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Irbesartan delays progression of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Nephropathy Trial

Lookup NU author(s): Professor Rudy Bilous

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Abstract

Background. The Irbesartan Diabetic Nephropathy Trial (IDNT) demonstrated that irbesartan significantly slowed established Type 2 diabetic nephropathy progression. Estimated glomerular filtration rate (eGFR), now widely used to monitor chronic kidney disease (CKD) progression, was not previously examined in IDNT. This post hoc analysis aimed to confirm IDNT results using eGFR as principal outcome measure. Methods. Mean change in eGFR from baseline (Delta eGFR) was analysed using linear mixed-effects models over time and analysis of covariance at end of study on an intention-to-treat basis. Potential treatment response moderators and/or mediators assessed were CKD stage, blood pressure (BP) and proteinuria. Results. Irbesartan significantly slowed the rate of DeGFR decline from 6 to 21 months (P = 0.0048) and 24 to 48 months (P < 0.0001) versus amlodipine and placebo, despite a faster decline in the first month. The longer patients remained on irbesartan the greater the benefit (model-derived estimates for 6-21 and 24-48 month periods were -0.3354 and -0.1947 mL/min/1.73m(2)/month, respectively). Irbesartan slowed the rate of DeGFR decline irrespective of baseline CKD stage, BP or proteinuria level. Irbesartan produced rapid and sustained proteinuria reductions, which only partially mediated treatment response. Irbesartan increased serum potassium, but levels stabilized from 6 to 48 months. Conclusions. In patients with established Type 2 diabetic nephropathy and CKD Stages 1-5, irbesartan safely and significantly slowed the rate of DeGFR decline (-2.34 mL/min/1.73m(2)/year) compared to amlodipine (-3.76 mL/min/1.73m(2)/year) and placebo (-3.52 mL/min/1.73m(2)/year). This rate of decline was slower with longer duration of irbesartan treatment and only partly explained by observed reductions in BP and proteinuria.

Publication metadata

Author(s): Evans M, Bain SC, Hogan S, Bilous RW, on behalf of the Collaborative Study Group participants

Publication type: Article

Publication status: Published

Journal: Nephrology, Dialysis, Transplantation

Year: 2012

Volume: 27

Issue: 6

Pages: 2255-2263

Print publication date: 01/06/2012

Online publication date: 15/12/2011

ISSN (print): 0931-0509

ISSN (electronic): 1460-2385

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/ndt/gfr696

DOI: 10.1093/ndt/gfr696

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