units and post-operative blocks. This hospital became the first to hold an oxygen tank with a capacity of 13,000 liters of oxygen of continence. It was the first to install color-coded areas, according to the Tamil Nadu Accident and Emergency Care Initiative guidelines. 

This facility owns a corporation canteen of 5,000 square feet. It is still under construction but will have the capacity of welcoming 12,000 outpatients and 3,000 inpatients, as well as thousands of people between visitors and hospital staff. This canteen unit will be equipped with an access ramp.

Osmania General Hospital

Osmania General Hospital is one of the oldest healthcare facilities in India too. It was built in 1866, under the name of Afzal Gunj Hospital by Salar Jung I. The last Nizam of Hyderabad, Mir Osman Ali Khan, ordered the completion of the actual hospital building in 1919. Nowadays, the Osmania General Hospital is home to more than a thousand beds. 

OGH was designed by the British architect Vincent Jerome Esch and Nawab Khan Bahadur Mirza Akbar Baig. It has an architectural style called the Indo-Saracenic style. The Indo-Saracenic style, also known as the Neo-Mughal, or Hindu Style, was a revivalist architectural style that aimed at bringing back elements from the native Indo-Islamic Architecture. It was used by British architects who were in India during the 19th century.

Tata Medical Center

From 1900 to 2016, India has seen a doubling in cases of cancer and cancer-related deaths. The main reason? The shortage of accessibility to treatment. 

In that framework, the Tata Medical Center was conceived: the shed of light that would increase cancer survival rates. In 2019, these numbers were around 80% of survival in Kolkata, where the hospital is located. This healthcare facility was designed by CannonDesign and partnered with international manufacturers such as AutoDesk, Saint-Gobain, Hunter Douglas, and others. 

2011 was the year when the Tata Medical Center opened its phase I units. During that phase, a considerable demand had to be cut out due to the lack of available beds. Doctor Mammen Chandy, the Tata facility director, claims that around 30% of patients were rejected. However, when phase II of construction was completed in 2019, 240 beds were added to the initial buildings. Additionally, an academic medical research center was injected so that students and visiting faculty members could enhance their knowledge. 

The main aim of this healthcare facility is to improve the experience. One shouldn’t forget that these patients are facing life-saving treatments and should be present in the most pleasant environment possible. The gradation between public and private space is made subtle thanks to courtyards. In that sense, the facility becomes a friendlier, campus-like hospital. 

Bouncing back to the idea of private treatment paid by government insurance that we discussed earlier, the Tata Medical Center offers more than 50% of its inpatient’s free treatment. This forms a significant critical evolution in cancer detection and early treatment.

A Considerable Change

As times pass by, technologies evolve, and knowledge grows, the Indian Healthcare system never accepts going back. The continuous increase of will to change and upgrade healthcare facilities is alimented by the government’s desire to make medicine and treatment more accessible, reachable, affordable, and amazingly humane design standards. 

As we saw through those three examples, having each one its own divergent perceptions, all of them agree that hospitals should promote comfort and stress-free environments. Adding on to that, the demand for hospitalization is growing bigger and bigger. This leaves this kind of facility under a challenge, which they are successfully winning.

Dima Fadel is a passionate and curious architect, constantly seeking new knowledge. She graduated with a Bachelor Degree in Architectural Studies from the Académie Libanaise des Beaux-Arts in Beirut last summer, and is currently pursuing her MSc in Integrated Architectural Design at La Salle, in the urban laboratory of Architecture: Barcelona.

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• Open access
• Published: 03 April 2024

Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study

• Mahendra Atlani 1   na1 ,
• Ashok Kumar 2   na1 ,
• Rajesh Ahirwar 3 ,
• M. N. Meenu 1 ,
• Sudhir K. Goel 2 ,
• Ravita Kumari 2 ,
• Athira Anirudhan 1 ,
• Saikrishna Vallamshetla 4 &
• G. Sai Tharun Reddy 4  

BMC Nephrology volume  25 , Article number:  120 ( 2024 ) Cite this article

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Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India.

