Genetic Predisposition to Formation of Calcium Oxalate Renal Calculi

Background and objectives Kidney stones and their risk factors aggregate in families, yet few studies have systematically estimated heritabilities and genetic correlations of the numerous urinary traits associated with risk of kidney stones.Design, setting, participants, & measurements Twenty-four-hour urine samples were collected from the Genetic Epidemiology Network of Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary determinants of supersaturation. Diet was assessed using the Viocare food frequency questionnaire. Heritabilities and genetic correlations among the urinary traits were estimated using variance components methods.Results Samples were available from 811 individuals (344 men, 467 women; mean age 6669 years). Age, sex, and weight were significantly correlated with the majority of urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had strong evidence for heritability (P,0.01) both before and after adjusting for the identified covariates. Among significantly heritable urinary traits, genetic factors explained 20%-36% of interindividual variation after adjustment for covariates. Urinary calcium excretion was significantly genetically correlated with urinary magnesium and with urinary citrate excretion (P,0.05). Although eGFR influenced many urinary traits, controlling for eGFR did not greatly affect estimated heritabilities.Conclusions Evidence from this cohort suggests a strong heritable component to many urinary nephrolithiasis risk factors. Further study of genetic influences on urinary traits relevant for kidney stone pathogenesis is warranted.Clin J Am Soc Nephrol 9: 943-950, 2014.

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“…affected individuals (19)(20)(21)(22). Two published estimates of the heritability (h 2 ) for stone disease are 63%614% and 46%69% (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…Two published estimates of the heritability (h 2 ) for stone disease are 63%614% and 46%69% (21,22). Indeed, the familial clustering index, one epidemiologic indicator of disease heritability, is greater for nephrolithiasis (2.5-4) than for diabetes mellitus (2.0) or hypertension (2.0) (23).…”

Section: Discussionmentioning

confidence: 99%

Heritability of Urinary Traits That Contribute to Nephrolithiasis

Lieske

Turner

Edeh

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Since 1960s, it is a well known fact that having stone-forming family relatives is a predisposition to have urolithiasis. [36][37][38] In a study conducted by Goldfarb DS et al, 39 stone production was observed higher in monozygous than dizygous twins born in Vietnam. The proportion of kidney stone susceptibility attributable to genetic causes 39 was 56% indicating nephrolithiasis is a complex disease on which genetic and environmental factors have impact.…”

Section: Casr In Collecting Ductsmentioning

confidence: 99%

Calcium-sensing receptor gene polymorphisms in patients with calcium urolithiasis: a systematic review

et al. 2014

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Background: Calcium-sensing receptor gene (CaSR) might be a strong component of the complex genetic background regulating calcium excretion and stone formation in kidney. The polymorphisms in different parts of the gene could be associated with calcium stone formation. Objective: The individual studies indicate a correlation between CaSR gene polymorphisms and urolithiasis but not sufficient to draw a precise result. We aimed to search literature to come to a reliable conclusion through a systematic review. Materials and methods: We have serached individiual studies regarding the issue and high quality reviews. We assessed all the studies to draw a conclusion. Conclusion: The genetic background of the neprolithiasis is an interesting issue deserving to be disscussed on. Regading genes of which, CaSR gene polymorphisms is the leading one, are studied in many individual studies but they are not sufficient to have a precise conclusion. Well-oriented and documented, phenotypically homogenous large cohort studies are needed for further evaluation.

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“…[9][10][11] Hypercalciuria and an excess risk of stone formation is seen in patients with Kidney stone disease: pathophysiology, investigation and medical treatment…”

Section: Hypercalciuriamentioning

confidence: 99%