Phosphate loading attenuates renal tubular dysfunction induced by maleic acid in the dog.
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)
D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000596:Amino Acids / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000652:urine; D002712:Chlorides / Q000652:urine; D004285:Dogs; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005919:Glomerular Filtration Rate; D007275:Injections, Intravenous; D008298:Maleates; D009584:Nitrogen / Q000652:urine; D010710:Phosphates / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013431:Sulfates / Q000494:pharmacology
D000596:Amino Acids; D001639:Bicarbonates; D002712:Chlorides; D008298:Maleates; D010710:Phosphates; D013431:Sulfates; C012036:sodium sulfate; C030272:maleic acid; D012964:Sodium; D009584:Nitrogen; D011188:Potassium; C018279:sodium phosphate