Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go

John, Oommen; Gummudi, Balaji; Jha, Anubhuti; Gopalakrishnan, Natarajan; Kalra, Om Prakash; Kaur, Prabhdeep; Kher, Vijay; Kumar, Vivek; Machiraju, Ravi Shankar; Osborne, Nicholas J.; Palo, Subrata Kumar; Parameswaran, Sreejith; Prasad, Narayan; Rathore, Vinay; Rajapurkar, Mohan; Sahay, Manisha; Tatapudi, Ravi Raju; Thakur, Jarnail Singh; Venugopal, Vidhya; Jha, Vivekanand

doi:10.1016/j.ekir.2021.07.031

Cited by 35 publications

(27 citation statements)

References 35 publications

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“…showed more than 70% CKDu patients in Odisha belonged to lower socioeconomic groups, and 48% were engaged in agricultural activities. 5 The prevalence of CKD was equal in the two sexes. The prevalence was ≥20% in one-third of the sampled villages, suggesting geographic clustering.…”

Section: Discussionmentioning

confidence: 98%

“…Narasinghpur and Badamba blocks in the Cuttack district are regarded by the local press as hotspots. 5 Chronic kidney disease of unknown origin (CKDu) in Odisha contributes significantly to the national burden of CKD in India. Most of the affected persons are from the productive age group.…”

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confidence: 99%

“…The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. 5 Different etiologies which have been proposed for causing CKDu are heavy metals, pesticides, infections, local brand alcohol consumption, genetic factors, heat exposure, and nephrotoxic drugs. MeN was mostly seen in the poor young male sugarcane cultivators who used to work in the hot and humid climate for long hours.…”

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confidence: 99%

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Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha

Parida¹,

Das²,

Kar³

et al. 2022

JAPI

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Introduction: Chronic kidney disease (CKD) is emerging as a serious health problem in Odisha, India. A new form of severe CKD affecting adults, not due to traditional risk factors like diabetes, hypertension, glomerulonephritis, has been reported in Sri Lanka, Central America, and Egypt in the last two decades. This has been named CKD of unknown origin (CKDu), and it is fatal due to late recognition and rapid disease progression. The aim of the study was to elucidate the association between different sociodemographic, and biochemical parameters with renal morphology in CKD of unknown origin patients. Methods: A cross-sectional study was conducted on 124 consecutive patients with CKD from the period January 2018 to December 2018. Patients in the age group 18–60 years who met clinical criteria for CKD were included. Participants answered a questionnaire. After the necessary history, clinical evaluation, and blood and urine analyses, a kidney biopsy was undertaken. Kidney biopsy was feasible in 51 patients as the rest 61 patients had shrunken kidneys and 12 patients did not give consent. Patients with diabetes mellitus (DM), hypertension, glomerulonephritis, polycystic kidney disease, obstructive kidney disease or any other congenital diseases, snakebite, pregnancy, malignancy, gout, primary hyperparathyroidism, infectious diseases like human immunodeficiency virus (HIV), TB, Hepatitis B and C, malaria, syphilis, leprosy and coagulopathies were excluded. Among the 51 patients, 23 had CKDu, 25 had chronic glomerulonephritis and three biopsies were inconclusive. Results: The mean age of CKDu patients was 36.78 ± 9.85 years. Males (73.9%) were predominantly affected. A family history of CKD was seen in 82.6% of CKDu cases. Hyponatremia and hypokalemia were predominant biochemical abnormalities in our CKDu cases. Binary logistic regression showed rural residence, family history of CKD, exposure to smoke from burning coal, charcoal, or biomass fuels, low socioeconomic status, and low body mass index were strongly associated with CKDu. There was an increased risk of developing CKDu in persons with a family history of CKD [p = 0.003, odds ratio (OR)— 17.58], persons exposed to smoke from burning coal, charcoal or biomass fuels (p = 0.003, OR- 32.4), and patients with low socio-economic status (p = 0.001, OR- 15.87). Interstitial fibrosis (IF), interstitial inflammation with mononuclear infiltration, tubular atrophy (TA), and global glomerulosclerosis (GS) were pertinent histopathological findings in our study. Conclusion: There is no strong evidence for a single cause for CKDu, and multiple environmental, occupational and social factors are probably involved. We need to design consistent and comparative multisite studies to identify etiologies of CKDu, across high-risk populations that may help elucidate the importance of region-specific vs global risk factors.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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confidence: 99%

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Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha

Parida¹,

Das²,

Kar³

et al. 2022

JAPI

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“…In India, lead, fluoride, and chromium have been identified variably in blood or urine samples of CKDu patients [7 ▪ ,33]. Groundwater silica levels are up to eight-fold higher in endemic vs. nonendemic regions reaching 12 times higher than recommended levels [7 ▪ ,36]. It should be noted that not all studies have found correlations with nephrotoxin exposure and CKDu; thus, a definitive role in disease initiation or progression has not been proven.…”

Section: Pathogenesismentioning

confidence: 99%

Chronic kidney disease with unknown cause across the global spectrum

Nast

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewIn the 1990s, a type of chronic kidney disease with unknown cause (CKDu) was identified in Central America and Sri Lanka. Patients lacked hypertension, diabetes, glomerulonephritis, or other usual causes of kidney failure. Affected patients are predominantly male agricultural workers aged 20--60 years, living in economically disadvantaged areas with poor access to medical care. Patients typically present late and progress to end-stage kidney disease within 5 years, resulting in social and economic hardship for families, regions, and countries. This review covers the current state of knowledge for this disease. Recent findingsThe prevalence of CKDu is increasing in known endemic regions and across the globe, reaching epidemic proportions. There is primary tubulointerstitial injury with secondary glomerular and vascular sclerosis. No definitive etiologic factors have been identified, and these may vary or overlap in different geographic locations. The leading hypotheses include exposure to agrochemicals, heavy metals and trace elements, and kidney injury from dehydration/heat stress. Infections and lifestyle factors may play a role, but are likely not key. Genetic and epigenetic factors are beginning to be explored. SummaryCKDu is a leading cause of premature death in young-to-middle-aged adults in endemic regions and has become a public health crisis. Studies are underway to investigate clinical, exposome, and omics factors, and hopefully will provide insights into pathogenetic mechanisms resulting in biomarker discovery, preventive measures, and therapeutics.

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“…Chronic kidney disease with unknown cause (CKDu) has recently been reported in people from poor communities in Mesoamerica [4], Sri Lanka [5,6], and India [7,8]. Initially, CKDu was suspected to be an occupational disease associated with exposures in the agricultural workplace, such as heat stress and dehydration [4], pesticide spraying [9], heavy metals and agrochemicals [10], or the use of NSAIDs [11].…”

Section: Introductionmentioning

confidence: 99%

Association of Pesticides and Kidney Function among Adults in the US Population 2001–2010

Wan

Darssan

Karatela

et al. 2021

IJERPH

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Chronic kidney disease of unknown cause is prevalent in a range of communities; however, its etiology remains unclear. We examined the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway. We pooled data from four cross-sectional waves of NHANES, with 41,847 participants in total. Exposure to malathion increased the risk of low kidney function (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Increased risk of low kidney function was not found among those exposed to 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12), and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13). Our findings provide evidence of altered kidney function in people exposed to malathion, highlighting the potential of organophosphate pesticides’ role in renal injury.

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Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go

Cited by 35 publications

References 35 publications

Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha

Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha

Chronic kidney disease with unknown cause across the global spectrum

Association of Pesticides and Kidney Function among Adults in the US Population 2001–2010

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