Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy

• Published in: Nephrology, dialysis, transplantation Vol. 23; no. 10; pp. 3174 - 3183
• Main Authors: Galle, Jan, Schwedhelm, Edzard, Pinnetti, Sabine, Böger, Rainer H., Wanner, Christoph
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiotensin II Type 1 Receptor Blockers - therapeutic use; angiotensin receptor blockers; Arginine - analogs & derivatives; Arginine - blood; Associated diseases and complications; Benzimidazoles - therapeutic use; Benzoates - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; C-Reactive Protein - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - complications; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - physiopathology; diabetic nephropathy; Dinoprost - analogs & derivatives; Dinoprost - urine; Double-Blind Method; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Humans; Hypertension - complications; Hypertension - drug therapy; Hypertension - physiopathology; Intensive care medicine; Male; Medical sciences; Middle Aged; Prospective Studies; proteinuria; Proteinuria - prevention & control; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; telmisartan; Tetrazoles - therapeutic use; Valine - analogs & derivatives; Valine - therapeutic use; Valsartan; valsartan; angiotensin receptor blockers; telmisartan; proteinuria; diabetic nephropathy; Endocrinopathy; Type 2 diabetes; Imidazole derivatives; Tetrazole derivatives; Valsartan; Hemodialysis; Peptide hormone; Cardiovascular disease; Extrarenal dialysis; Octapeptide; Angiotensin II; Valine derivatives; Kidney disease; Human; Hypertension; Urinary system disease; Metabolic diseases; Telmisartan; Nephropathy; Benzimidazole derivatives; Biphenyl derivatives; Aminoacid; Renal failure; Antihypertensive agent; Sartan derivatives; Angiotensin antagonist; Comparative study; Proteinuria
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfn230

Background. Renin–angiotensin system blockade reduces proteinuria and prevents nephropathy progression in patients with type 2 diabetes mellitus (T2D). Experimental evidence demonstrates that angiotensin receptor blockers (ARBs) possess anti-inflammatory potential, which might contribute to reducing proteinuria and providing renoprotection. Methods. We conducted a multicentre, double-blind, prospective, parallel-group non-inferiority study of 885 hypertensive [systolic blood pressure/diastolic blood pressure (SBP/DBP) >130/80 mmHg] patients with T2D, proteinuria (≥900 mg/24 h) and serum creatinine (≤3.0 mg/dl) who were randomized to once-daily telmisartan 80 mg or valsartan 160 mg; additional antihypertensive therapy was permitted. The primary endpoint was the change from baseline in the 24-h proteinuria after 12 months. Secondary endpoints included changes in 24-h albuminuria, estimated glomerular filtration rate (eGFR) and inflammatory parameters asymmetrical dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and urinary 8-iso-prostaglandin F2α (8-iso-PGF2α). Results. Telmisartan and valsartan produced comparable reductions in 24-h urinary protein excretion rates: geometric mean reduction (95% confidence interval) [telmisartan, 33% (27–39%); valsartan, 33% (27–38%)]. No significant differences between treatments were seen in changes from baseline in 24-h urinary albumin excretion rate and eGFR at 12 months. With both treatments, greater renoprotection was seen among patients with better blood pressure control. No significant changes in ADMA or CRP were noted in either group after 12 months, but urinary 8-iso-PGF2α levels decreased by 14% with telmisartan and by 7% with valsartan (P = 0.040). Conclusions. In patients with T2D, hypertension and overt nephropathy, the renoprotection afforded by telmisartan and valsartan appears similar, and the study was unable to show any effect beyond that due to blood pressure control. At doses used to treat hypertension, there is no evidence of inflammatory parameters being modified by ARBs in patients with more advanced kidney disease due to T2D.