The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases ( n  = 60) were compared with CKD ( n  = 62) and healthy subjects ( n  = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test.

CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3–132.7) µg/L compared to CKD 4.5 (0.0–58.8) µg/L and healthy subjects 39.01 (4.8–67.4) µg/L ( p  < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003–1.024) P  < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu ( p  > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects ( P  = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029–9.818) p  < .05).

The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

Peer Review reports

Chronic kidney disease of unknown cause (CKDu) has been reported in various parts of the world (i.e., Nicaragua, El Salvador, Sri Lanka), including India, as an endemic disease. The disease is a diagnosis of exclusion, made when a patient fulfils the Kidney Disease Improving Global Outcomes (KDIGO) CKD criteria but without the evidence of a recognized cause such as diabetes, hypertension, or glomerulonephritis [ 1 ]. No uniform and definite cause has yet been identified, though various environmental factors have been associated with and suggested to play a role in the pathogenesis. For example, heat stress, strenuous exercise, agrochemicals, and heavy metals have been held responsible for Mesoamerican nephropathy [ 2 ]. Mixed evidence has been reported for association with agrochemicals, heavy metals, and genetic variability for CKDu in Sri Lanka [ 3 , 4 , 5 ]. In India, one small study reported an association of heavy metals with CKD [ 6 ]. A study done on groundwater samples from the Uddanam region of Andhra Pradesh (India), which has a high prevalence of CKDu reported water as acidic (pH < 6.5) and to contain higher silica and lead in wet and dry seasons, respectively. Phthalates were also detected in the groundwater [ 7 ]. Previous studies have attempted to find a correlation between heavy metals and CKDu by comparing cases and endemic and nonendemic controls [ 4 ]. No study has yet tried to find the association of heavy metals comparing CKDu with CKD. Furthermore, previous studies have used urinary metal levels as a biomarker of metal exposure. There is an inherent issue of reverse causality i.e., reduced excretion of metals in urine with a reduction in glomerular filtration rate (GFR) [ 8 ]. Measurement of metals in blood has also been reported to be a promising biomarker of metal exposure [ 9 , 10 ]. Some studies have employed urine to blood ratio for deciding whether urine or blood levels should be used for a particular metal. For metals with urine/blood ratio more than one blood metal levels, whereas for metals with urine/blood ratio less than one, urine metal levels were used in estimation analysis [ 11 ]. The purpose of this study was to test hypothesis whether heavy metals i.e. Arsenic (As), Cadmium (Cd), Lead (Pb) and Chromium (Cr) are associated with CKDu, in central India using blood and urine levels as biomarker of metal exposure.

Materials and methods

Study setting and population.

Study was conducted in a tertiary care hospital setting in the Department of Nephrology in India in a case-control design between December 2019 to June 2022. Participants were enrolled between December 2019 -December 2021. The data collection was done simultaneously. The sample analysis was carried out between January to June-2022. The study was performed according to the guidelines of the Declaration of Helsinki. The study objective was to compare CKDu cases with CKD and healthy controls with regard to biomarkers of exposure of heavy metals [blood and urine levels of cadmium (Cd), lead (Pb), arsenic (As) and chromium (Cr)]. The study included adults aged 18–70 years with CKDu and two groups of the control population, one with CKD and another group of healthy controls without evidence of CKD.

The CKDu and CKD cases were inducted among the patients visiting the nephrology outpatient department and based on pre-defined criteria. At the same time, healthy controls were inducted among the healthy relatives accompanying the patients visiting other departments of the institute for treatment. Written informed consent was obtained from all the participants.

The case definition of CKDu was based on criteria proposed by the Indian Society of Nephrology for the diagnosis of CKDu [ 12 ]. The inclusion criteria included- eGFR < 60 mL/min/1.73m2 (CKD-EPI) [ 13 ] and albumin-to-creatinine ratio (ACR) > 30 mg/g for more than 3 months with:

Urine protein creatinine ratio(PCR) less than 2g/g.

No history of glomerulonephritis, pyelonephritis, renal calculi, polycystic kidneys or obstruction on renal ultrasound.

