Phosphate loading attenuates renal tubular dysfunction induced by maleic acid in the dog
Al-Bander, H.; Etheredge, S.B.; Paukert, T.; Humphreys, M.H.; Morris, R.C.
American Journal of Physiology 248(4 Pt 2): F513-F521
1985
ISSN/ISBN: 0002-9513 PMID: 3985158 Document Number: 267215
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 .fwdarw. increased glucose uptake .fwdarw. increased formation and concentration of phosphorylated glycolytic intermediates .fwdarw. limitation on availability of cellular inorganic phosphatge .fwdarw. more severaly impaired mitochondrial oxidative metabolism. To test this hypothesis maleic acid was administered intravenously both alone and after initiating i.v administered neutral sodium phosphate, sodium chloride to 10 unanesthetized trained female dogs undergoing water diuresis. 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. Prior phosphate loading, which increased the plasma concentration of phosphate from 2.5 .+-. 0.20 to 11.3 .+-. 2 mg/gl: 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; prevented the increment in renal clearance and excretion of .alpha.-aminonitrogen; significantly attenuated the increments in V and renal clearance of K+; but did not effect the increment in renal clearance and excretion of citrate. The severity of the RTA II/FS induced by maleic acid was not affected by prior loading with sodium sulfate or sodium chloride. An acetazolamide-induced increase in renal clearance of bicarbonate similar in magnitude to that induced by maleic acid was not affected by prior loading with sodium phosphate. Apparently, the complex renal dysfunction induced by maleic acid in the dog is differentially attenuated by prior phosphate loading and that the phenomenon of attenuation by phosphate loading is one of considerable specificity. The findings provide support forthe hypothesis stated.