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.

Kidney stone disease: pathophysiology, investigation and medical treatment

“…If distal renal tubular acidosis (dRTA) is identified, 28,29 an underlying cause should be sought. Calcium phosphate stones are a feature of many rare monogenic diseases 30 including inherited forms of dRTA and the X-linked condition, Dent's disease.…”

Reduced albumin in the renal cortex of ethylene glycol-treated rats

“…Albumin, for example, may play a role as an inhibitor to decrease stone formation 2 . However, some urinary proteins may also promote stone formation 3 . Recently, we isolated albumin from calcium oxalate (CaOx) stones and found that albumin can induce CaOx nucleation.…”

The Search for Monogenic Causes of Kidney Stones

“…Acupuncture down-regulated the genes involved in muscle breakdown (atrogin-1 and muscle RING-finger protein-1) and upregulated Akt1 and Transient receptor potential cation channel subfamily V member 4, which are positive regulators of protein synthesis. In another study, Takaoka et al 6 demonstrated that electroacupuncture treatment induced satellite cell proliferation in nonatrophic skeletal muscle through the suppression of myostatin expression.…”

“…6 The study by Halbritter et al in this issue of JASN is therefore welcome in suggesting that perhaps a larger proportion of symptomatic stones are in fact the result of known, single-gene disorders. 7 The study did not, by intent, attempt to reveal new genetic contributors to kidney stones.…”