Uddanam Nephropathy/Regional Nephropathy in India: Preliminary Findings and a Plea for Further Research.

Address correspondence to Anirban Ganguli, MD, Washington Hospital Center, 110 Irving St NW, Ste 2A70, Washington DC 20010. E-mail: [email protected] 2016 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2016.04.012 Even as chronic kidney disease (CKD) emerges as a global health problem, resource-constrained nations struggle to address this challenge due to the significant cost of life-sustaining long-term renal replacement therapies. Recently, investigators in Central America, Southern Asia, and Egypt have reported a form of CKD among poor agricultural working communities not attributable to traditional causes such as diabetes, hypertension, primary glomerular disease, or obstructive nephropathy. Based on the geographic areas of primary reporting, it has been called Central American nephropathy, chronic tubulointerstitial kidney disease of Central America, Mesoamerican nephropathy (MeN), Salvadoran agricultural nephropathy, Sri Lankan agricultural nephropathy, and Udhanam endemic nephropathy (India). This wave of CKD is distinct from previously reported regional nephropathies such as Balkan nephropathy, for which specific environmental causes are believed to have been identified. Table 1 summarizes some of the features of this new wave of regional nephropathies typically reported from hot, low-altitude, coastal or subcostal, tropical, and subtropical regions of the world. There is no universally accepted definition for this clinical entity. Although Sri Lankan studies have defined it on the basis of persistent urine albumin-creatinine ratio $ 30 mg/g (but excluding glomerular proteinuria) in the absence of known causes of CKD or severe hypertension, a consensus definition of MeN was recently published incorporating the standard 2012 KDIGO (Kidney Disease: Improving Global Outcomes) definition of CKD when applied to inexplicable cases of CKD originating in Central America. Notwithstanding these differences, similarities in disease patterns include late presentation, a long asymptomatic phase, nonglomerular proteinuria, and the absence of hypertension in early phases of the disease prior to reduction in glomerular filtration rate, features that are typical of chronic tubulointerstitial disease and that have been validated through urinary biomarkers and renal histopathologic studies in some cases. The disease appears to be more common in young male agricultural workers. Although certain occupations are clearly at risk (Table 1), genetic susceptibility may also be contributory, given an association of cases with family history of CKD and disease linkage with single-nucleotide polymorphisms in the SLC13A3 and KCNA10 genes, as in Sri Lankan nephropathy.