Captopril-induced reduction of serum levels of transforming growth factor-beta 1 correlates with long-term renoprotection in insulin-dependent diabetic patients

The renoprotective effect of captopril on progression of diabetic nephropat hy was demonstrated by the Collaborative Study Group Captopril Trial and mi ght be independent of blood pressure, Because angiotensin II is known to st imulate the prosclerotic cytokine, transforming growth factor-beta (TGF-bet a), we postulated that the renoprotective effect may be due to inhibition o f TGF-beta 1 production. TGF-beta 1 levels were measured in serum at baseli ne and 6 months from patients in the captopril trial. TGF-beta 1 analyses w ere performed on all available patient sera. Analysis was performed between the percent change in TGF-beta 1 levels during the first 6 months Versus t he percent change in glomerular filtration rate (GFR) in the subsequent 2 y ears. TGF-beta 1 levels increased by 11% (P = 0.003) in the placebo group ( n = 24), whereas there was a decrease of 14% (P = 0.01) in the captopril gr oup (n = 34). There was an inverse correlation between the percent change i n TGF-beta 1 levels during the first 6 months and the percent change in GFR over the ensuing 2-year period in patients from both the placebo (r = -0.5 5, P = 0.005) and captopril groups (r = -0.45, P = 0.008). In patients with initial GFR below 75 mL/min, there was an even stronger correlation in per cent change in TGF-beta 1 levels and percent change in GFR in both placebo (n = 9, r = -0.69, P = 0.03) and captopril groups (n = 21, r = -0.73, P = 0 .0001), Our data suggest that captopril decreases TGF-beta 1 levels in diab etic nephropathy and that changes in TGF-beta 1 levels may predict the cour se of diabetic nephropathy. (C) 1999 by the National Kidney Foundation, Inc .