Factors Associated with Chronic Kidney Disease of Unknown Etiology (CKDu): A Systematic Review

Abstract

(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.

Exposome and Metabolome Analysis of Sugarcane Workers Reveals Predictors of Kidney Injury

“…Exposure to heavy metals has long been known to cause renal damage and is suspected of playing a key role in recent epidemics of kidney injury, due to use of agrochemicals known to contain nephrotoxic metals and some evidence of elevated heavy metal levels in agricultural communities’ water sources. 21 , 45 , 46 , 47 , 48 , 49 Indeed, arsenic, cadmium, and lead are pervasive toxicants with established mechanisms for inducing both acute kidney injury and CKD, resulting in ongoing investigations into potential contributions to the epidemics of CKDu occurring worldwide. 50 , 51 Although some association of heavy metals have been made with increased risk of CKDu, such findings have been inconsistent.…”

Factor Associated of Chronic Kidney Disease of Uncertain Etiology: A Comprehensive Systematic Review

“…For instance, many authors limit CKDu to a particular type of CKD frequently found in rural settings in non-diabetic people, accompanied by low-grade proteinuria, and a rapid transition to end-stage kidney disease (ESKD). 4,5 The atypical presentation of CKDu has become epidemic in different regions of the world, which usually remains undiagnosed until its late stage. Over the past few decades, parts of Central America, South Asia, Eastern Europe, and other countries such as Sudan, Tunisia, Tanzania, and the El-Minia Governorate in Egypt reported a similar disease pattern.…”

“…Subsequently, a similar endemic was also reported, such as Balkan endemic nephropathy, Mesoamerican nephropathy, and Chinese herb nephropathy, which were named after the area of origin. 4…”

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

“…Potential causes include environmental or occupational exposure to nephrotoxins, heat stress, infection, and genetic predisposition. 6 , 7 , 8 The disease typically affects individuals younger than 50 years, men, and those who engage in strenuous manual labor; several regions, particularly in India and Sri Lanka, report similar disease rates in women. CKDu—or a similar disease process—can also occur in nonagricultural communities.…”