AJP - Renal Physiology, Vol 251, Issue 4 642-F646, Copyright © 1986 by American Physiological Society
Prevention of hypercalcemia-induced renal concentrating defect and tissue calcium accumulation
D. C. Harris, P. A. Gabow, S. L. Linas, D. E. Rosendale, S. P. Guggenheim and R. W. Schrier
The mechanism of the concentrating defect of hypercalcemia is explored by
examining the effect of concomitant phosphate restriction. Rats were pair
fed a normal phosphorus diet, without (group 1) or with dihydrotachysterol
(group 2), or a low-phosphorus diet (group 3). Hypercalcemia was comparable
in groups 2 (12.1 +/- 0.6 mg/dl) and 3 (11.8 +/- 0.4 mg/dl), but serum
phosphate was lower in group 3 than group 2 (3.8 +/- 0.7 vs. 7.1 +/- 1.1
mg/dl, P less than 0.005). Group 2 rats had impaired maximum urinary
concentration after 24 h of fluid deprivation (2,441 +/- 450 mosmol/kg H2O,
P less than 0.001) compared with group 1 (3,263 +/- 466 mosmol/kg H2O) or
group 3 (3,332 +/- 515 mosmol/kg H2O) animals. Polydipsia and polyuria were
found in group 2 rats only. Tubular calcium reabsorption was higher in
group 2 (83.1 +/- 33.5 mg/24 h, P less than 0.001) than group 1 (47.0 +/-
26.1 mg/24 h) or group 3 (52.8 +/- 19.3 mg/24 h) animals, and medullary
calcium concentration was higher in group 2 (7.57 +/- 3.08 nmol/mg dry wt,
P less than 0.05) as compared to group 1 (5.04 +/- 1.37 nmol/mg dry wt) or
group 3 (5.32 +/- 0.98 nmol/mg dry wt) rats. Total medullary solute
concentration was significantly higher in group 3 than group 2 animals.
Thus phosphate restriction prevents the defect of urinary concentrating
ability of chronic hypercalcemia, probably by decreasing tubular uptake and
tissue accumulation of calcium.