Not on treatment for diabetes and HbA1c less than 6.5%.

Blood pressure less than 140/90 if CKD stage 1 and 2; and less than 160/100 if CKD stage 3,4, and 5 and on a single drug for blood pressure control.

Case definition of CKD was based on: eGFR < 60 mL/min/1.73m2 (CKD-EPI) and albumin-to-creatinine ratio > 30 mg/g for more than 3 months. Patients were included in the CKD group only if PCR > 2g/g. Hypertension with BP > 140/90 in stages 1–2 and > 160/100 in stages 3–5 or on two or more drugs for BP control.

CKD staging was based on the KDIGO-2008 classification [ 1 ]. The same stages were applied to categorize the renal functions of subjects with CKDu.

Inclusion criteria for healthy controls included: Absence of CKD as evidenced by eGFR more than 90 ml/min/1.73m2, ACR < 30mg/g and lack of anatomical renal disease, obstruction or stone on renal ultrasound, no history of diabetes, HbA1C less than 6.5 and BP less than 140/90.

Biases were kept a minimum by adhering to the case definition described above, and study exposures are mainly objectively assessed with very less dependency on recall i.e. for pesticide or painkiller use. The urine metal levels were adjusted for urine dilution by estimating metals per gram of creatinine in urine.

Sample size

Assuming a difference of moderate effect size (0.25), between three groups (CKDu cases, CKD Controls, Normal Controls) with a confidence level of 95% and power of 80%, the calculated sample size was 159. The final sample size estimated, including a 10% non-response rate, was 180 (60 per group).

Specimen collection and analysis

For the analysis of heavy metals, venous blood (2 ml) was collected in trace element free Trace Element K2-EDTA Vacutainer (Cat# BD 368381). Whole blood was stored at -40 °C until analysis. Ten millilitres (10 ml) of first-morning urine was collected in 50 ml polypropylene tubes. Urine was stored at -40 °C in aliquots until analysis. Serum and urine creatinine was measured using a modified kinetic Jaffe’s method using a Random Access Fully Automated Chemistry Analyzer (Beckman Coulter). Urinary protein and urine albumin were estimated using a colorimetric and immune-turbidimetric methods, respectively, using a Random Access Fully Automated Chemistry Analyzer (Beckman Coulter). HbA1c was analyzed by ion-exchange high pressure liquid chromatography method using a D10 Haemoglobin testing system (BioRad Laboratories). eGFR was calculated from serum creatinine and CKD -EPI equation (Ref). A kidney ultrasound was performed in standard B Mode grey scale in 3.5–5 MHz, the longitudinal length was measured along with the width and thickness of the kidney, renal stones, and any other anatomical abnormality.

Estimation of heavy metals in blood and urine

Levels of Cd, Pb, Cr and As were measured in whole blood and urine. Urinary spot sample results of metal analysis were adjusted for dilution by urine creatinine. Metal analysis was carried out at NIREH, Bhopal (India).

Levels of various heavy metals, viz. Cd, Pb, Cr, As in the collected blood and urine samples were analyzed through inductively coupled plasma optical emission spectroscopy (iCAP® 7400 Duo ICP-OES, ThermoFisher Scientific® Pvt. Ltd). Blood and urine samples were acid-digested in a microwave oven prior to metal detection on ICP-OES. For blood digestion, 1 mL of whole blood sample was mixed with 6 ml of a freshly prepared mixture of concentrated trace metal grade nitric acid (HNO3) and hydrogen peroxide (H2O2) in a ratio 2:1 (v/v) in high-purity polytetrafluoroethylene (PTFE-TFM) vessels. For urine digestion, 5 mL of urine sample was mixed with 6 ml of a freshly prepared mixture of HNO3 and H2O2 in a ratio of 2:1. After gentle mixing of these reactants with blood, the PTFE-TFM vessels were arranged in the rotor (24HVT80, Anton PAAR) and digestion was carried out in the Anton Paar, multi microwave PRO Reaction System at 200 C for 15 min. Digested samples were cooled to 40°C and diluted to 30 ml with distilled water. Blank was prepared for each cycle of digestion using distilled water, nitric acid, and hydrogen peroxide mixture. All the chemicals were trace-element free.

