Short summary: Uddanam nephropathy (often called Uddanam CKD or CKDu — Chronic Kidney Disease of unknown etiology) is an unusually high burden of chronic kidney disease clustered in the Uddanam area of Srikakulam district, Andhra Pradesh, India. It affects predominantly agricultural communities, is frequently not linked to the usual causes (diabetes or long-standing hypertension), and appears to be a multifactorial condition with environmental, occupational, social and possibly genetic contributors. This article reviews the epidemiology, proposed causes, key research findings, clinical features, public-health implications and current directions for prevention and care — with clear, practical messages for clinicians, researchers and policy makers.
Introduction — why Uddanam matters
In a small coastal region of north-coastal Andhra Pradesh called Uddanam, clinicians and public-health workers first noticed an alarmingly high number of people with chronic kidney disease (CKD) starting in the 1990s. Over the next decades that observation matured into a public-health crisis: community surveys and hospital records repeatedly documented much higher CKD prevalence and mortality in Uddanam than in neighboring areas, with many patients lacking the usual causes of CKD such as diabetes or long-standing hypertension. Because the cause in many cases remained unclear, investigators adopted the term CKDu (chronic kidney disease of unknown etiology) — the same label used for similar hotspots in Sri Lanka and Central America. Understanding Uddanam is important not only for local health but also as a window into environmental and occupational kidney disease worldwide.
How big is the problem? — Epidemiology and community studies
Multiple well-conducted surveys and community studies have measured CKD prevalence in Uddanam and adjacent districts:
- Early population and hospital-based reports documented much higher CKD prevalence than national averages. A landmark study by Tatapudi and colleagues confirmed a high prevalence of CKD and CKDu in Uddanam compared with other Indian regions. PMC
- A systematic, community-level study by Gummidi et al. (and collaborators) used door-to-door screening and clinical evaluation to confirm a strikingly high burden of CKD in adult populations in Uddanam, with a large proportion of cases lacking traditional risk factors. PMC
- More recent analyses and reviews continue to show CKD as a leading cause of death in the region and call attention to the persistent health system and socioeconomic consequences. KReports
In short: Uddanam’s CKD burden is large, persistent, and a major cause of premature mortality and economic stress in affected communities.
Who is affected — demographics and risk groups
Several consistent epidemiologic patterns emerge from studies:
- Rural agricultural workers — particularly rice farmers and manual labourers — show higher prevalence than non-farmers. Farming appears repeatedly as a common occupation among cases.
- Men are often over-represented in many CKDu cohorts worldwide (though Uddanam data show both genders affected), and the disease is commonly detected in working-age adults rather than the elderly.
- Conventional risk factors (long-standing diabetes, severe hypertension, autoimmune kidney disease) do not account for a large proportion of cases — hence the term CKDu. Many patients have minimal proteinuria and present with progressive interstitial kidney injury on biopsy.
These patterns point toward occupational and environmental contributions layered on background individual susceptibility.
What does the kidney look like? — pathology and clinical features
Clinically and histologically, Uddanam CKDu commonly shows:
- Insidious onset — patients may have subtle symptoms for years (fatigue, reduced urine output, nocturia) and are diagnosed at advanced stages.
- Minimal proteinuria — unlike diabetic nephropathy, heavy albuminuria is often absent.
- Tubulo-interstitial pattern — kidney biopsies (where available) often reveal chronic interstitial nephritis and tubular atrophy rather than classic glomerular disease, consistent with other CKDu hotspots.
This histologic pattern supports theories involving repeated subclinical tubular injury (for example from heat, dehydration, toxins or repeated episodes of acute kidney injury) rather than immune-mediated glomerular disease.
Proposed causes: why is the origin still debated?
Despite intensive research for more than a decade, no single cause has been proven. Instead, the evidence points to multifactorial causation. Proposed contributors include:
1. Occupational heat stress and recurrent dehydration
A leading hypothesis — extrapolated from the Mesoamerican nephropathy (Central American) literature — is that repeated heat stress and dehydration in field workers can trigger subclinical acute kidney injury (AKI) episodes that accumulate and progress to chronic interstitial fibrosis. Several physiologic and epidemiologic lines of work support heat-related kidney injury as a plausible and preventable pathway. Studies modeling climate-related risk and occupational exposure show strong links between strenuous outdoor work in hot climates and CKD.
