REDUCTION OF LEUKOCYTE PROTEOLYTIC-ENZYME ACTIVITY IN DIABETIC-PATIENTS WITH MICROALBUMINURIA AND PROTEINURIA - ITS POSSIBLE ROLE IN DIABETIC NEPHROPATHY

Mesangium enlargement and glomerular basement membrane thickening are cardinal features of diabetic nephropathy. The reasons for these chang es are uncertain but decreased degradation of extracellular matrix may play a role. Mesangium degradation can be modulated by factors intrin sic to the kidney or by factors in the circulation. In this study the capacity of leucocyte proteolytic enzymes to degrade mesangium matrix materials was investigated. Leucocytes were obtained from 57 patients with NIDDM (age 58.3 +/- 8.8 years, duration 9.4 +/- 7.3 years, body m ass index (BMI) 30 +/- 6 kg m(-2), HbA(1c) 7.7 +/- 2.0 %) and 21 contr ol subjects (age 55.1 +/- 14.6 years, BMI 25 +/- 4 kg m(-2)). Leucocyt e lysates from control and NIDDM subjects with normal AER degraded mat rix to the same extent (40.6 +/- 8.2 % vs 42.9 +/- 13.5 %) while lysat es from patients with microalbuminuria and proteinuria were less able to degrade matrix (33.0 +/- 14.2 % and 26.1 +/- 12.7 %, respectively). There was a significant inverse correlation between matrix degradatio n and AER (r = - 0.49) and multiple regression analysis showed that AE R was the most important factor determining degradation rate (R(2) = 0 .24). Degree of metabolic control, age, and blood pressure were not si gnificant factors. The major enzyme(s) responsible for the matrix degr adation was identified as metalloproteinase(s). We conclude that leuco cytes from diabetic patients with abnormal albumin excretion have a de creased proteolytic capacity to degrade extracellular matrix. This may play a role in the glomerular basement membrane thickening and mesang ium expansion which occurs in diabetic nephropathy.