Before the analysis of metal ions in processed blood and urine samples, calibration standards for each element were prepared from multi-element stock solutions (1000 mg L − 1) in triple distilled water. Detection of Cd, Pb, and Cr was performed using a standard sample introduction setup, whereas for As, the hydride generation sample introduction system was utilized. Online hydride generation for As was achieved with an Enhanced Vapor System sample introduction kit using 0.5% m/v sodium tetrahydroborate (NaBH4) stabilized in 0.5% m/v NaOH and 50% v/v HCl solution. Emission data acquisition was performed using the Qtegra ISDS Software at interference-free wavelengths.

Statistical analysis

Statistical analyses were performed with R version 4.2 (R Foundation for Statistical Computing, Vienna, Austria) and IBM SPSS 26 version. The distribution of data in groups was evaluated with Shapiro-Wilk, kurtosis, skewness, and histograms. Skewed data for three groups was compared with the Kruskal-Wallis test. Subgroup analysis in three groups was performed with pairwise comparisons by Dunn test. Parameters with homogeneous distribution were compared with the chi-square test. Data are presented as %, for categorical variables or as median (Q1-Q3) for continuous variables.

Detection rates for blood and urinary metal levels were calculated. For urine metal levels, all statistical analyses were performed with creatinine-adjusted metal concentrations.

Urine to blood ratio was calculated for all metal levels. Spearman correlation coefficient was used to find the association between blood and urine metal levels of individual metals as well as for the association between different metals both in blood and urine. Correlation of blood and urine As with GFR was also performed.

We performed multinominal regression analysis for significantly different metal level in CKDu cases with respect to CKD and healthy controls. We included age and gender (confounding factors) in the model to see the y independence of association and effect estimate of the factor associated with CKDu. Regression model matrices and goodness-of-fit were also determined by the pseudo R 2 coefficient and Hosmer-Lemeshow goodness-of-fit test.

For all analyses, we have considered a p -value less than 0.05 as statistically significant.

A total of 568 patients who visited Nephrology OPD during the study period were screened for inclusion in the study. Out of these, 66 CKDu and 70 CKD cases were found eligible to enroll in the study. Eight patients withdrew consent in the CKD group, whereas four patients in the CKDu group had uncontrolled blood pressure with a single drug, and two withdrew consent. Finally, 60 CKDu and 62 CKD cases were included in the study for outcome analysis. We have approached 120 relatives of patients attending other OPDs and screened them for eligibility criteria of the healthy control group. Out of these, 60 were eligible, and 54 provided consent for participation in the study.

Demography and lab parameters

The CKD and CKDu subjects were similar in demographics for age and sex. However, healthy subjects were younger (Table  1 ). There was no significant difference between CKDu and CKD with reference to stage V (32 vs. 44, P-0.107).There were 05 diabetic kidney disease 04 CKD due to secondary glomerular disease patients (3-lupus nephritis, 1-FSGS), 12 hypertension-associated renal disease, 01 ADPKD, 36 Chronic glomerulonephritis patients, and 04 Chronic pyelonephritis patients in the CKD group. Use of smoking, Alcohol, and painkillers was similar across the three groups (Table  1 ). A significant difference was found between the three study groups with respect to the source of drinking water (ground or surface water). A significantly higher number of CKDu subjects used surface water as a source of drinking water (Table  1 and Table-S 1 and Fig-S 1 ) and a higher number of CKDu subjects reported pesticide usage. As shown in Table  1 , blood pressures were significantly higher in CKD subjects compared to CKDu and healthy subjects and reflect the inclusion criteria with appropriate patient inclusion in three groups. Both ACR and PCR were also significantly different between CKD and CKDu. The eGFR was calculated based on the CKD-EPI formula and was not significantly different between the CKD and CKDu subjects, however, CKD subjects had lower median eGFR compared to CKDu subjects. The healthy subjects had significantly higher eGFR compared to both groups. HbA1c, were similar across the three groups (Table  1 ).

