Laboratory Investigation

Kidney International (1989) 36, 1003–1010; doi:10.1038/ki.1989.294

Renal kallikrein responses to dietary protein: A possible mediator of hyperfiltration

Ayad A Jaffa1, John N Harvey1, Susan E Sutherland1, Harry S Margolius1 and Ronald K Mayfield1

1Departments of Medicine and Pharmacology, Medical University of South Carolina, and Veterans Administration Medical Center, Charleston, South Carolina, USA

Correspondence: Dr Ronald K Mayfield, Department of Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.

Received 14 March 1988; Revised 12 July 1989; Accepted 18 July 1989.

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Abstract

Renal kallikrein responses to dietary protein: A possible mediator of hyperfiltration. We studied GFR, RPF and renal kallikrein in rats fed 9%, 25%, or 50% protein (casein) diets for 8 to 13 days. GFR and RPF increased progressively with increasing dietary protein. Renal excretion of active kallikrein (microg/day) was 128 plusminus 9, 174 plusminus 11 and 228 plusminus 14 in 9%, 25%, and 50% protein-fed rats, respectively (P < 0.02 or less between groups). Prokallikrein excretion in these groups was 23 plusminus 7, 77 plusminus 11 and 118 plusminus 15 microg/day, respectively (P < 0.005 or less between groups). The in vivo renal kallikrein synthesis rate, relative to total protein synthesis, was reduced in 9% protein-fed rats (2.74 plusminus 0.24) compared to rats fed 25% (3.93 plusminus 0.34, P < 0.02) or 50% protein (4.41 plusminus 0.30, P < 0.001). These changes in synthesis and excretion rates were not accompanied by changes in renal tissue levels of active or prokallikrein. In all groups, GFR and RPF correlated directly with the renal excretion of active kallikrein, prokallikrein or total kallikrein (r = 0.41 to 0.66, P < 0.01). Treatment of 50% protein-fed rats with aprotinin, a kallikrein inhibitor, markedly lowered renal and urinary kallikrein-like esterase activity. Left kidney GFR and RPF were significantly reduced in aprotinin-treated rats compared to vehicle-treated rats (1.54 plusminus 0.15 and 4.86 plusminus 0.38 ml/min vs. 1.89 plusminus 0.10 and 5.93 plusminus 0.22 ml/min, GFR and RPF, respectively, P < 0.05 or less). Protein-induced changes in renal kallikrein synthesis and excretion could not be explained by changes in aldosterone excretion, plasma renin activity, or electrolyte and water intake or excretion. The data suggest that renal kallikrein and kinins participate in mediating the renal vasodilatory effect of dietary protein.

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