A family-based study of metabolic phenotypes in calcium urolithiasis

A family-based study of metabolic phenotypes in calcium urolithiasis.BackgroundA family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown.MethodsWe evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship.ResultsEighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 ± 0.33 vs. 0.50 ± 0.22 mmol Ca2+/mmol creatinine, respectively, P < 10­5). This corresponded to absolute values of 7.4 ± 3.9 and 5.1 ± 2.3 mmol Ca2+/day, respectively, for affected and unaffected males, and 5.4 ± 2.6 and 4.2 ± 1.9 mmol Ca2+/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage