INAPPROPRIATE PHOSPHATE EXCRETION IN IDIOPATHIC HYPERCALCIURIA - THE KEY TO A COMMON-CAUSE AND FUTURE TREATMENT

Aims-To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosp hate leak and enhancement of 1.25-(OH)(2)-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further i nvestigation with a view to new management. Methods-An oral calcium lo ading test was administered to 15 patients with renal stones and 10 no rmal controls in the fasting state: urine and blood were collected hou rly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone ( PTH), and phosphate were measured together with urine calcium clearanc e and urinary phosphate from which the TmPO4/glomerular filtration rat e (GFR) ratio was calculated. Serum 1,25-(OH)(2)-vitamin D was measure d in the first serum sample. In addition, 24 hour urine calcium result s were collected retrospectively from the patients' case notes over th e previous 18 months. Results-In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 com pared with 2.10 in controls) and increased calcium clearance. Serum co rrected calcium and PTH concentrations did not differ between the grou ps. After calcium loading, serum calcium and urine calcium clearance r ose in both groups, with patients with renal stones experiencing a gre ater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (g reater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium co ncentration. Patients also had notably greater phosphaturia compared w ith the serum calcium concentration for any given PTH value. Serum 1,2 5-(OH)(2)-vitamin D was higher in patients than controls and for any 1 ,25-(OH)(2)-vitamin D concentration phosphaturia measured against seru m calcium was greater in patients than controls. 1,25-(OH)(2)-vitamin D did not correlate with phosphaturia relative to serum calcium concen trations within the patient and control groups. Conclusions-It is prop osed that patients with idiopathic hypercalciuria have an (inappropria tely high phosphate excretion for any given serum calcium concentratio n. Loss of phosphate may induce increased activation of 1,25-(OH)(2)-v itamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.