PNPLA3 gene and kidney disease

Abstract

Chronic kidney disease (CKD) is a disease regularly seen in clinical practice. At present, CKD is described as a change of kidney structure and/or function and it is classified in relation to cause, values of glomerular filtration rate and albuminuria category. Seeing that CKD is closely linked to the development of end-stage renal disease and other comorbidities, the determination of additional independent predictors for CKD is clinically necessary. At present, there is evidence associating non-alcoholic fatty liver disease (NAFLD) with CKD, thereby suggesting that NAFLD patients may require intensive surveillance to reduce their risk of CKD. In 2008, genome-wide association studies documented an association between the variant rs738409 (C > G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene (mainly implicated in the lipid regulation) and the entire spectrum of NAFLD (i.e., liver steatosis, non-alcoholic steatohepatitis, fibrosis, and hepatocellular carcinoma). In the last years, accumulating epidemiological evidence suggests the existence of a relationship between PNPLA3 rs738409 and risk of CKD, indicating that rs738409 may also contribute to the kidney injury. This is of particular scientific interest, as such association may explain, at least in part, the epidemiological association between liver and kidney disease. In this narrative review, we will discuss the accumulating evidence regarding the association between PNPLA3 rs738409 and risk of CKD, the putative biological mechanisms underpinning such relationship, and the possible future perspective.

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