Analytical results

The urinary and blood levels of As, Cd, Pb, and Cr (Table  2 ) were measured in ppb (micrograms per litre), and median with interquartile ranges were reported. Urinary metal levels were also measured in ppb (micrograms per liter) and then adjusted for urinary dilution by urine creatinine value and were finally expressed as micrograms/grams of urine creatinine (Table  2 ).

Detection limits

The lowest detectable concentrations of various heavy metals analyzed on ICP OES with a signal-to-noise ratio of 1 were as follows: As (193.759 nm) - 0.191 ppb; Cd (214.438 nm) - 0 ppb; Pb (220.353 nm) - 0.822 ppb; Cr (283.563 nm) - 3.156 ppb (Table  2 , Figs-S 2 -S 5 ).

Detection percentage

The number of subjects with blood and urine metal levels above the respective detection limits in each study group is reported in Table  2 .

Urine to blood ratio

A urine/blood ratio for each metal in all study groups was calculated for patients with metal levels above the detection limit. The distribution of urine/blood ratios for all metals is presented in Table  2 . Ratios were different between healthy and subjects with deranged kidney functions i.e. low GFR (CKD and CKDu). Median urine/blood Ratio for As was > 1 in healthy subjects and < 1 in CKD and CKDu, reflecting higher urinary levels compared to blood in healthy and reverse in CKD and CKDu subjects. For Pb, it was < 1 in healthy subjects and > 1 in subjects with CKD and CKDu, reflecting higher blood levels compared to urine in healthy and reverse in CKD and CKDu subjects. For Cd and Cr the ratio were < 1 across all three groups suggesting higher urine levels compared to blood levels.

Correlation

A spearman correlation (ρ) was also performed to see the association between each urine and blood metal and among the metals with each other as well. In CKDu, UAs were negatively associated with BAs (ρ-0.260, p -0.11) and in CKD positively (0.138, p -0.37). There was a positive association between urine and blood levels of As,Pb, and Cr and negative association of urine and blood Cd in CKD. In CKDu, a positive association was found in blood and urine Cd,Pb and Cr. In addition, there was a strong correlation of blood Cd, Pb, and Cr ( p  < 0.01) [ρ = 0.68 (BCd and BPb), 0.88 (BCd and BCr), 0.71 (BPb and BCr) in CKDu and [ρ = 0.55 (BCd and BPb), 0.82 (BCd and BCr), 0.65 (BPb and BCr) in CKD. The Urine Cd, Pb, and Cr also had strong correlations [ρ = 0.33 (UCd and UPb), and 0.48(UPb and UCr)] in CKD and [ρ = 0.19(UCd and UPb), 0.67 (UCd and UCr), and 0.69 (UPb and UCr)] in CKDu < 0.05 (Table-S 2 -S 4 and Fig-S 6 ). Association of Blood and urine As with GFR was also evaluated, and BAs were found to be negatively associated with GFR (ρ = -0.097, p  = 0.56), whereas UAs were positively associated (ρ = 0.14, p  = 0.25) with GFR (Table-S 5 ). Metal levels: Blood As: was significantly higher in CKDu ( n  = 37) subjects compared to CKD ( n  = 41) and healthy ( n  = 53) subjects (Table  2 ). On the other hand, the urinary As (UAs) was significantly low in CKD ( n  = 50) and CKDu ( n  = 48) subjects compared to healthy subjects ( n  = 38) and was non significantly higher in CKD subjects compared to CKDu subjects (Fig.  1 , Table  2 ).The blood and urine As values were below detection limits in 21.6%, 35.7%, and 18.8% and in 6%, 16.6%, and 0% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine arsenic according to diagnosis categories. Median; microgram/Lt (blood); microgram/gm(urine); UAs- Urine arsenic;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Blood Cd also was significantly higher in CKD and CKDu subjects compared to healthy subjects. Urinary Cd (UCd) levels were significantly higher in CKD and CKDu subjects compared to healthy subjects,. There was a weak association of ( p  = 0.06) UCd with CKD subjects compared to CKDu subjects.UCd was higher in CKD subjects compared to CKDu (Fig.  2 , Table  2 ). The blood and urine Cd values were below detection limits in 8.3%, 8.1%, and 0% and 37.2%, 19.3%, and 75.9% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine cadmium according to diagnosis categories. Median, microgram/Lt (blood); micrograms/gm (urine); UCd- Urine cadmium;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Pb levels in the blood of CKD and CKDu as well as in urine of CKD and CKDu subjects were significantly higher compared to healthy subjects. The Pb levels were higher in CKD subjects compared to CKDu subjects, but it was not statistically significant (Fig.  3 , Table  2 ). The blood and urine Pb values were below detection limits in 15%, 20%, and 25.9% and 23.3%, 19.4% and 70.4% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine lead according to diagnosis categories. microgram/Lt (blood); microgram/gm(urine); UPb- Urine lead;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

