Protein-induced glomerular hyperfiltration: Role of hormonal factors

Abstract

High protein diets acutely elevate the glomerular filtration rate. To characterize this response we administered 1 g of protein/kg body weight as a beef steak meal to nine, healthy male subjects and measured glomerular filtration rate (inulin clearance), renal plasma flow (p-amino hippurate clearance), plasma renin activity, aldosterone and plasma and urinary catecholamines. The subjects ingested the meal on three separate days and were pretreated with either placebo, 50 mg indomethacin (to inhibit renal prostaglandin synthesis), or 10 mg enalapril (to inhibit angiotensin II synthesis). Following placebo treatment protein feeding significantly increased the glomerular filtration rate, from a pre-meal level of 101 ± 7 ml/min/l.73 m2 to a post-meal level of 130 ± 6 ml/min/l.73 m2, P<0.005. A parallel rise in renal plasma flow and a fall in renal vascular resistance were noted. Indomethacin pretreatment attenuated the increase in glomerular filtration rate following the protein meal, 105 ± 6 ml/min/l.73 m 1/2 pre-meal level to 118 ± 4 ml/min/l.73 m2 post-meal, P>0.1. Enalapril pretreatment had no significant effect on protein-induced glomerular hyperfiltration. Protein feeding following placebo increased plasma aldosterone concentration while the concentrations were unchanged in the studies where enalapril or indomethacin was administered. Protein feeding following placebo or indomethacin did not alter plasma renin activity while plasma renin activity rose following enalapril administration. Urinary norepinephrine excretion rose while plasma norepinephrine concentration was unchanged in all three study groups. A decrease in urinary dopamine excretion was also noted four hours after the protein meal was ingested. The urinary PGE2 excretion was unchanged following protein loading in the studies when placebo was administered, while it fell by 50% in the studies when indomethacin was administered. Plasma atrial natriuretic peptide concentrations were measured in six additional subjects following a protein meal and the levels remained unchanged. Our data indicate that protein-induced elevation of glomerular filtration rate may be mediated by prostaglandins.