RAS blockade in chronic kidney disease may reduce cardiovascular, renal events.

CHICAGO -- Routine use of renin angiotensin system blockers is indicated in patients with chronic kidney disease as part of a strategy to reduce cardiovascular and renal events, Dr. Matthew Weir said at the annual meeting of the American Society of Hypertension.

Patients with chronic kidney disease benefit as much as, if not more than, the general population from the antihypertensive and antiproteinuric effects of renin angiotensin system (RAS) blockade because they are at increased risk for cardiovascular disease.

Decreased glomerular filtration rate (GFR), a specific indication of chronic kidney disease, has consistently been found to be an independent risk factor for cardiovascular disease outcomes and all-cause mortality.

Growing evidence, including a well-designed trial from China (N. Engl. J. Med. 2006;354:131-40), suggests that the sicker the kidney, the greater the risk-reduction benefit with RAS blockade.

But there is anxiety about using ACE inhibitors or angiotensin II receptor blockers (ARBs) in patients with higher serum creatinine levels or reduced GFR because of concern that those levels will rise, said Dr. Weir, professor and director of the nephrology division, University of Maryland, Baltimore.

Because RAS blockers are designed to reduce glomerular capillary pressure, there will be a functional increase in serum creatinine or a decrease in estimated GFR. That increase or decrease can average 15%-30%, depending on volume status, renal artery anatomy, and cotherapies the patient is receiving. The functional change in GFR results in a long-term anatomic advantage, because the reduced capillary pressure results in less injury to the glomerular structure, Dr. Weir said.

In addition, fluctuations in serum creatinine and potassium are predictable, and discontinuation of RAS blockade is almost always avoidable.

If creatinine increases by more than 30%, Dr. Weir suggests evaluating the patient's use of diuretics and volume status, and ruling out concomitant use of NSAIDs. If the first two points are unlikely causes, then clinically significant renal artery stenosis should be ruled out.

If serum potassium increases by more than 0.5 mEq/L, then rule out eating too much fruit or other foods that are high in potassium; rule out concomitant use of NSAIDs, salt substitutes, and potassium-sparing diuretics such as triamterene, spironolactone, and eplerenone; and consider type 4 renal tubular acidosis.

Hyperkalemia has been reported in some ARB trials, but medication was discontinued in only a small percentage of patients. Hyperkalemia is unusual, Dr. Weir said, because the kidney develops homeostatic mechanisms mediated by an increase in sodium potassium adenosinetriphosphatase activity in the renal tubular epithelial cells of the cortical collecting duct. Only type 4 renal tubular acidosis, NSAIDs, or hypoaldosteronism limit this homeostatic effect, he added.

Other clinical pearls included adjusting the dose of RAS blocker based on estimated GFR and known excretory routes; monitoring the patient's weight daily, especially if there is a change in the RAS blocker or diuretic dose; and more frequently assessing serum potassium and creatinine levels with dose changes or diuretic changes, or with gastrointestinal illness.

BY PATRICE WENDLING

Chicago Bureau