Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy

To evaluate the role of circulating and renal endothelin-1 (ET-1) in early diabetic nephropathy, plasma ET-1 levels and urinary ET-1 excretion were evaluated in lean, normotensive patients affected by non–insulin-dependent diabetes (NIDDM) either with (n = 9, NIDDM+) or without microalbuminuria (n = 18, NIDDM−); in never-treated, lean, essential hypertensive patients with (n = 12, EH+) or without microalbuminuria (n = 10, EH−); and in healthy volunteers (n = 12). Results showed higher plasma ET-1 levels in NIDDM+ (1.97 ± 0.58 pg/mL) than in NIDDM− (1.59 ± 0.14 pg/mL, P = .013), EH+ (1.40 ± 0.21 pg/mL, P = .005), EH− (0.91 ± 0.19 pg/mL, P< .0001), and controls (0.60 ± 0.10 pg/mL, P< .0001). The circulating ET-1 concentration was also higher in EH+ than EH− and controls (P< .0001). Urinary ET-1 excretion did not differ (P = .387, NS) between NIDDM+ (48.5 ± 20.1 pg/min) and NIDDM− (40.9 ± 21.6 pg/min), but was significantly reduced (P< .0001) in both groups compared with controls (70.0 ± 15.5 pg/min). Similar findings were observed in hypertensive subgroups. No correlations were found between urinary ET-1 and other variables, including plasma ET-1 levels, in all groups. In conclusion, NIDDM+ is accompanied by a significant increase in plasma ET-1 levels. A significant elevation of circulating ET-1 concentration was evident also in NIDDM−, suggesting that early abnormalities of ET-1 production might precede the microalbuminuric phase of diabetes-related renal damage.