Activation of transforming growth factor-beta(1) in diabetic kidney disease

Recent data have suggested that certain growth factors and cytokines are in volved in the development of diabetic nephropathy. The aim of this study wa s to investigate whether circulating transforming growth factor beta 1 (TGF -beta(1)) and tumor necrosis factor alpha (TNF-alpha) are associated with d iabetic kidney disease. Serum levels of active and total TGF-beta(1) and TN F-alpha were measured in type 2 diabetic patients with nephropathy (n = 23) or without (n = 35) and normoglycemic controls (n = 12), Serum levels of c irculating active TGF-beta(1) were significantly higher in patients with di abetic nephropathy (0.43 +/- 0.06 ng . mL(-1)) compared with diabetic patie nts without renal involvement (0.23 +/- 0.03 ng mL(-1), P = .002) and healt hy controls (0.24 +/- 0.03 ng mL(-1), P = .001), whereas the levels of tota l (active + latent) TGF-beta(1) were not different between the subgroups. A ctive TGF-beta(1) concentrations were correlated with urinary albumin excre tion (r = .49, P < .003) and serum creatinine (r = .55, P < .01). Sera from patients with type 2 diabetes contained significantly more TNF-alpha than sera from normoglycemic controls (3.07 +/- 0.24 v 1.65 +/- 0.20 pg . mL(-1) , P = .001). However, the comparison of serum TNF-alpha concentrations betw een microalbuminuric and normoalbuminuric diabetic patients showed no signi ficant difference (3.21 +/- 0.28 v 2.97 +/- 0.34 pg . mL(-1), P = .12). In conclusion, type 2 diabetic patients with diabetic nephropathy exhibit incr eased activation of TGF-beta(1) in serum, suggesting an association between circulating TGF-beta(1) activity and the development of renal disease. Cop yright (C) 2000 by W.B. Saunders Company.