Effect of Maleate on Tubular Protein Reabsorption in Dog Kidneys

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Abstract
To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg · kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 ± 3 to 48 ± 6 µmol·min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the ‘trapped-label’ method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg·min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg·kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg·min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-β-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.

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