AJP - Renal Physiology, Vol 255, Issue 6 1078-F1084, Copyright © 1988 by American Physiological Society
Renal phosphate transport in humoral hypercalcemia of malignancy
L. Sartori, K. L. Insogna and P. Q. Barrett
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Fisher rats bearing the H-500 Leydig cell tumor (LCT) develop humoral
hypercalcemia of malignancy (HHM), which is accompanied by hypophosphatemia
and hyperphosphaturia. To better define the mechanisms underlying the
changes in phosphate metabolism, the activity of sodium-dependent phosphate
uptake (Na+-Pi) in microvillus membrane vesicles (MMV) isolated from the
renal cortex of LCT-bearing rats was studied. Ten days after tumor
transplantation the animals became hypercalcemic, hypophosphatemic, and
hyperphosphaturic, and LCT-MMV showed a specific decrease in Na+-Pi. A
kinetic analysis revealed evidence for both a high- and a low-affinity
system of Na+-Pi. The Vmax of both the low-affinity system and the
high-affinity system were significantly reduced in LCT-MMV. These changes
in Na+-Pi transport were similar to those induced by parathyroid hormone.
In day-10 tumor-bearing animals, daily injections of dichloromethylene
diphosphonate (2.5 mg.kg-1.day-1) prevented the onset of hypercalcemia but
not the reduction in Na+-Pi in LCT-MMV. Our data suggest that in this
animal model of HHM there is a specific and persistent impairment of Na+-Pi
uptake at the level of the renal cortical brush-border membrane, which
contributes to the derangement in phosphate metabolism.
