Pediatric Kidney Injury in Communities Impacted by Chronic Kidney Disease of Unknown Etiology (CKDu): A Comprehensive Systematic Review of Epidemiologic Studies

Background: Chronic kidney disease of unknown etiology (CKDu) is a tubulointerstitial disease that disproportionately affects young, primarily male, agricultural workers in Mesoamerica and South Asia who lack traditional risk factors for kidney disease. Extensive research in adult populations suggests the etiology is complex and indicates that early childhood exposures could have an integral role. Objectives: To identify, summarize, and compare research in children living in CKDu endemic areas or with relevant CKDu-related exposures. Methods: A systematic literature search was conducted in six databases for studies that report kidney health outcomes of pediatric populations living in proximity to CKDu-affected areas with no limitations on geography or study design. Studies were independently screened for inclusion and underwent quality assessment using the Appraisal Tool for Cross-Sectional Studies (AXIS) or the JBI Critical Appraisal Tool for Cohort Studies based on the study design by at least two authors. Data are compared narratively and graphically. Results: We included twenty peer-reviewed publications and two meeting abstracts from eight different countries. The most common study design involved cross-sectional analysis of biological specimens from children in an established CKDu endemic area. Marked decreases in estimated glomerular filtration rate were generally not identified and prevalence of albuminuria differed widely between countries. Novel urinary biomarkers frequently demonstrated subclinical kidney damage, although the specific biomarker(s) varied between studies. Epidemiologic factors associated with evidence of subclinical kidney damage in children included proximity to agriculture or agrichemicals. Despite heterogenous study outcomes, all studies concluded that there were signs of kidney injury in children living in CKDu endemic areas or with a CKDu-relevant environmental exposure. Conclusion: This systematic review suggests that the pathophysiologic process leading to CKDu may begin prior to adulthood. Future longitudinal research aimed at elucidating the multifaceted factors and exposures impacting entire communities, including children, is imperative for disease prevention strategies.