The genetics of kidney stone disease and nephrocalcinosis

Abstract

Kidney stones (also known as urinary stones or nephrolithiasis) are highly prevalent, affecting approximately 10% of adults worldwide, and the incidence of stone disease is increasing. Kidney stone formation results from an imbalance of inhibitors and promoters of crystallization, and calcium-containing calculi account for over 80% of stones. In most patients, the underlying aetiology is thought to be multifactorial, with environmental, dietary, hormonal and genetic components. The advent of high-throughput sequencing techniques has enabled a monogenic cause of kidney stones to be identified in up to 30% of children and 10% of adults who form stones, with ~35 different genes implicated. In addition, genome-wide association studies have implicated a series of genes involved in renal tubular handling of lithogenic substrates and of inhibitors of crystallization in stone disease in the general population. Such findings will likely lead to the identification of additional treatment targets involving underlying enzymatic or protein defects, including but not limited to those that alter urinary biochemistry.