Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage.
Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.
Miller
J J
JJ
Department of Biochemistry, University of Louisville School of Medicine, KY 40292.
Changaris
D G
DG
Levy
R S
RS
D002268:Carboxypeptidases / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000652:urine; D006801:Humans; D006977:Hypertension, Renal / Q000201:enzymology / Q000652:urine; D007674:Kidney Diseases / Q000201:enzymology* / Q000652:urine; D008297:Male; D012016:Reference Values
D003404:Creatinine; D002268:Carboxypeptidases; C055883:angiotensin-related carboxypeptidase