Research Updates in Kidney and Urologic Health

NIDDK Identifies Risks, Measures Burden of Kidney and Urologic Diseases

ACE Inhibitor Protects Kidneys; Ultra-Low BP Provides No Added Benefit

The largest clinical trial ever conducted in African Americans with kidney disease has concluded that an antihypertensive drug from the angiotensin-converting enzyme (ACE) inhibitor drug class is superior to two drugs from two other classes for slowing kidney disease due to hypertension. The study also found that a very low blood pressure provides no additional benefit for the kidneys over the usual target blood pressure. Results appear in the November 20, 2002, issue of the Journal of the American Medical Association.

"We were surprised that the lower blood pressure level didn't have more of an effect on the kidney," said co-author Dr. Lawrence Agodoa, who specializes in kidney diseases at the National Institutes of Health. "But the good news is that we have a new tool—the ACE inhibitor—to improve the health of a large number of African Americans and others who have this type of kidney disease."

Study Design

The African American Study of Kidney Disease and Hypertension (AASK) treated 1,094 patients aged 18 to 70 years who had mild kidney disease of hypertension. Investigators compared a usual, or standard, blood pressure goal of 140/90 mm Hg in 554 patients against a lower goal of 125/75 mm Hg in 540 patients. They also compared drugs from three classes of antihypertensives: the ACE inhibitor ramipril (Altace), the dihydropyridine calcium channel blocker (CCB) amlodipine (Norvasc), and the beta blocker metoprolol (Toprol XL). Patients across 21 centers were followed for 3 to 6.4 years. The study ended September 2001.

Study Results

The ACE inhibitor reduced the risk of reaching the clinical end-points—kidney failure, death, or a 50-percent drop in kidney function—by 22 percent compared with the beta blocker, and by 38 percent compared with the CCB. Primary treatment with the CCB was stopped in September 2000 after data comparisons showed that the ACE inhibitor slowed kidney disease 36 percent more effectively than the CCB and provided 48 percent greater reduction in the risk of kidney failure and death in patients who had at least a gram of protein in the urine. Whereas 155 patients taking the beta blocker reached an end-point, only 126 taking the ACE inhibitor did. In the two blood pressure groups, roughly equal numbers reached an end-point: 167 in the usual-goal group and 173 in the low-goal group.

"The results of this trial will significantly improve the health of thousands of African Americans who suffer from kidney disease due to hypertension" said Dr. John Ruffin, director of the National Center on Minority Health and Health Disparities, which co-funded AASK. "The study also demonstrates the benefit of focusing research on populations most affected."

In the final analysis, even patients with low levels of urine protein benefited greatly from the ACE inhibitor and to a lesser degree from the beta blocker. Both drugs reduce protein in the urine, rising levels of which indicate worsening kidney disease, cause more damage, and predict death from heart disease and stroke. Within 6 months of starting AASK, patients on the CCB had a 58 percent increase in urine protein. In contrast, patients on the beta blocker had a 15 percent decrease and those taking the ACE inhibitor had a 20 percent decrease. The ACE inhibitor reduced the risk of developing high levels of urine protein (greater than 300 mg a day) by 55 percent, and the beta blocker reduced the risk by 35 percent.

Neither reaching the low blood pressure goal nor any of the drugs stopped the decline in glomerular filtration rate (GFR), which drops as kidney disease progresses. However, GFR dropped more rapidly in patients who had higher levels of urine protein, regardless of treatment group. GFR declined by 1.35 mL/min per 1.73 m² in patients who started AASK with low levels of urine protein (300 mg a day or less) compared with a decline of 4.09 mL/min per 1.73 m² in patients with higher urine protein (greater than 300 mg a day).

AASK also showed that while high blood pressure may be more severe and therefore more difficult to control in African Americans, it can be improved. Only 20 percent of patients entered the study with blood pressure levels below the usual goal of 140/90 mm Hg. Within 14 months, nearly 79 percent of people in the low-goal group and nearly 42 percent in the usual-goal group had lowered their blood pressure to 140/90 mm Hg.

New Recommendations

Drugs compared in the study remain important for treating high blood pressure and helping reduce the risk of stroke and kidney and heart disease. The Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure now recommends that people with kidney disease, hypertension, and protein in the urine achieve and maintain blood pressure at or below 130/85 mm Hg.

"People who have kidney disease of hypertension and any protein in the urine should be given the benefit of an ACE inhibitor, unless the drug is contraindicated, along with a diuretic," said Agodoa, who sits on the JNC and heads the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Office of Minority Health Research Coordination. "And anyone who also has heart disease or diabetes, as so many do, should try to reach the JNC goal of 130/85 mm Hg."

Kidney failure is a major expense in the United States, costing patients, insurers, and the Federal Government nearly $20 billion in 2000. Hypertension is a leading cause, accounting for close to 25 percent (87,000) of the nearly 379,000 people treated for kidney failure in 2000. African Americans are six times more likely than whites to develop kidney failure from hypertension and account for 32 percent (122,000) of all treated patients.

AASK was funded by the NIDDK, the National Center on Minority Health and Health Disparities, and the National Center for Research Resources of the National Institutes of Health. Study drugs were provided by Pfizer Inc., AstraZeneca Pharmaceuticals, and King Pharmaceuticals Inc.

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