As shown in Table  2 and Fig.  4 , urinary and blood Cr was significantly higher in CKD, and CKDu patients than healthy subjects. The blood and urine Cr values were below detection limits in 13%, 0%, and 0% and 13.3%, 14.5% and 85.2% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine chromium according to diagnosis categories. Median; microgram/Lt(blood); microgram/gm(urine); UCr-urine chromium, CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Multinominal regression

Though age, gender, were not significantly different between CKDu and CKD, on univariate analysis, we included these In the multinominal regression analysis between CKDu and CKD in reference to healthy subjects in addition to factors found significantly different ( p  < 0.01 on univariate analysis) i.e. blood As and source of drinking water.After the final model, gender had no association with CKDu. Blood As, surface water as drinking water source and age were independently associated with CKDu. Age was associated independently with CKD also (Table  3 ).

To the best of our knowledge, this is the first study wherein an attempt has been made to analyze the association of heavy metals with CKDu in central India, using blood and urine levels as biomarkers of metal exposure. In addition, CKD and healthy subjects have been used as control groups.

The current study showed that blood and urine creatinine-adjusted urinary levels of heavy metals Cd, Pb and Cr were significantly higher in patients with CKD and CKDu as compared to healthy subjects. The urinary levels of the above metals were undetectable in healthy subjects. The study also showed a weak association of ( p  = < 0.06) higher urinary Cd in CKD subjects compared to CKDu subjects of this Indian cohort.

The study also showed that Blood As was significantly higher in CKDu subjects compared to CKD and healthy subjects. On multinominalregression, blood As was independently ( p  < 0.05) associated with CKDu after age adjustment.

In our study, median GFR was rather high in CKDu subjects [14.5 (7.0, 34.2)] compared to GFR in CKD subjects [9.0 (6.0, 17.0)ml/min/1.73m 2 )] and it was non significantly different between the two groups. On correlation analysis, there was a negative correlation between Blood As and GFR and a positive correlation of urine As with GFR. Based on this, the higher blood As in CKDu with higher GFR appears to be truly elevated.

Previously a study from Sri Lanka has also reported an association of CKDu with chronic As toxicity. In that study, 48% of CKDu patients and 17.4% of the control subjects fulfilled the criteria to be diagnosed with chronic arsenical toxicity(CAT), indicating the potential link between CAT and CKDu and suggesting agrochemicals could be the possible source [ 14 ]. Later, it was reported that glyphosate was the most widely used pesticide in Sri Lanka, which contains an average of 1.9 mg/kg arsenic. Findings suggest that agrochemicals, especially phosphate fertilizers, are a major source of inorganic arsenic in CKDu endemic areas [ 15 ]. However, another study from Sri Lanka did not find any difference in UAs levels in patients of CKDu in endemic areas and controls from endemic and nonendemic areas [ 4 ].

Some other studies have reported associations of As with CKD. A study from Taiwan found total UAs to be associated with a four-fold risk of CKD [ 6 ]. Another study reported an association of MMA V (mono methyl arsenate pentavalent) and DMA V (dimethyl arsenate pentavalent) in urine with prevalence of CKD [ 16 ]. However, in both studies, the type of CKD was not reported.

