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

Background: Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of 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 hypothesis whether heavy metals i.e. Arsenic (As), Cadmium (Cd), Lead (Pb) and Chromium (Cr) are associated with CKDu, in central India. Methods: The study was conducted in 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. Pesticides use, pain killers, smoking and alcohol addiction were also evaluated. The median levels of blood and urine metals were compared among the groups by Kruskal-Wallis rank sum test. Result: CKDu had significantly higher pesticide use. 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). Urine Cd was higher in CKD 1.0 (0.3–1.7) µg/L compared to CKDu 0.5 (0.0-1.5) µg/L with a trend (p-0.06) of significance. Blood and urinary Pb and Cr were higher in CKD compared to CKDu (P = 0.5). 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). Conclusion: The study showed a significant association of As with CKDu and a trend of association of Cd with CKD in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) have significantly higher metal burden of Pb, Cd, As, Cr as comparedto healthy controls.