Urinary kallikrein excretion in chronic renal failure: relationship to blood pressure and the acute effect of captopril.
Previous studies of the renal kallikrein-kinin system in chronic renal failure (CRF) have given conflicting results. We have assessed activity of this vasoactive hormone system in CRF and investigated a possible relationship to hypertension in patients with CRF: 24-hour urinary kallikrein excretion (UKa) was measured in 22 patients with CRF (9 normotensive and 13 hypertensive) and 11 healthy controls. Age, sex, urine volume, and urinary sodium excretion were similar in each group. Compared with controls, UKa was reduced in both normotensive and hypertensive patients with CRF, with no difference between CRF groups. The reduction in UKa in CRF was less than the reduction in glomerular filtration rate (GFR), as assessed by endogenous creatinine clearance (CCr). When UKa was divided by CCr, UKa/mL CCr was therefore increased, to a similar extent, in both normotensive and hypertensive patients with CRF. This suggests that release of renal kallikrein from functioning nephrons is increased in CRF. The results do not support a role for deficient kallikrein release in the genesis of hypertension in CRF, as previously suggested; however, these abnormalities could be relevant to other aspects of renal function in CRF. The converting-enzyme inhibitor, captopril, was given to 5 patients with CRF, hypertension, and low UKa. Introduction of captopril was followed by a further reduction in UKa in all subjects. Captopril is known to inhibit kininase II, the principal enzyme involved in degradation of kinins; this potentiating effect may be counteracted by a reduction in renal kallikrein release and hence in kinin generation.
Cumming
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AD
Medical Renal Unit, Royal Infirmary, Edinburgh, Scotland.
Lambie
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AT
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000652:urine*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000652:urine
D002216:Captopril; D012964:Sodium; D007610:Kallikreins