The higher blood As in CKDu compared to CKD may be associated with exposures in our study; a significantly higher number of subjects in CKDu group reported use of pesticides, surface water as a source of drinking water in CKDu subjects.On regression analysis also, surface water was independently associated with CKDu.

A study from north India reported increased levels of OCPs, namely α-HCH, aldrin, and β-endosulfan, in CKDu patients as compared to healthy control and CKD patients of known etiology [ 17 ] and it is also known that arsenic is an important component of pesticides [ 18 ]. The contamination of surface water with various pollutants i.e. pesticides, is common [ 19 ]. Arsenic is a known nephrotoxin, and one of the case reports where kidney histopathology was evaluated reported As causes tubulointerstitial disease (TID) [ 20 ]. The difference in methylation processes of As has also been found responsible for various diseases associated with As i.e. for example, high proportions of urinary MMAs (%U-MMAs) have been associated with a higher risk of cancers and skin lesions [ 21 ]. In contrast, high %U-DMAs has been associated with diabetes risk [ 22 ]. We have measured only iAs in our study. Whether methylation resulting in various metabolite species has different associations with CKDu or CKD should be explored further. We recently found a significant association of single nucleotide polymorphism in a gene coding for sodium-dependent dicarboxylate transporter (SLC13A3) with the susceptibility to CKDu [ 23 ].

In the current study, the UAs results suggest that As levels of 97 µg/gm of creatinine in healthy subjects were not associated with decreased GFR or proteinuria. Similar results were reported by a study from China where researchers found a lower confidence limit on the benchmark dose (LBMD) of 102 and 0.88 µg/gm creatinine for As and Cd, respectively, in order to prevent renal damage in the general population co-exposed to arsenic and cadmium [ 24 ]. The UAs in healthy subjects in our study were nearly similar to the LBMD reference and, not surprisingly, not to be associated with CKD or proteinuria.

Some studies have reported lead to be associated with CKDu. An Indian study reported high levels of lead and silicon concentrations in Indian groundwater in the endemic Uddanam area [ 7 ]. Jaysuman et al. also reported higher levels of Pb (26.5 µg/gm) in the urine of patients with Sri Lankan agricultural nephropathy compared to endemic and nonendemic control [ 25 ].

In the current study, although the median level of blood Pb was almost double in CKD patients compared to CKDu, the result was not statistically significant.

Our study showed that Cd was significantly associated with renal disease. Blood Cd and urine Cd (UCd) levels were significantly higher in patients with renal disease (CKD and CKDu) as compared to healthy subjects. The findings of UCd also showed a weak association (p-0.06) of Cd with CKD compared to CKDu among patients with renal diseases. There are some concerns that UCd may not be truly reflective of metal burden in patients with advanced CKD [ 26 ], because initially, in the course of Cd toxicity with early tubular damage, the normal reabsorption of cadmium-metallothionein decreases, and the UCd concentration increases. However, in the long run, cadmium-induced kidney damage gives rise to low Cd concentrations in both the kidney and urine, while the tubular damage remains [ 27 ]. The U/B ratio of < 1 for Cd in our study supports the above findings.

The mean eGFR in our CKD cohort was lower compared to CKDu; despite this, higher UCd values in patients with CKD compared to CKDu in our study indicate a potential association of Cd with CKD.

Studies have reported variable association of Cd with CKDu when compared to healthy subjects. Nanayakkara et al. [ 28 ] did not find an association of UCd with CKDu in stages 1–4 compared to healthy controls. Whereas another Sri Lankan [ 4 ] study found significantly high UCd in patients with CKDu against the endemic and nonendemic controls. We also observed significantly higher UCd in CKDu vs. healthy controls.

