Genetic heritability of urinary stone risk in identical twins

Quantitative measurements of urinary parameters are valuable clinical tools for predicting the risk of nephrolithiasis. To our knowledge no previous studies have evaluated the heritability of urinary stone risk in identical twins. Because these individuals share identical genetics, the R defined by their phenotypic data are theoretically equal to the entire population H2.

A total of 12 sets of healthy homozygous twins, including 4 males and 8 females for a total of 24 individuals, with a mean age of 25.9 years (range 21 to 36) volunteered for this study. All subjects provided informed written consent before assessment. Urinary stone risk profiles were done elsewhere on 2 consecutive days after 5 days of a standardized diet (170 mEq Na and 2500 kcal). Linear regression was performed on the data to determine R. Because identical twins were used, R was theoretically an estimate of H2.

Certain urinary stone risk markers were highly heritable, including urinary calcium (94%), oxalate (94%), citrate (95%), uric acid (96%) and brushite supersaturation (90%), as determined by genotype (H2 90% or greater). Uric acid supersaturation (58%) and urinary sodium (64%) had low degrees of heritability.

H2 is a measure of how much of the total variance in phenotype results from differences in genotype, as opposed to environmental differences. For example, an H2 of 95% for citrate suggests that genetic differences account for 95% of the variation in urinary citrate and environmental differences account for the remaining 5%. Therefore urinary calcium, oxalate and citrate are primarily determined by genotype, while environmental factors, particularly those that impact urine pH and urinary volume, may be increasingly important for determining uric acid supersaturation.