A Twin Study of Genetic Influences on Nephrolithiasis in Women and Men

Abstract

Background Nephrolithiasis is a complex phenotype influenced by both genetic and environmental factors. Previously we found a genetic component to stone disease using a sample of male twin pairs. We now report on the genetic contribution to stones in a sample of female and male twin pairs. Methods We conducted a classic twin study of kidney stones using the Washington State Twin Registry. Data were collected by questionnaire to obtain self-reported history of kidney stones. Univariate structural equation modeling was used to determine the relative contributions of additive genetics, common environment, and unique environment. Results There were 7053 same-sex pairs with kidney stone data. The mean age of the sample was 39 years, similar in women and men. The prevalence of stones was 4.9% of women and 6.2% of men. We found significant contributions from genetics and the unique environment ( P < 0.05 for both) for the risk for stone disease in women and men. There was no significant contribution of the common environment for either sex. After adjusting for age, heritability was 46% (95% confidence interval 0.36–0.56) in women and 57% (0.46–0.68) in men, which was significantly different ( P < 0.05). Conclusions Nephrolithiasis in women has a heritable component less than that we again demonstrate in men. This finding may in part explain why more stone formers are men than women. Women twins demonstrated a greater effect of the unique environment on stone prevalence. The specific environmental risk factors that account for this effect are not currently known.

The Role of Imaging in Diagnosis of Urolithiasis and Nephrolithiasis—A Literature Review Article

“…An SWL typically takes 60 minutes. shion once the stone is located shockwaves from outside the body are targeted at a kidney stone causing the stone to fragment [2]. Stones are broken into fragments that are generally small enough to pass in urine if large pieces remain ureteroscopy or another shockwave procedure can be performed [23].…”

“…Kidney stone or Urinary tract stones have many names including nephrolithiasis/urolithiasis [1] which is actually formation of stones along the nephrolithiasis or urinary tract which is stones forming specifically in the nephron or the kidneys to make things even more confusing; kidney stones or urinary can also be called renal or urinary calculi. Calculi essentially mean stones [2]. However these words are used interchangeably but essentially mean the same thing of kidney stones.…”

Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study

“…The reported etiology of urolithiasis is multifactorial involving environmental and genetic risk factors with heritability of 50% [5]. Only a few Genome Wide Association Studies (GWAS) are available regarding urolithiasis (predominantly from European and Japanese cohorts) that identified common genetic variants in various genetic loci regulating calcium and phosphate metabolism, urinary transporters and macromolecules among others, as urolithiasis associated risk factors [6,7].…”

Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study

“…In kidneys, osteopontin is produced by renal epithelial cells and secreted into the urine as a normal macromolecular constituent of it (13). The hypothesis that osteopontin may play a critical role in modulating renal stone formation is supported by many observations such as; (1) SPP1 as organic component in the matrix of renal stones (14); (2) SPP1 as important regulator of renal calcification (15); (3) Changes in SPP1 expression and urinary SPP1 levels in hyperoxaluric rats and human subjects with urolithiasis, respectively (16); (4) In vitro cell culture based studies and in vivo SPP1 knockout animal models suggesting an important role of osteopontin in various phases of renal stone formation, including crystal nucleation, aggregation, retention, adhesion to renal epithelial cells and stone formation (17,18); and (5) Candidate gene association studies demonstrating association of SPP1 polymorphisms and urolithiasis in different ethnic groups (19,20).…”