The kallikrein-kinin and renin-angiotensin systems in nephrotic syndrome

We previously found that virtually all patients with nephrotic syndrome (NS) excrete supranormal amounts of urinary kallikrein; it is known that activity of the renin-angiotensin system (RAS) is increased in some such patients. We therefore studied the relationship between urinary kallikrein excretion (UKa) and plasma renin activity (PRA) in 16 patients with NS. Compared with healthy controls, PRA was normal in 8 subjects and elevated in 8; UKa was elevated in the high-renin group (40.4 +/- 5.2 nkat/24 h, normals 12.0 +/- 1.1). UKa was also elevated in the normal renin group (25.7 +/- 2.4 nkat/24 h) but to a significantly lesser degree. Significant activity in plasma against a specific substrate of glandular and renal kallikreins was observed in 8 of 10 patients with NS. Such activity was not found in plasma of 17 patients with glomerulonephritis without NS, or in 10 healthy controls. The results are in keeping with previous suggestions of a functional link between the renal kallikrein-kinin system (KKS) and the RAS, but indicate that the renal KKS is activated in NS, in some cases independently of the RAS. It is possible that renal kallikrein reaches the systemic circulation in some patients with NS.