Background/Aim: Adiponectin, an adipocyte-derived protein, has been shown to exert antidiabetic, anti-inflammatory, and antiatherosclerotic effects. Although recent reports show an increase in the total adiponectin levels in chronic kidney disease patients and in patients with end-stage renal disease, the nature of biodegradation and renal involvement of adiponectin is largely unknown. We aimed at determining whether the high-molecular-weight (HMW) complex of adiponectin is associated with renal insufficiency in type 2 diabetic patients. Methods: A total of 179 type 2 diabetic patients were selected from among outpatients and divided into four groups according to their albumin-to-creatinine ratio: patients with normoalbuminuria (n = 86), patients with microalbuminuria (n = 44), patients with macroalbuminuria (n = 23), and patients on hemodialysis (n = 26). The serum HMW adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. Results: The HMW adiponectin levels were higher in patients on hemodialysis (17.1 +/- 8.2 mu g/ml) and in those with macroalbuminuria (14.3 +/- 8.7 mu g/ml) than in patients with normoalbuminuria (7.2 +/- 5.6 mu g/ml) and microalbuminuria (10.8 +/- 7.0 mu g/ml). Univariate linear regression analysis showed that the HMW adiponectin concentrations correlated negatively with the estimated glomerular filtration rate in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria (r = -0.42, p < 0.001). Multiple stepwise regression analysis disclosed that estimated glomerular filtration rate, pioglitazone therapy, gender differences, and systolic blood pressure were independently associated with HMW adiponectin levels (r = 0.56). Conclusions: The serum HMW adiponectin concentrations are higher in type 2 diabetic patients with nephropathy, and these levels are also associated with renal insufficiency. Copyright (c) 2006 S. Karger AG, Basel