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Target Aldosterone Directly to Keep Protein Out of Urine: Presented at ASN

By Roberta Friedman, PhD

SAN DIEGO, CA -- November 17, 2003 -- Eplerenone, a selective blocker of aldosterone's receptor, can avert damage to endothelium and keep the kidneys working properly, according to study findings reported here November 14^th at Renal Week 2003. Low doses of the drug are able to prevent patients with type 2 diabetes from developing proteinuria.

The beneficial effect on renal function was achieved without harmful elevation of serum potassium, study investigator Murray Epstein, MD, said in his presentation. Dr. Epstein is a professor in the department of medicine at the University of Miami, Miami, Florida, United States.

Prior work showed that 200 mg of the drug, recently approved in the U.S. for treating hypertension, prevented type 2 diabetics from developing proteinuria. The new findings are from a study of lower doses.

"If one uses a lower dose, one can achieve the desired effect," Dr. Epstein said, "without paying the piper of hyperkalaemia."

In the multicentre trial of 50 and 100 mg of the drug, the investigators randomised patients who had albuminuria, with a urinary albumen to creatinine ratio (UACR) greater than 50 mg/g. Patients took enalapril 20 mg and added amlodipine 2.5 mg if blood pressure was not controlled adequately by four weeks. Target blood pressure was 130 systolic and 80 diastolic. The dose of amlodipine could be doubled every two weeks to a maximum of 10 mg.

"The need for amlodipine add-on was least in the 100 mg [eplerenone] arm, as we might have expected," Dr. Epstein said.

A total of 270 patients participated. About 70 comprised each treatment group.

At weeks 4, 8, and 12, UACR was lowered by 52% and 55% with the lower and higher doses of eplerenone, respectively. The difference was significant compared to the 13% decrease in UACR in patients who did not take that drug (P < .001).

Thus, kidney function was boosted by the aldosterone blocker, "in both instances exceeding the monotherapy arm," said Dr. Epstein.

Significant incidence of hyperkalaemia did not follow use of the aldosterone blocker, as assessed by either a greater than 5.5 mmol/L elevation on two consecutive occasions, or any elevation above 6.0 mmol/L. However, Dr. Epstein noted, hyperkalaemia occurred numerically more often with eplerenone: High serum potassium was documented in four of 86 patients taking the high dose and in two of 91 taking the low dose, compared to only one of the patients not taking the drug.

Adverse effects, including impotence, gynecomastia or mastodynia, were not associated with the use of eplerenone.

Dr. Epstein agreed with a comment from the audience -- that if one tries to prevent proteinuria by raising the dose of an ACE inhibitor, that would really risk hyperkalaemia.

The study was funded by Pfizer, Inc.


[Study title: The Selective Aldosterone Blocker Eplerenone Reduces Proteinuria Without Concomitant Hyperkalemia. Abstract F-FC026]

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