Abnormal red-cell calcium pump in patients with idiopathic hypercalciuria

Idiopathic hypercalciuria is a common disorder whose inheritance suggests an enzyme abnormality in calcium transport. We measured calcium-magnesium-ATPase activity in erythrocytes from 38 patients (mean age [± SEM], 40 ± 2.1 years) with idiopathic hypercalciuria (24-hour urinary calcium excretion ≥0.1 per kilogram of body weight) and a history of multiple calcium oxalate kidney stones. As compared with 41 healthy controls, the patients with hypercalciuria had increased erythrocyte-membrane calcium-magnesium-ATPase activity (64.2 ± 2.19 vs. 51.6 ± 1.91 nmol of ATP split per milligram per minute; P <0.01) and increased sodium-potassium pump acitivity (6866 ± 233 vs. 6096 ± 228 μmol of sodium per liter of red cells per hour; P <0.05). No significant difference between the two groups was found in erythrocyte sodium-potassium cotransport, sodium-lithium countertransport, or potassium content. In 66 patients with kidney stones (38 with hypercalciuria and 28 with normal calcium excretion), 24-hour urinary calcium excretion correlated with calcium-magnesium-ATPase activity (r = 0.46, P <0.001). Erythrocyte calcium-magnesium-ATPase activity remained unchanged in eight subjects studied after four months on a low-calcium diet. A study of 30 healthy families found significant correlations between mean values in parents and those in offspring for calcium-magnesium-ATPase (r = 0.68, P <0.001) and urinary calcium excretion (r = 0.45, P <0.02), with no significant correlations between parents with respect to these measures (r = 0.27 and r = 0.08, respectively). We conclude that abnormalities in erythrocyte calcium-magnesium-ATPase activity may represent an inherited defect in calcium transport related to the cause of idopathic hypercalciuria.