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High-Dose Candesartan Reduces Persistent Proteinuria: Presented at ASN

By Bryan DeBusk, PhD

SAN FRANCISCO, CA -- November 6, 2007 -- Patients can achieve a 33% reduction in persistent proteinuria without adverse effects by using eight times the dose of candesartan normally recommended for control of proteinuria.

Ellen D. Burgess, MD, Professor of Medicine, University of Calgary, Calgary, Alberta, Canada, reported the findings here at Renal Week 2007, the American Society of Nephrology (ASN) Annual Meeting.

"Proteinuria has been identified as an independent risk factor for progression of both diabetic and nondiabetic renal disease. The primary objective of our study was to evaluate the effect of high-dose candesartan at 64 and 128 mg per day compared with 16 mg as the recommended dose in Canada as the active control of proteinuria," Dr. Burgess said.

In this double-blind, randomised, controlled trial, 346 patients who had proteinuria (>1 g/24 h) for 6 months discontinued all angiotensin-converting enzyme (ACE) inhibitors and adrenergic receptor blockers and received 16 mg of candesartan for a period of 8 weeks. Two hundred sixty-nine patients who persisted with proteinuria at this dose (mean of 2.66 g/24 h) were randomised to one of three groups: 16, 64, or 128 mg candesartan for 30 weeks.

The three groups were well matched with the overall pool having a mean age of 55.3 years and being 79.6% male. Mean blood pressure at the outset was 132.5/77.5 mm Hg, and participants represented a range of underlying diseases including diabetic nephropathy (53.9%), primary glomerular disease (33.5%), and hypertensive nephrosclerosis (12.6%). Eighty-five percent of participants were receiving diuretics.

Compared with the overall group receiving 16 mg of candesartan (including the 77 patients who did not have persistent proteinuria after 8 weeks), the group receiving 128 mg experienced a 33.05% reduction in proteinuria after 30 weeks (95% confidence interval [CI], -47.5 to -17.44; P <.0001). Compared with the group of patients on 16 mg candesartan whose proteinuria persisted, the group receiving 128 mg experienced a reduction of 44.34% (95% CI, -58 to 26.25; P <.0001).

Average blood pressure in all three groups remained similar throughout, suggesting that decreases in blood pressure do not account for the reduction in proteinuria observed at high doses.

Explaining that the dose can be pushed higher to achieve even greater results, Marc Weinberg, MD, Clinical Professor of Medicine, Boston University, Boston, Massachusetts, United States, said, "We know that we clearly haven't overwhelmed this metabolic pathway... This is the new frontier."


[Presentation Title: Double-Blind Randomized Controlled Trial of High Dose Candesartan Cilexetil in Proteinuric Renal Disease -- Results From SMART (Supra Maximal Atacand Renal Trial. Abstract SA-FC104]

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