Renal tubular effects of chronic phosphate depletion.

Abstract

A B S T R A C T The effects ofchronic phosphate depletion on renal tubular function were evaluated by micropuncture and free water clearance studies in the dog. Proximal tubular punctures demonstrated that chronic hypophosphatemia led to a reduction in ratio of tubular fluid to plasma inulin in late superficial tubules from 1.59+0.08 in control animals to 1.29±0.06 in phosphate-depleted dogs, with proportional inhibitior, of calcium and sodium reabsorption. The chronic decrease in proximal tubular fluid reabsorption was confirmed by the analysis of sustained water diuresis in conscious, phosphate-depleted dogs, before and after repletion of body P04 stores, and in control animals. Urine flow rate/100 ml glomerular filtration rate (V/GFR) was significantly higher in P04 depletion than control (15.8±1.1 vs. 10.7±0.82). In addition, acetazolamide infusion did not increase V/GFR in phosphate-depleted dogs (15.8±1.1 vs. 17.16±0.9), supporting the conclusion that inhibition of proximal tubular fluid reabsorption was responsible for the elevated urine flow rate. P04 repletion over 5 days reduced V/GFR to 9.2±0.7 despite no change in urine osmolality and no change in GFR, further suggesting a specific reversible alteration in proximal tubular reabsorption in phosphate depletion.Although hypercalciuria was a constant finding in phosphate depletion (fractional excretion of calcium of 2.04±0.4% vs. 0.47±0.13% in controls), the enhanced distal delivery of calcium was not a crucial factor; acute phosphate infusion reduced urinary calcium excretion to control values without affecting the reduced proximal tubular reabsorption in either intact or thyroparathyroidectomized phosphate-depleted dogs. The change in distal nephron calcium reabsorp-

Effect of Phosphate Depletion on Magnesium Homeostasis in Rats

“…A decrease in the net tubular reabsorption of magnesium during PD is not surprising because others have reported tubular reabsorptive defects of other substances such as calcium (10), bicarbonate (28), glucose (29), and sodium (30).…”

Renal Tubular Sites of Altered Calcium Transport in Phosphate-depleted Rats

“…Tubular fluid calcium and Na were determined by electron probe microanalysis as previously described (4,5). Urine and plasma calcium, P04, and Na were determined by methods previously described (6).…”

“…Anesthesia and surgery were performed as previously described (5,6). [Methoxy-3H]inulin was infused via the external jugular vein in 0.9% sodium chloride that contained 3.05 meq/ liter CaCl2 at a rate of2.5 ml/100 g weight per h. Tubular localization was aided by intratubular injection of lissamine green (0.1%) via sharpened pipettes (OD c 4 ,um).…”

“…Carotid artery blood pressure was monitored, and only those animals with a mean blood pressure over 100 mm Hg were included in the data reported here. After 150 min ofequilibration, [3][4][5] proximal and 2-10 distal tubules were punctured over the next 90-100 min. An oil block equal to 3-5 tubular diameters was injected distal to the flow of tubular fluid.…”

“…It is of note that whereas reduced proximal TF reabsorption has not been demonstrated in animals placed on low-PO4 diets for brief periods (7), it is regularly seen in more severe PD in both clearance and micropuncture studies (5,8,9 …”