AJP - Renal Physiology, Vol 248, Issue 4 513-F521, Copyright © 1985 by American Physiological Society
Phosphate loading attenuates renal tubular dysfunction induced by maleic acid in the dog
H. Al-Bander, S. B. Etheredge, T. Paukert, M. H. Humphreys and R. C. Morris Jr
The metabolic pathogenesis of the complex renal tubular dysfunction of type
II renal tubular acidosis and Fanconi's syndrome (RTA II/FS) acutely
induced by maleic acid could depend on the occurrence of a positive
feedback loop in cells of the proximal renal tubule: impaired mitochondrial
oxidation----increased glucose uptake----increased formation and
concentration of phosphorylated glycolytic intermediates----limitation on
availability of cellular inorganic phosphate----more severely impaired
mitochondrial oxidative metabolism. To test this hypothesis we
intravenously administered maleic acid both alone and after initiating
intravenously administered neutral sodium phosphate, sodium sulfate, or
sodium chloride to 10 unanesthetized trained female dogs undergoing water
diuresis. We made the following observations: 1) Administration of maleic
acid alone predictably induced dose-dependent increments in urine flow (V)
and in renal clearance of HCO3-, Na+, K+, and alpha-aminonitrogen and a
pronounced increase in the renal clearance and excretion of citrate. 2)
Prior phosphate loading, which increased the plasma concentration of
phosphate from 2.5 +/- 0.20 to 11.3 +/- 2 mg/dl: a) attenuated the
increment in renal clearance of HCO3- by one-half even though the filtered
load of bicarbonate was higher by 37%, owing to the higher values of both
GFR and plasma bicarbonate concentration that obtained with phosphate
loading; b) prevented the increment in renal clearance and excretion of
alpha-aminonitrogen; c) significantly attenuated the increments in V and
renal clearance of K+; but d) did not affect the increment in renal
clearance and excretion of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)
