Swetalina Nayak

(1) Background: Despite ample research, the factors, specific causes, and pathways associated with chronic kidney disease of unknown etiology (CKDu) remain elusive. Therefore, we performed a systematic review to explore the potential etiologies for the development of CKDu globally. (2) Methods: A systematic literature review was conducted using databases CINAHL, Cochrane Library, Embase, Google Scholar, MEDLINE, and PsycINFO on the specific causes and pathophysiology related to CKDu from inception until April 2021. Study selection, data extraction of included articles, and quality appraisal were assessed. The narrative approach was used to summarize and comprehend the findings. (3) Results: Our study included 25 studies, considering 38,351 participants. Twelve studies were case–control, ten were cross-sectional, and three were cohort designs. All articles were from low-and middle-income countries (LMICs). The findings suggest 12 factors are associated with CKDu. Most studies (n = 8) identified farming and water sources as the factors related to CKDu, with heavy metal toxicity coming in second (n = 7). (4) Conclusion: The systematic review reported various factors associated with CKDu, from which most studies reported farming, water sources, and heavy metal poisoning. Considering the findings, the study recommends future strategies and public health initiatives to prevent the epidemiological/environmental factors contributing to CKDu.