title: Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Louisville School of Medicine, KY 40292.
authors.forename: J J
authors.initials: JJ
authors.lastname: Miller
authors.forename: D G
authors.initials: DG
authors.lastname: Changaris
authors.forename: R S
authors.initials: RS
authors.lastname: Levy
mesh_terms: 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
chemical_list: D003404:Creatinine; D002268:Carboxypeptidases; C055883:angiotensin-related carboxypeptidase