What is the role of genetics in the etiology of nephrolithiasis?

Updated: Jan 13, 2020
  • Author: Chirag N Dave, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Nephrolithiasis is known to have a familial nature and significant heritability, and genes that may be involved in renal stone formation have been identified. Genome-wide association studies and candidate gene studies have implicated genes involved in renal tubular handling of lithogenic substrates, such as calcium, oxalate, and phosphate, and of inhibitors of crystallization, such as citrate and magnesium. [13]

Using whole-exome sequencing, Daga et al detected monogenic causative mutations in 15 of 51 families with members who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis. Identified mutations were in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), one dominant gene (SLC9A3R1), and one gene (SLC34A1) with both recessive and dominant inheritance. [14]

In patients with idiopathic hypercalciuria and calcium-containing kidney stones, genetic screens of nephrolithiasis determinants have identified candidates involved in renal calcium handling, such as the transient rec eptor potential vanilloid 5 (TRPV5), which is an important player in Ca2+ homeostasis. TheTRPV5 channel also plays a role in renal calcium transport, and may be the future target of therapies for individuals at risk for nephrolithiasis. [15]

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