URINARY PHOSPHATE EXCRETION IN THE PATHOPHYSIOLOGY OF IDIOPATHIC RECURRENT CALCIUM UROLITHIASIS - HORMONAL INTERACTIONS AND LIPID-METABOLISM

Previous work in younger males with recurrent idiopathic calcium uroli thiasis (RCU) demonstrated inappropriately high postprandial phosphatu ria, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU pati ents with a mean age corresponding to the life period with peak format ion of calcium-containing stones, two trials were carried out in 155 m ales of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and ca lcium but low in phosphorus. In trial 1, comprising control subjects ( n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years ), phosphate (Pi) excretion and fractional Pi excretion in postprandia l urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were h yperinsulinemic but still normoglycemic versus controls. In trial 2, c arried out in unclassified (in terms of calciuria) RCU patients (n = 1 19, mean age 40 years) only, the post-load Pi-uria was similar in magn itude to Pi-uria of RCU patients in trial 1; increased postprandial Pi -uria was a phenomenon also of normocalciuria but was slightly more pr onounced in hypercalciuria, while changes in calcium phosphate (brushi te) and calcium oxalate supersaturation of urine were unrelated to cal ciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. W hen urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appea red unrelated to age, but positively associated with postprandial glyc emia as the best predictor, followed by insulinemia, insulin resistanc e, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Pi-uria during fasting but impaired renal Pi conser vation in response to a mixed meal, a situation carrying the risk of P i deficiency over the long term; (2) represent a population developing hyperPi-uria despite suppressed PTH; (3) exhibit insulin resistance b ut are still able to maintain normoglycemia at the expense of hyperins ulinemia. It is suggested that calcium-containing renal stones are rel ated to impaired Pi and glucose translocation across cell membranes, a nd that the role of lipids in this setting deserves further investigat ion.