Genetics and calcium nephrolithiasis

Abstract

Calcium nephrolithiasis is one of the most prevalent uronephrologic disorders in the western countries. Studies in families and twins evidenced a genetic predisposition to calcium nephrolithiasis. Family-based or case-control studies of single-candidate genes evidenced the possible involvement of calcium-sensing receptor (CASR), vitamin D receptor (VDR), and osteopontin (OPN) gene polymorphisms in stone formation. The only high-throughput genome-wide association study identified claudin 14 (CLDN14) gene as a possible major gene of nephrolithiasis. Specific phenotypes were related with these genes: CASR gene in normocitraturic patients, VDR gene in hypocitraturic patients with severe clinical course, and CLDN14 gene in hypercalciuric patients. The pathogenetic weight of these genes remains unclear, but an alteration of their expression may occur in stone formers. Technological skills, accurate clinical examination, and a detailed phenotype description are the basis to get new insight about the genetic basis of nephrolithiasis.