Genetics of hypercalciuric stone forming diseases

Abstract

With a lifetime incidence of up to 12% in man and 6% in woman, nephrolithiasis is a major health problem worldwide. Approximately, 80% of kidney stones are composed of calcium and hypercalciuria is found in up to 40% of stone-formers. Although the mechanisms resulting in precipitation and growth of calcium crystals in the urinary tract are multiple and not fully understood, hypercalciuria per se is recognized as an important and reversible risk factor in stone formation. In this brief review, we summarize the studies assessing the heritability of hypercalciuria and pinpoint recently identified human genetic disorders as well as relevant animal models that provided new insights into the segment-specific tubular handling of calcium and the pathophysiology of renal hypercalciuria and kidney stones. We also discuss novel strategies that may help to unravel the genetic bases of such complex conditions.