Impaired renal hemodynamic response to protein feeding in dogs with experimental Fanconi syndrome

These studies were designed to test the hypothesis that intact proximal tubular function is required for protein-stimulated renal vasodilation. In normal chronically instrumented conscious dogs, a meal of raw beef (10 g/kg) caused glomerular filtration rate (GFR) to increase significantly from 63 +/- 5 to 94 +/- 10 ml/min after 90 min, while plasma alpha-amino nitrogen rose from 3.9 +/- 0.2 to 6.7 +/- 0.6 mg/dl. In another group of dogs experimental Fanconi syndrome (generalized proximal tubular dysfunction) was induced with maleic acid (25 mg/kg iv, pH 7.3). GFR fell slightly but significantly from 91 +/- 18 to 66 +/- 9 ml/min after maleic acid, while Na+ excretion rose from 24 +/- 8 to 176 +/- 24 mu eq/min, alpha-amino nitrogen excretion rose from 82 +/- 40 to 148 +/- 47 micrograms/min, and glucose excretion rose from 0.2 +/- 0.1 to 6.1 +/- 1.0 mg/min. In response to a subsequent meat meal, plasma alpha-amino nitrogen rose significantly from 3.8 +/- 0.4 to 6.2 +/- 0.5 mg/dl, but GFR did not change, averaging 66 +/- 9 ml/min over the next 120 min. These results suggest that normal proximal tubular function is necessary for protein-stimulated renal vasodilation to occur. This finding is consistent with the hypothesis that the tubuloglomerular feedback mechanism may be involved in mediating the normal renal hemodynamic response to protein feeding.