Rationale and Design of the International Prospective Study of CKD of Uncertain Etiology in Agricultural Communities

There has been an alarming increase in the incidence of a chronic kidney disease (CKD) of unknown etiology primarily affecting young individuals engaged in agricultural activities in Mesoamerica and South Asia. Despite extensive research over the past 2 decades, causes remain unclear. The disease is characterized by progressive loss of kidney function with the absence of heavy proteinuria and hematuria. The International Prospective Study of CKD of Unknown Etiology in Agricultural Communities (CURE study) aims to do the following: (i) identify factors associated with kidney function decline among individuals with or at risk for CKD of uncertain etiology (CKDu); (ii) better characterize the clinical phenotypes of individuals with CKDu and differentiate them from other forms of CKD; (iii) employ advanced laboratory and data analysis methods to conduct discovery science related to risk factors, biomarkers, and causal mechanisms; and (iv) establish a biorepository for future research.

The CURE study is a prospective cohort study of up to 3600 participants from 7 sites in Central America and India aged 18 to 45 years with estimated glomerular filtration rate (eGFR) ≥ 20 ml/min per 1.73 m², no evidence of diabetes, and no other known causes of CKD. Biological samples and questionnaire data are collected from participants during 4 visits at 8-month intervals.

Blood, urine, and hair will be analyzed for kidney function biomarkers, trace elements, pesticides and other contaminants, untargeted metabolomics, and genetic assays. Environmental samples, collected from a subset of study participants, will be analyzed for trace elements, agrochemicals, and burning exposures.

This study will provide novel information about CKDu etiology and clinical phenotypes across distinct geographies.