Outpatient renal stone formers belonging to the established urolithiasis subgroups and controls were examined with respect to urinary and serum citrate (Cit) and several associated variables. Only in the normocalciuric majority of calcium and in uric acid stone formers was Cit in 24-hour urine decreased, but was normal in 2-hour fasting morning, and in 3-hour postprandial urine following a Cit-free test meal. Serum Cit was elevated in normocalciuria, renal and resorptive hypercalciuria. This Cit constellation was associated with either normal (absorptive, renal hypercalciuria) or low (normocalciuria, uric acid stone formers) parathyroid gland function as assessed by serum parathyroid hormone and nephrogenous urinary cyclic AMP, except in patients with primary hyperparathyroidism. In 2-hour morning urine the magnesium/creatinine ratio (normocalciuria) and ammonia excretion (uric acid stone formers) were decreased, while ammonia in 24-hour urine was low in all stone formers. It is suggested that Cit metabolism is altered in renal stone disease in general, and that in normocalciuria, stone inhibitors (Cit; magnesium) may be deficient.

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Summary: The total and Ultrafiltrable citrate of serum were measured in healthy controls, and in patients with calcium-containing kidney stones classified into the various calciuria types (normocalciuria, renal, absorptive, resorptive hypercalciuria). The total citrate in two subgroups (normocalciuria, renal hypercalciuria) was significantly higher than in controls. Two independent analyses showed a mean Ultrafiltrable fraction of 0.86 (controls and stone formers, with the exception of resorptive hypercalciuria) and 0.95 (resorptive hypercalciuria), i.e. the calculated extent of binding of citrate to serum macromolecules (> 10000 Daltons). The differences in the fraction of free citrate between controls and renal stone formers are not sigriificant. The apparent mean association constants are (1/mol) 0.24 X l O 2 (controls) and 0.29 X l O 2 (noimocalciuria). There is a high correlation between the ultrafiltrable fraction and total citrate in the serum, and also between the ratlos urinary/serum creatinine and urinary/ serum total citrate, during a 2 h endogenous creatinine clearance in the morning (fast in g). These findings suggest that 1) there is citrate binding in the serum, 2) the normal portion of free citrate in total serum citrate of normocalciuric stone formers cannot explain the decreased citrate excretion in 24 h urine of these subjects,3) under defined conditions of examination (morning;fasting) urinary citrate is determined largely by the filtered load of citrate in the proximal renal tubüle.

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