2. Agrochemical and pesticide exposure
Many investigators have explored pesticides, herbicides and agrochemical exposure as possible causal or co-causal factors. The evidence is mixed: some ecological and case-control studies report associations, but direct causal proof is lacking and confounded by co-exposures (heat, water contaminants, socioeconomic factors). Systematic reviews suggest occupational agriculture and certain chemical exposures increase CKDu risk in some settings, but the picture is complex and region-specific.
3. Groundwater and trace elements
Investigators have tested groundwater quality (hardness, heavy metals, fluoride, silica, pesticides) in Uddanam for nephrotoxic contaminants. Some studies identify elevated levels of certain elements or combinations, but findings are inconsistent across surveys and often do not fully explain case distribution. Groundwater may be one contributor but seems unlikely to be the sole cause.
4. Infectious and inflammatory triggers
Hypotheses include chronic unnoticed infections or inflammatory exposures, but compelling evidence is lacking. Some patients have histories of recurrent febrile illnesses or gastrointestinal symptoms, but causal pathways remain speculative.
5. Genetic susceptibility and epigenetics
Genetic predisposition may explain why only some exposed workers develop CKD. ICMR-sponsored genetic studies and other teams have searched for susceptibility loci, but no single gene has been identified; the most plausible model is gene–environment interaction rather than monogenic disease.
6. Lifestyle and socioeconomic context
Tobacco chewing, alcohol use, poor nutrition, low healthcare access, and late presentation are important modifiers that amplify disease impact and progression. Recent local studies also highlight social determinants (education, caste, poverty) as relevant risk enhancers.
Takeaway: The likely reality is a syndrome where occupational heat stress/dehydration, chemical/environmental exposures, social determinants, and host susceptibility combine in different proportions to produce the observed CKD in Uddanam.
Strongest evidence to date — what studies tell us
Several high-impact reviews and field studies have shaped current thinking:
- Comparative hotspot reviews (NEJM, Lancet reviews) place Uddanam alongside Sri Lankan and Mesoamerican CKDu and emphasize shared features — rural agricultural workers, tubulo-interstitial pathology, and absent classic risk factors — suggesting convergent causal mechanisms like repeated AKI from heat and toxins.
- Community prevalence surveys (Tatapudi, Gummidi et al.) provided rigorous population estimates and identified occupation and certain lifestyle correlates. These studies strengthened the case that Uddanam is an endemic hotspot rather than an artefact of referral bias.
- Groundwater assessments measured elements and showed some worrying patterns in water chemistry, but the heterogeneity of findings across villages implies that water alone may not explain disease clusters.
A recent meta-analysis and global reports emphasize that CKDu is a multifactorial public health problem, requiring cross-disciplinary interventions — occupational, environmental, clinical and social.
Clinical approach — how to screen, diagnose and manage patients in Uddanam
Screening and early detection
- Community screening (eGFR, urine dipstick/protein) is vital because many patients are asymptomatic until advanced stages. Mobile screening camps and point-of-care creatinine testing have been used in local programmes.
Diagnostic workup
- Full history with emphasis on occupation, heat exposure, agrochemical use and water source; physical exam; serum creatinine/eGFR; urinalysis; urine protein quantification; imaging (renal ultrasound).
- Renal biopsy in select cases (when clinically indicated) can demonstrate chronic tubulo-interstitial nephritis, supporting CKDu diagnosis.
Management principles
- Prevent further kidney injury: hydration, salt/electrolyte correction, treat intercurrent infections promptly, avoid nephrotoxins (NSAIDs, unnecessary herbal remedies).
- Control comorbidities: detect and treat hypertension; manage anemia and malnutrition.
- Renal replacement when required: dialysis services and transplant access remain scarce locally and are expensive — highlighting the need for prevention.
- Occupational health interventions: workplace water and rest breaks, shade, and heat-stress mitigation for field workers. These interventions are low-cost and effective in heat-related nephropathy elsewhere.
Public health and policy responses — what works
Because the causes are likely multi-layered, response must be comprehensive:
- Primary prevention (workplace): Provide potable water, scheduled rest in shade, and protective policies for outdoor workers during hot months. These measures are central to preventing heat-related AKI.
- Community screening & surveillance: Routine CKD screening in hotspots to detect early disease and monitor trends.
- Water safety & environmental monitoring: Regular testing of groundwater and mitigation if contaminants are found.
- Research & data systems: Continued epidemiologic, occupational, genetic and exposure studies (ICMR and university projects), plus registries to track outcomes.
- Socioeconomic support: Financial help for patients with advanced CKD, transport for dialysis, and public insurance coverage to reduce catastrophic health expenditure.
