NEW YORK (Reuters Health) – In non-diabetic patients with hypertensive kidney disease, the risk of hyperkalemia with angiotensin converting enzyme (ACE) inhibitors is “small,” according to research reported September 28 in the Archives of Internal Medicine.

“There is significant clinical under-utilization of ACE inhibitors and diuretics in the very population that evidence shows (is) the most helped by these agents — i.e., patients with chronic kidney disease,” Dr. Robert A. Phillips said in an email to Reuters Health.

“ACE inhibitors retard progression of chronic kidney disease,” he continued, “but healthcare providers often do not use or prematurely stop ACE inhibitors and diuretics in chronic kidney disease because of clinically insignificant increases in serum creatinine and perceived risk of hyperkalemia.”

Dr. Phillips, of the University of Massachusetts in Worcester, and colleagues determined factors associated with hyperkalemia in 1,094 non-diabetic kidney disease patients treated with an ACE inhibitor (ramipril), a beta-blocker (metoprolol), or a calcium channel blocker (amlodipine).

“We found that the incidence of hyperkalemia was remarkably low,” Dr. Phillips said. The article notes that 80 hyperkalemic events were recorded in 51 subjects, out of a total of 6,497 potassium measurements obtained over 3.0 to 6.4 years.

Compared with a glomerular filtration rate (GFR) higher than 50 mL/min/1.73 m2, hazard ratios for hyperkalemia with a GFR between 31 and 40 and a GFR lower than 30 were 3.61 and 6.81, respectively.

“If baseline or follow-up GFR is greater than 40 (moderately reduced renal function), the risk of hyperkalemia is almost negligible,” Dr. Phillips said.

As expected, ACE inhibitor therapy was associated with significantly more hyperkalemic episodes compared with the calcium channel blocker therapy (hazard ratio, 7.0) and beta blocker therapy (hazard ratio, 2.8).

However, Dr. Phillips told Reuters Health, “using a diuretic reduced the risk of hyperkalemia by nearly 60%.”

These findings have several clinical implications, he said. “First, it is very safe to use ACE inhibitors and diuretics” in non-diabetic patients with chronic kidney disease, “and fears regarding hyperkalemia and significant increases in creatinine are unfounded.”

“Second,” he added, “since we did not detect a hyperkalemic event until after five months of initiation of ACE inhibitors, we feel it is safe to wait at least a month after initiation of therapy before testing for potential increase in potassium.”

“We hope that these findings will encourage physicians and other healthcare providers to be bolder in utilization of ACE inhibitor therapy in chronic kidney disease, since it is a very effective drug class for blunting progression” of disease, Dr. Phillips concluded.

Reference:
Arch Intern Med 2009;169:1587-1594.