Effects of Losartan on Urinary Secretion of Extracellular Matrix and Their Modulators in Type 2 Diabetes Mellitus Patients with Microalbuminuria

Woo, Vincent; Lian-Song ni; Hak, Dixie; Bernard, Lori; Fuqin Zhu; Khan, Shagufta; Ma, Gouping M.; Penner, Brian; Shen, Garry X.
December 2006
Clinical & Investigative Medicine;Dec2006, Vol. 29 Issue 6, p365
Academic Journal
Purpose: Angiotensin II receptor Type 1 antagonists postpone the development of nephropathy in type 2 diabetes mellitus (DM). We hypothesize that Losartan may ameliorate renal function in diabetic patients through the regulation on the generation of transforming growth factor (TGF)-β and fibrinolytic regulators. Methods: Twenty-two type 2 DM patients with microalbuminuria were treated with 50–100 mg/day of Losartan for 6 months. Urinary secretion of TTGF-, plasminogen activator inhibitor-1 (PAI-1), tissue and urokinase plasminogen activators (tPA and uPA) fibronectin, collagen IV and plasma levels of TGF-β, PAI-1, tPA and uPA of the patients before and after the treatment were analyzed using enzyme-linked immunoabosorbance assay. Results: Losartan effectively reduced arterial blood pressure and urinary albumin excretion. The levels of TGF-β in urine, but no in plasma, were reduced after 2, 4 and 6 months of the treatment (-32% to -48%, P<0.05 or 0.01). Urinary or plasma levels of PAI-1, tPA or uPA, and urinary secretion of fibronectin or collagen IV were not significantly altered Losartan treatment. Urinary levels of collagen IV positively correlated with uPA, and that of fibronectin negatively correlated with PAI-1 in the patients (P<0.01). Urinary TGF-β negatively correlated uPA in urine of the patients (<0.01). Conclusion: Losartan reduced excretion of TGF-β and albumin in type 2 DM patients with microalbuminuria. Fibrinolytic regulators and TGF-β are implicated in the regulation of ECM turnover in kidneys of the patients with diabetic nephropathy.


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