Introduction:
There is an alarming increase in the incidence of a chronic kidney disease of unknown etiology (CKDu) that primarily affects young, economically active workers engaged in agricultural activities in Mesoamerica and South Asia. Despite extensive research over the past two decades, the causes of CKDu remain unclear. The disease is characterized by progressive loss of renal function with minimal or no proteinuria and hematuria. The CURE Consortium is a cooperative network with the following goals: (i) to identify causes of decline in kidney function, (ii) to better characterize the clinical phenotypes of individuals with CKDu and differentiate them from other forms of CKD, (iii) to employ advanced laboratory and data analysis methods to conduct discovery science related to risk factors, biological markers, and causal mechanisms; and (iv) to establish a biorepository for future research.
Methods:
The CURE study is a prospective cohort study aiming to enroll 3,600 participants, with two-thirds from sites in Central America and one-third from India. Eligible individuals must be aged 18-45 years with eGFR ≥ 30 ml /min/1.73m2 as determined at local laboratories, have no evidence of diabetes by structured interview and hemoglobin A1c level, and no other known causes of CKD. The enrollment plan aims for proportional representation across three eGFR categories (30-59, 60-89, ≥90 mL/min/1.73m2). Based on the sex difference in CKDu prevalence across study regions, the study targets enrolling at ≥80% men in Mesoamerica and ≥60% men in India within each eGFR stratum. To ensure a balanced age distribution, each eGFR stratum have no more than two thirds of participants aged either 18-30 or 31-45 years. Individuals will have 4 visits at eight-month intervals. Biological samples and environmental samples are collected following standard procedures. REDCap questionnaires capture data on family structure, demographics, medical history, recent medical visits, medication use, occupational and environmental exposures, diet, and alcohol and tobacco use. Serum, plasma, whole blood, and urine will be collected, locally processed, and shipped to a biorepository in the United States for CLIA-certified laboratory assays, including IDMS-traceable creatinine assays to establish baseline eGFR, kidney function biomarkers, pathogens, trace elements, untargeted metabolomics, and genetic assays. Environmental samples will be collected from a subset of study participants analyzed for trace elements, agrochemicals, and burning exposures. The statistical plan aims to identify risk factors for CKDu, including complex relationships and interactions, while controlling for confounders. Associations between individual risk factors and each of the study outcomes will be estimated using models that include a single risk factor as the exposure, with appropriate controls, as well as mixture models.
Results:
Conclusions:
Implementing a prospective cohort study across multiple sites requires the involvement of investigators across diverse areas of expertise and local stakeholders. The findings will help identify exposures to address through targeted workplace or community interventions.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.