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)