Evidence for a Renal PO4 Leak in Patients with Calcium Nephrolithiasis
Patients having recurrent calcium oxalate and/or apatite nephrolithiasis demonstrate hypophosphatemia but normal rates of glomerular filtration and urinary phosphate excretion in comparison to healthy adults without a personal or family history of renal stones. These observations suggest that stone formers have a defect in net renal tubular reabsorption of filtered PO4. We compared the responses of stone formers and of normal subjects to dietary PO4 deprivation in order to assess whether the lower serum PO4 levels in stone formers are the result of a renal PO4 leak or a resetting of the level at which the kidneys regulate serum PO4 levels. Nine male stone formers and 13 healthy male adults were studied while eating normal diets and then while eating a liquid diet providing only 2 mmol PO4/day for 3 days. (Females were not studied because serum PO4 falls in healthy women deprived of dietary PO4.) During control, serum PO4 averaged 1.30 ± 0.06 SE mmol/L in normals and 1.28 ± 0.06 mmol/L in stone formers, values that are not different for these small groups. Control UPO4V averaged 32.4 ± 1.8 mmol/day in normals and 27.9 ± 2.3 mmol/day in the stone formers. These means are also not significantly different. However, after 3 days of dietary phosphate deprivation, mean serum PO4 concentrations declined by −0.18 ± 0.04 mmol/L in stone formers (p < 0.01) but did not change from control in the normal men (+0.05 ± 0.05 mmol/L; NS). The mean change from control in serum PO4 concentrations in stone formers was also significantly different from the change in normals (p < 0.01). In addition, UPO4V on the 3rd day of dietary PO4 deprivation fell to only 4.5 ± 1.0 mmol/day in stone formers, a value significantly higher than that observed in the normal men of 1.8 ± 0.5 mmol/day (p < 0.02). The observations that stone formers fail to achieve normal maximum renal PO4 conservation and demonstrate a fall in serum PO4 concentration in response to dietary PO4 deprivation provides further support for the view that these patients have a renal PO4 leak. The mechanism of such a leak remains to be determined. The suppression of PTH secretion that accompanies dietary PO4 deprivation in normal subjects could be impaired or delayed among stone formers. Alternatively, stone formers may have a defect in a PTH-independent renal tubular PO4 transport process.