The dilemma of chronic kidney disease of unknown origin

Abstract

Over the past two decades, cumulative increases in the prevalence of chronic kidney disease (CKD) have been observed in selected geographic areas in several countries. The etiology of this CKD cannot be attributed to known or traditional causes or risk factors, and the term chronic kidney disease of unknown etiology (CKDu) has been used to describe this entity. These regional endemic nephropathies are commonly known as CKD of unidentified cause (CKDu) or CKD of nontraditional etiology (CKDnt) and, more recently, Chronic interstitial nephritis of agricultural communities (CINAC). Unlike the traditional causes of CKD (i.e., Hypertension, Diabetes, chronic glomerulonephritis, etc), CKDu has been associated with agricultural and arid regions. Also, the socioeconomic state of those regions is key. This review addresses the present status of the knowledge for different aspects of this regional health problem as well as summarizes available evidence on the risk factors, epidemiology, clinical features, diagnosis, treatment, and prevention of CKDu. It will also highlight the reasons why Africa should be concerned about this condition. Using the keywords “Africa, CKD of unknown origin,” a literature search was conducted on PubMed, Scopus, and Google Scholar, focusing on the research published between 2000 and 2022. Results from the literature show that predisposition to heat stress and dehydration, subclinical rhabdomyolysis, toxins from alcoholic beverages, agrochemicals, and heavy metals all result in acute kidney injury, and repeated exposures to these factors can then cause CKDu. Earlier studies in Sri Lanka nephropathy by Nanayakkara and his team in 2014 identified that a genetic variant of SLC13A3 (sodium-dependent dicarboxylate transporter member 3) is associated with CKDu. Later research conducted in 2015 discovered KCNA10 (a voltage-gated potassium channel) also as a gene implicated in CKDu; these genetic variances were discovered to be common among the populace suffering from kidney diseases, hence suggesting that, people with these genes have a high risk of developing kidney disease. Predisposition to heat stress and dehydration, subclinical rhabdomyolysis, and toxins from alcoholic beverages, agrochemicals, and heavy metals all results in acute kidney injury, and repeated exposures to these factors can then cause CKDu. Also, certain genes have been found to be associated with CKDu.