A family-based study of metabolic phenotypes in calcium urolithiasis

Background. A family history increases the risk of kidney stone passage ind ependent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. Methods. We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluation s simultaneously, including 24-hour urine collection and oral calcium loadi ng. Phenotypes were compared between affected and unaffected sibs from the same sibship. Results. Eighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) fr om 71 families were analyzed. Daily urine calcium excretion was higher in a ffected compared with unaffected sibs (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca2+/mmol creatinine, respectively, P < 10(-5)). This corresponded to abso lute 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+/d ay, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium we re only significant in the first two tertiles (with onset age of stone pass age < 35 years). The fasting urine Ca2+/creatinine ratio was significantly higher in stone formers compared with control sibs (0.46 +/- 0.27 vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca2+/creatinine ratio (0.5 7 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was marginally significantly higher in stone forming sibs (P = 0.04). Other uri ne phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sod ium, ammonium, and volume, were not associated with stone passage. Conclusion. Increased urine calcium excretion is the only phenotype associa ted with a kidney stone formation in these French-Canadian families.