Systematic Review of Kidney Injury Biomarkers for the Evaluation of CKD of Uncertain Etiology

Introduction: Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions. Methods: We conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). The literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included "CKDu," "Mesoamerican Nephropathy," "CKD of unknown etiology," "Chronic Interstitial Nephritis in Agricultural Communities," "biomarker," "urin*," and/or "plasma." Results: A total of 25 papers were included. The 2 most frequently measured biomarkers were urinary kidney injury molecule-1 (KIM -1) and urinary neutrophil gelatinase-associated lipocalin (NGAL). There was substantial variability in study design, laboratory assay methods, and statistical methodology, which prohibited meta-analysis. Conclusion: Biomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.