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

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 (ΔeGFR) 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 ΔeGFR 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/1.73 m(2)/month, respectively). Irbesartan slowed the rate of ΔeGFR 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 ΔeGFR decline (-2.34 mL/min/1.73 m(2)/year) compared to amlodipine (-3.76 mL/min/1.73 m(2)/year) and placebo (-3.52 mL/min/1.73 m(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.

• Authors: Marc Evans, Stephen C Bain, Simon Hogan, Rudy W Bilous, Collaborative Study Group participants
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 6 Pg. 2255-63 (Jun 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 22172728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Biphenyl Compounds
• Tetrazoles
• Amlodipine
• Creatinine
• Irbesartan

Topics

• Adult
• Aged
• Amlodipine (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Blood Pressure
• Creatinine (blood)
• Diabetes Complications (drug therapy, etiology)
• Diabetes Mellitus, Type 2 (physiopathology)
• Diabetic Nephropathies (drug therapy, etiology)
• Disease Progression
• Female
• Glomerular Filtration Rate
• Humans
• Irbesartan
• Kidney Failure, Chronic (drug therapy, etiology)
• Male
• Middle Aged
• Proteinuria (drug therapy, etiology)
• Tetrazoles (therapeutic use)