These multipronged interventions are the most pragmatic route to reduce incidence and mortality while research continues to identify specific etiologic agents.
Unresolved questions and research priorities
Key gaps remain that urgent research should address:
- Causal attribution: robust longitudinal cohort studies with individual exposure assessment (heat metrics, hydration, specific agrochemicals, water chemistry and biomarkers of exposure) are needed.
- Mechanisms: how repeated mild AKI evolves into chronic interstitial fibrosis across diverse exposures (heat + toxin interactions).
- Intervention trials: randomized or well-designed implementation trials testing workplace hydration, cooling, and reduced exposure to candidate toxins to see if CKD incidence falls.
- Health systems research: how to scale screening, dialysis, and transplantation equitably in affected rural regions.
Addressing these gaps requires collaboration across nephrology, occupational medicine, environmental sciences, public health and local communities.
Lessons from elsewhere — what Sri Lanka and Central America teach us
Comparing Uddanam to Sri Lankan and Mesoamerican CKDu hotspots is instructive: all three share agricultural contexts, heat exposure, and tubulo-interstitial pathology, suggesting converging etiologic themes. However, each hotspot has local modifiers (different crops, water chemistry, social structures) demonstrating that no single global explanation suffices and local, tailored solutions are necessary.
Practical recommendations for clinicians working in or near Uddanam
- Maintain a high index of suspicion in agricultural workers with low urine output, unexplained fatigue, or mild kidney function decline.
- Early screening using eGFR and urine tests in at-risk populations.
- Counsel on heat stress prevention: frequent sips of water, rest, and avoidance of NSAIDs during heat work.
- Avoid unnecessary nephrotoxins including certain traditional herbal remedies unless proven safe.
- Refer early for nephrology assessment when eGFR falls or for persistent abnormalities.
- Community engagement: work with local health workers to promote workplace hydration and education.
Conclusion — a call to action
Uddanam nephropathy is a major, persistent public-health problem characterised by a high burden of CKD among agricultural communities with unclear, likely multifactorial causes. The strongest current evidence implicates occupational heat stress and repeated subclinical kidney injury, interacting with environmental exposures, social determinants and individual susceptibility. While scientists continue searching for definitive causative agents, there is a compelling and immediate mandate for primary prevention (better workplace hydration and heat mitigation), community screening, and strengthening local health systems to manage CKD early and humanely.
Integrated care at the Institute of Urology, Jaipur
Patients from Uddanam and other CKD-affected regions often need multidisciplinary urological and nephrological care — from diagnosis and renal-protective counselling to management of urinary complications and access to surgical options. At the Institute of Urology, Jaipur, we deliver integrated services under one roof: outpatient consultation, diagnostic imaging, laboratory investigations, and surgical interventions when required.
Our centre combines clinical excellence with compassion. Senior urologists Dr. M. Roychowdhury and Dr. Rajan Bansal lead a team experienced in managing the full spectrum of urological conditions — including complications related to chronic kidney disease, urinary stone disease, prostate disorders, and paediatric urology. The Institute’s coordinated approach ensures patients receive timely diagnostics, evidence-based management, and seamless access to allied services (nephrology referrals, dialysis linkages and surgical care) — a model that matters in regions where CKD imposes high human and economic costs.
Selected key references
(Representative recent and high-impact studies and reviews; please format to your journal’s reference style.)
- Tatapudi RR, et al. High Prevalence of CKD of Unknown Etiology in Uddanam, Andhra Pradesh, India. Indian J Nephrol / PLOS/PMC report. 2018.
- Gummidi B, et al. A Systematic Study of the Prevalence and Risk Factors of CKD in Uddanam. 2020.
- Johnson RJ, et al. Chronic Kidney Disease of Unknown Cause in Agricultural Communities (NEJM Review). 2019.
- Weaver VM, et al. Global dimensions of CKDu: hotspots in Sri Lanka, Central America and India. 2015.
- Lal K, et al. Assessment of Groundwater Quality of CKDu-Affected Uddanam Region. Groundwater Sustain Develop. 2020.
- Farag YMK, et al. Occupational risk factors for CKD in Andhra Pradesh: Uddanam Nephropathy. Renal Failure. 2020.
- John O, et al. Chronic Kidney Disease of Unknown Etiology in India — review. Kidney Int Reports / KIDNEY reports 2021.
- Latest regional and policy reports and news coverage (Andhra Pradesh CKD screening, 2024–2025 pilot studies).
