African American Study of Kidney Disease and Hypertension Study (Clinical Trial) (AASK Trial)

General Description

The African American Study of Kidney Disease and Hypertension study (AASK Trial) was a multi-center, randomized clinical trial that investigated the effects of blood pressure (BP) control and the use of specific antihypertensive regimens on the progression of chronic kidney disease (CKD). The study was designed to address the high incidence of CKD in African Americans with hypertension. A two by three factorial study design, including two levels of BP control as defined by mean arterial pressure (MAP) and three different anti-hypertensive regimens, was used. Participants were randomized into two levels of BP control groups, either a goal MAP < 92 mmHg or a goal MAP between 102-107 mmHg inclusive.. The antihypertensive drugs used for treatment were amlodipine, a calcium channel blocker; ramipril, an angiotensin-converting enzyme inhibitor; and metoprolol, a β-blocker. The trial was double-blind (drug administration only). The change in glomerular filtration rate (GFR) as determined by iothalamate clearance was measured as the primary outcome to test the regimens’ efficacy in slowing the rate of decline of kidney function.

The study showed that the angiotensin-converting enzyme inhibitor ramipril was more effective than the beta blocker metoprolol or the dihydropyridine calcium channel blocker amlodipine in slowing the rate of GFR decline. The results suggest that reduction in blood pressure to levels below those currently advocated for cardiovascular risk reduction does not provide readily identifiable benefits to African Americans with hypertensive nephrosclerosis.

Objectives

The AASK study aimed to determine the effects of a lower than usual level of blood pressure control and the use of specific antihypertensive regimens on the progression of renal insufficiency that was clinically attributed to the effects of hypertension on the kidney. Two levels of BP control and 3 different antihypertensive regimens were tested for efficacy in slowing the rate of decline of renal function.

Outcome Measure

The primary outcome measure was change in GFR as determined by iothalamate clearance. Secondary outcome measures included a time-to-event analysis of reduction in GFR by 50% or by 25 ml/min/1.73m2, end-stage renal disease (ESRD), and death to determine the clinical impact of the interventions.

Criteria

The study enrolled African-American men and women between 18 and 70 years of age who presented with hypertension (defined as a sitting diastolic blood pressure of 95 mmHg or more) and reduced renal function (defined as a pre-randomization 125I-iothalamate glomerular filtration rate between 20 65 ml/min/1.73m2).

Exclusion criteria are documented in the study protocol.

Outcome

Results of the AASK study showed that the angiotensin-converting enzyme inhibitor ramipril was was more effective than the beta blocker metoprolol or the dihydropyridine calcium channel blocker amlodipine in slowing the rate of glomerular filtration rate decline in African American patients with mild to moderate renal insufficiency. Notably, there was no significant difference in the rate of decline in kidney function between the 92 mmHg or less and the 102-107 mmHg MAP groups. The study suggests that reduction in blood pressure to levels below those currently advocated for cardiovascular risk reduction does not provide readily identifiable benefits to African Americans with hypertensive nephrosclerosis. While this study provides the basis for the primary use of angiotensin-converting enzyme inhibitors in an African American population, it is undetermined if this represents a class effect for all angiotensin-converting enzyme inhibitors.