Pediatric kidney health outcomes in communities impacted by chronic kidney disease of unknown etiology (CKDu): a systematic review.

backgroundChronic 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.

objectivesTo systematically uncover and understand international studies of kidney health among children living in CKDu-endemic areas or with CKDu-related exposures. DATA SOURCES: A systematic literature search was conducted in six databases and included a mix of keywords and subject headings representing chronic kidney disease of unknown etiology, Mesoamerican nephropathy, chronic interstitial nephritis of agricultural communities, chronic kidney disease, agriculture, farm, and pediatrics. STUDY ELIGIBILITY CRITERIA: Articles were included if they reported kidney health outcomes of pediatric populations living in proximity to CKDu-affected areas or with a CKDu-relevant exposure. There were no limitations on geography or study design. STUDY APPRAISAL AND SYNTHESIS

methodsMultiple authors performed study screening and data extraction. Quality assessment was performed using the Appraisal Tool for Cross-Sectional Studies (AXIS) or the JBI Critical Appraisal Tool for Cohort Studies based on the study design. Each article's strengths and limitations are summarized narratively.

resultsWe screened over 1800 abstracts and included twenty-nine peer-reviewed publications from nine different countries. The most common study design involved cross-sectional analysis of biological specimens from children in an established CKDu-endemic area. Prevalence of albuminuria and decreased estimated glomerular filtration rates differed widely between countries. Novel urinary biomarkers frequently demonstrated subclinical kidney damage, although the specific biomarker(s) varied between studies. Despite heterogeneous 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. LIMITATIONS: The limitations of our review include the heterogeneous nomenclature of CKDu and dependence on authors' awareness of this emerging disease. The included studies were heterogenous in the reported outcomes precluding direct comparisons of key metrics and meta-analysis. CONCLUSIONS AND IMPLICATIONS OF KEY

findingsOur analysis 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. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ID CRD42023394987.