BP control strategies that start with RAS inhibitors can prevent progression to overt nephropathy.


NEW ORLEANS—Microalbuminuria is a biomarker for vascular disease and warrants aggressive treatment, which may prevent progression to overt nephropathy and reduce the risk of cardiovascular events, said Debjani Mukherjee, MD, at the 23rd scientific meeting of the American Society of Hypertension.

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The earliest clinical evidence of nephropathy is microalbuminuria. With aggressive BP management starting with inhibitors of the renin-angiotensin system (RAS), microalbuminuria is reversible and progression to overt nephropathy can be prevented.


“The greater the reduction in proteinuria, the greater the renoprotection,” said Dr. Mukherjee, assistant professor in the department of community health and family medicine at the  University of Florida College of Medicine in Gainesville. CKD patients are also in the highest risk group for cardiovascular events, he said.


Microalbuminuria is associated with an approximate doubling of the risk of major cardiovascular events and all-cause mortality, and a tripling of the risk for hospitalization for congestive heart failure. It is at the stage of microalbuminuria when vascular disease is at a potentially treatable stage.


“Reduction in microalbuminuria should be a treatment goal in addition to achieving goal blood pressure,” said Dr. Mukherjee.


In the Losartan Intervention for Endpoint Reduction (LIFE) trial, patients with the greatest reduction in albuminuria had the lowest cardiovascular event rate (J Hypertens. 2004;22:1805-1811), he noted.


Goal BP in patients with renal disease is less than 130/80 mm Hg, and usually requires three or more drugs to achieve, he added.


According to the National Kidney Foundation practice guidelines, the progression to overt nephropathy can be prevented by angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The antiproteinuric effects of ACE inhibitors is greater in patients with higher levels of proteinuria. Diuretics may potentiate the effects of a RAS-blocking agent in nondiabetic kidney disease.


ACE inhibitors should be started in nondiabetic patients with hypertension and nephropathy. A meta-analysis of 11 randomized controlled trials found better BP control, lower urinary protein excretion, and a 30% reduction in the risk of kidney failure in patients randomized to treatment with ACE inhibitors (Ann Intern Med. 2001; 135:73-87).


Clinicians are often concerned about using ACE inhibitors in patients with advanced CKD for fear of increasing serum creatinine and serum potassium levels, noted Dr. Mukherjee. “ACE inhibitors are generally safe in patients with stage 4 CKD,” he said.


Benazepril was found to slow the progression of renal disease by 43% in nondiabetic patients with advanced CKD (N Engl J Med. 2006;354:131-140), and this benefit did not appear to be attributed to BP.


An acceptable rise in serum creatinine of as much as 35% above baseline is acceptable with ACE inhibitors or ARBs, and is not a reason to withhold treatment unless hyperkalemia develops, Dr. Mukherjee said. Avoid the use of nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, and potassium-sparing diuretics if hyperkalemia develops with the use of ACE inhibitors or ARBs.


Add diuretics where applicable and continue the RAS-blocking drug if the potassium is 5 mEq/L or less, he advised. If the glomerular filtration rate (GFR) declines more than 30% from baseline within four weeks of starting therapy, look for other causes, he said.


If proteinuria persists despite ACE inhibitor therapy, dual RAS blockade may be indicated. Renal tissue ACE may not be inhibited by plasma concentrations of ACE inhibitors, he said, and renal angiotensin II is more completely suppressed when ARBs are added to ACE inhibitors. The combination of the two seems to reduce proteinuria more than either drug alone (Ann Intern Med. 2008;148:30-48).


With dual RAS blockade, decreased GFR and hyperkalemia are more frequent in CKD patients, he said.