In the current study, urinary Cr (UCr) was not detected in healthy subjects, whereas it was significantly higher in patients with CKD and CKDu as compared to healthy subjects. UCr levels were higher in CKD compared to CKDu. Epidemiologically, Cr exposure has been reported to be associated with kidney damage in occupational populations [ 26 ]. Recently, a study from Taiwan reported that a significant and independent association between Cr exposure and decreased renal function in the general population, and co-exposure to Cr with Pb and Cd is potentially associated with an additional decline in the GFR in Taiwanese adults [ 27 ]. A study from Bangladesh reported outcomes similar to our study; however, the study included only CKD ( n  = 30) patients and compared them with healthy subjects ( n  = 20). In that study, compared to the controls, CKD patients exhibited significantly higher levels of Pb, Cd, and Cr levels in their urine samples. This signifies a potential association between heavy metal co-exposure and CKD [ 29 ]. In the current study a significant correlation between blood Cd, Pb, and Cr and urine Cd, Pb, and Cr were found in CKDu and CKD subjects compared to healthy subjects. The levels of UCd, UPb, and UCr in CKD and CKDu patients were significantly higher compared to healthy controls; The possibility of the combined effect of Cd, Pb, and Cr in the causation of renal diseases could be evaluated further in future studies. As CKDu is an endemic disease, the results of our study suggest an association of arsenic with CKDu in the Indian population, and so the generalizability of the result should be used with caution.

Strengths and limitations

This is the first study which has included two controls (CKD and healthy) and compared metal levels in patients with CKDu. In addition, the comparison of metals in both blood and urine is another advantage, as falling GFR levels and urine levels of several metals do not reflect true metal burden in patients. Inclusion of CKDu patients, as per the suggested definition by the Indian society of Nephrology, is another strength of our study.

The small sample size of our study may be a limitation of our study though it was calculated scientifically. The study involved Indian patients and controls only so the generalization of the results should be with caution. Healthy controls were of younger age is also a limitation of the study.

Also the study included patients from central India, comparatively a larger area and does not points out endemicity.

The study finds an association of environmental toxins with CKDu and CKD. The age and sex-adjusted As were observed to have an independent association with CKDu. A weak association of Cd with CKD was also observed in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were observed to have a significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu patients may have higher exposure to As via pesticides, surface water usage, or both.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Chronic Kidney Disease of unknown cause

Chronic Kidney Disease

Kidney Disease Improving Global Outcomes

Glomerular filteration rate

Institutional Human Ethics committee

Concentrated trace metal grade nitric acid

Hydrogen peroxide

High-purity polytetrafluoroethylene

Inorganic As

Tubulo-interstitial disease

Pentavalent monomethylarsonic acid

Pentavalent dimethylarsinic acid

Methylarsenous acid

Sodium-dependent dicarboxylate transporter

Limit on the benchmark dose

Arsenobetaine

Urinary MMAs

Urinary DMAs

Blood lead levels

End-stage kidney disease

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Acknowledgements

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The Study was funded by Indian council of Medical Research (ICMR),New Delhi, India. Sanction no.:5/4/7-14/2019-NCD-II.

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Mahendra Atlani and Ashok Kumar contributed equally to this work.

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Department of Nephrology, All India Institute of Medical Sciences (AIIMS), Room No-3022, Academic Block, 3rd Floor, Saket Nagar, Bhopal, Madhya Pradesh, 462020, India

Mahendra Atlani, M. N. Meenu & Athira Anirudhan

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Saket Nagar, Bhopal, Madhya Pradesh, 462020, India

Ashok Kumar, Sudhir K. Goel & Ravita Kumari

Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, Madhya Pradesh, India

Rajesh Ahirwar

All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India

Saikrishna Vallamshetla & G. Sai Tharun Reddy

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MA and AK were equally involved in conceptualising the study, winning the grant, analyzing the results, monitoring the progress of study. MA prepared the manuscript. AK and SKG did the editing. RA supervised analysis of metal levels, sample collection done by MMN, RK. Metal analysis done by AA. Data entry and file preparation for results done by MMN, AA, SKV and STR.

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Atlani, M., Kumar, A., Ahirwar, R. et al. Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study. BMC Nephrol 25 , 120 (2024). https://doi.org/10.1186/s12882-024-03564-4

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Received : 28 April 2023

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DOI : https://doi.org/10.1186/s12882-024-03564-4

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