Major Hypertension Trials in Chronic Kidney Disease
Major randomized trials evaluating blood-pressure lowering and/or antihypertensive drug selection in chronic kidney disease (CKD) include AASK, MDRD, REIN-2, and SPRINT. [1–4]
African American Study of Kidney Disease and Hypertension (AASK)
AASK randomized African American adults with hypertensive CKD to two mean arterial pressure (MAP) goals and to one of three initial antihypertensive drug classes. [5]
Key randomized components included the following:
- Usual MAP goal 102 to 107 mmHg versus low MAP goal ≤92 mmHg. [5]
- Initial regimens with ramipril, amlodipine, or metoprolol in a factorial design. [5]
Modification of Diet in Renal Disease (MDRD) Study
MDRD included randomized comparisons of diet and strict blood-pressure control intended to slow progression of renal disease in nondiabetic CKD. [6–7]
Major blood-pressure component included the following:
- Low versus usual blood-pressure targets in adults with nondiabetic CKD. [7]
Ramipril Efficacy in Nephropathy-2 (REIN-2)
REIN-2 randomized patients with non-diabetic proteinuric CKD who were receiving background ramipril to more versus less intensive blood-pressure control by adding felodipine. [4]
Major randomized components included the following:
- Intensive versus standard diastolic blood-pressure targets using an added calcium-channel blocker strategy on top of ACE inhibition. [4]
Systolic Blood Pressure Intervention Trial (SPRINT) CKD Cohort
SPRINT randomized adults with hypertension but without diabetes to intensive versus standard systolic blood-pressure targets with predefined renal endpoints. [2,8]
Major randomized components included the following:
- Intensive systolic target <120 mmHg versus standard systolic target <140 mmHg. [2,8]
- Inclusion of a CKD subgroup with assessment of cardiovascular and kidney outcomes under the randomized systolic targets. [2,3]
BP-Target Evidence Synthesis Using CKD Patient-Level Data
A patient-level meta-analysis pooled individual randomized data from AASK, ACCORD, MDRD, and SPRINT to compare intensive versus standard systolic BP targets in CKD. [9]
Key pooled comparisons included the following:
- Intensive systolic target <130 mmHg versus standard target <140 mmHg in CKD patients with hypertension. [9]
Trial Relevance to Current CKD Hypertension Practice
AASK, MDRD, and REIN-2 mainly informed evidence about CKD-specific BP target intensity and ACE-inhibitor–centered strategies in CKD populations. [1,4,6]
SPRINT informed evidence about intensive systolic BP lowering for cardiovascular outcomes and renal outcomes in a broader high-risk hypertensive population that included CKD. [2,8]
Commonly Cited High-Impact CKD Hypertension Trial List
The commonly cited “major” hypertension trials in CKD are as follows:
- AASK. [5]
- MDRD. [6–7]
- REIN-2. [4]
- SPRINT (including its CKD subgroup). [2,8]