Water sources and kidney function: investigating chronic kidney disease of unknown etiology in a prospective study

Chaoran Hu,Lalarukh Haider,Tudor Silva,Jean J Schensul,Penny Vlahos,Nishantha Nanayakkara,Rohana Chandrajith,Saranga Diyabalanage,Pasan Hewavitharane,Shuchi Anand,Allison Staniec,Emma Shipley,Stephen L Schensul,Toan Ha

doi:10.1038/s41545-021-00141-2

Abstract

A chronic Kidney Disease of unknown etiology (CKDu) has emerged with disproportionately high prevalence across dry lowland agricultural communities globally. Here we present the results of a prospective cohort of 293 patients with CKDu in the endemic region of Wilgamuwa, Sri Lanka, in whom we measured baseline kidney function and undertook quarterly follow up over 2 years. Well water was the primary historic drinking water source in the region, although a majority (68%) of participants reported switching to reverse osmosis water during study follow ups. Participants who reported ever drinking from well water had estimated glomerular filtration rates −6.7 (SD: 2.8) ml/min/1.73 m2 lower than participants who did not drink from well water historically (p = 0.0184) during the study period. Geospatial analysis identifies a cluster within the region where CKDu progression is significantly higher than the surrounding area. Samples of household wells (n = 262) indicated 68% had detectable agrochemical compounds with concentration above global water quality standards. It is expected that the detected contaminants compounds are indicators of poor water quality and that there is likely additional agrochemical exposure including commercial additives that may contribute to CKDu onset and/or progression. Thus, our study finds that well water exposure during a person’s lifetime in this region is associated with kidney function decline and identifies and quantifies putative nephrotoxic agrochemicals above safe drinking water concentrations in these wells.

Highlights

The rising global death toll from chronic kidney disease (CKD), the world’s 12th leading cause of death, is considered a downstream consequence of the growing global prevalence of diabetes (4.7% of adults in 1980 and 8.5% in 2014) and hypertension (31.1% among adults, 90% increase from 1975–2015)[1,2]
There has been a rapid increase in a “non-traditional” type of CKD in rural lowland agricultural communities that is not associated with uncontrolled diabetes and hypertension, termed chronic kidney disease of “unknown etiology” (CKDu) in South Asia[3], known as Mesoamerican Nephropathy (MeN) in Central and South America[4] and the Central Valley of California[5]
This paper examines the association between water source contamination and kidney function decline, drawing on data from the Kidney Progression Project (KiPP)[13], a Sri Lanka-US collaboration of geochemists, anthropologists, and nephrologists, funded by the Fogarty International Center of the US National Institutes of Health

Summary

Introduction

The rising global death toll from chronic kidney disease (CKD), the world’s 12th leading cause of death, is considered a downstream consequence of the growing global prevalence of diabetes (4.7% of adults in 1980 and 8.5% in 2014) and hypertension (31.1% among adults, 90% increase from 1975–2015)[1,2]. While a majority of CKD is characterized as a primarily glomerular disease[3,4], CKDu is a tubulointerstitial disease with varying degrees of interstitial fibrosis, interstitial inflammation, and tubular atrophy[3,5]. Both types move inevitably toward kidney failure and death unless there is intervention through hemodialysis or a kidney transplant.

Methods

Results

Conclusion