Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients

Transforming growth factor-beta-1 (TGF-b1) and Endothelin-1 (ET1) have been implicated in the pathogenesis of diabetic renal disease. To evaluate if renal production of TGF-b1 and ET-1 is enhanced in diabetic patients, we studied diabetic (D) and non-diabetic patients (N) with varying degrees of renal function undergoing elective cardiac cathetehzation. A thermodilution catheter was inserted into the left renal vein for blood sampling and measurement of renal blood flow (RBF). Renal vein (RV) and aortic (AO) plasma levels of TGF-b1 and ET-1 levels were measured by sandwich ELISA and RIA, respectively. 22 patients were enrolled, 11 N and 11 D ( all NIDDM, 3 taking insulin). Renal vein (RV) levels of TGF-bt were almost two-fold greater in D vs N (15.6 ±1.9 vs 8.4 ±0.8 ng/ml, respectively, P=0.003) but not different in the aortic (Ao) samples (14.2 ±1.9 vs 13.4 ±1.1 ng/ml). 7/11 of D had greater renal vein levels than aortic levels, indicating renal production of TGF-b1 whereas all 11 of N had lower renal vein levels as compared to aortic levels, indicating renal clearance of TGF-b1. Urinary levels of TGF-b1 were significantly elevated in D vs N (2.59 ±0.94 vs 0.23 ± 0.09 ng/mg créât, P=0.01 ), demonstrating that impaired renal clearance was not the explanation for elevated renal vein levels. Renal vein TGF-b1 levels were inversely correlated with GFR in both D and N. Both aortic and renal vein levels of ET-1 were significantly greater in D than in N, (Ao: 42 ±4.3 vs 29.3 ±1.5, P=0.01; RV: 44.1 ±4.4 vs 28.8 ±1.5 fM, P<0.01). We conclude that patients with NIDDM manifest net renal production of TGF-b1 and have elevated systemic levels of ET-1 which may contribute to the development of diabetic nephropathy.