Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An e nzyme preparation with specific activity of 102 Ug(-1) protein was obtained . The urinary activities of neutral endopeptidase and alanine aminopeptidas e were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14 .1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increase s in the rate of excretion of these enzymes (2.5- and 3.5-fold), respective ly, were observed in patients suffering from acute tubular insufficiency an d even lower increases, 2- and 1.5-fold, respectively, were observed in pat ients with chronic renal diseases. In diabetics and kidney transplant patie nts the enzyme excretion rates were within the reference range. Assay of bo th transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could b e employed as differentiation markers between acute and chronic tubular ins ufficiency. (C) 2000 Elsevier Science B.V. All rights reserved.