Meso-American nephropathy: what we have learned about the potential genetic influence on chronic kidney disease development

Chronic kidney disease of unknown aetiology (CKDu) refers to the epidemic level of incidence of CKD in several low- and middle-income countries, usually near the equator, for which the aetiology has not been identified. CKDu represents a form of CKD hotspot, defined as a country, region, community or ethnicity with a higher than average incidence of CKD. In terms of the number of persons affected, the so-called hypertensive nephropathy of African Americans probably represents the largest CKD hotspot, which is largely driven by variants of the APOL1 gene, questioning the very existence of hypertensive nephropathy and illustrating how kidney disease driven by genetic predisposition may underlie some forms of hypertension. For CKDu, hard physical work leading to dehydration (the first global warming-related disease?) and local toxins are leading aetiological candidates. Meso-American nephropathy is probably the best-characterized CKDu. In this issue of CKJ, a systematic review and meta-analysis by Gonzalez et al. identified positive associations between Meso-American nephropathy and male gender, family history of CKD, high water intake and lowland altitude. We now discuss the potential relationship of family history to genetic predisposition and how a better understanding of CKDu may help advance the aetiological characterization of the nearly 50% of end-stage renal disease patients worldwide that have no known cause for CKD or have been assigned non-specific diagnoses.