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Review
. 2011 Dec 20;8(3):151-62.
doi: 10.1038/nrneph.2011.211.

Genetic determinants of urolithiasis

Carla G Monico  1 , Dawn S Milliner
Affiliations
Review

Genetic determinants of urolithiasis

Carla G Monico et al. Nat Rev Nephrol. .

Abstract

Urolithiasis affects approximately 10% of individuals in Western societies by the seventh decade of life. The most common form, idiopathic calcium oxalate urolithiasis, results from the interaction of multiple genes and their interplay with dietary and environmental factors. To date, considerable progress has been made in identifying the metabolic risk factors that predispose to this complex trait, among which hypercalciuria predominates. The specific genetic and epigenetic factors involved in urolithiasis have remained less clear, partly owing to the candidate gene and linkage methods that have been available until now, being inherently low in their power of resolution and in assessing modest effects in complex traits. However, together with investigations of rare, Mendelian forms of urolithiasis associated with various metabolic risk factors, these methods have afforded insights into biological pathways that seem to underlie the development of stones in the urinary tract. Monogenic diseases account for a greater proportion of stone formers in children and adolescents than in adults. Early diagnosis of monogenic forms of urolithiasis is of importance owing to associated renal injury and other potentially treatable disease manifestations, but diagnosis is often delayed because of a lack of familiarity with these rare disorders. In this Review, we will discuss advances in the understanding of the genetics underlying polygenic and monogenic forms of urolithiasis.

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Figures

Figure 1
Figure 1
Transporter, channel and receptor proteins of the renal tubule implicated in urolithiasis.
Figure 2
Figure 2
Kidney biopsy tissue of a patient with APRT deficiency demonstrating reddish brown crystals of 2,8-dihydroxyadenine.
Figure 3
Figure 3
Photomicrograph of 2,8-DHA crystals in the urine of a patient with APRT deficiency.
Figure 4
Figure 4
Kidney biopsy tissue of a patient with primary hyperoxaluria demonstrating calcium oxalate crystals and associated inflammatory response (arrow)..
Figure 5
Figure 5
Photomicrograph of cystine crystals in the urine.
See this image and copyright information in PMC

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