Mineralocorticoid Receptor Antagonists for Hypertension Management in Advanced Chronic Kidney Disease: BLOCK-CKD Trial.

Spironolactone, a steroidal mineralocorticoid receptor antagonist, is recommended as add-on therapy for treatment-resistant/uncontrolled hypertension. However, caution is advised in patients with advanced chronic kidney disease (CKD) due to an increased risk for hyperkalemia. KBP-5074 is a nonsteroidal mineralocorticoid receptor antagonist under investigation for the treatment of treatment-resistant and uncontrolled hypertension in patients with moderate-to-severe CKD. BLOCK-CKD is a phase 2, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of KBP-5074, on top of current therapy, in patients with stage 3B/4 CKD (estimated glomerular filtration rate ≥15 and ≤44 mL/[min·1.73 m2]) and resistant hypertension (trough cuff seated systolic blood pressure ≥140 mm Hg, despite treatment with maximally tolerated doses of 2 or more antihypertensive medicines with complementary mechanisms). Patients (n=240) will be randomized 1:1:1 to once-daily treatment with KBP-5074 0.25 mg, KBP-5074 0.5 mg, or placebo, stratified by estimated glomerular filtration rate (≥30 versus <30 mL/[min·1.73 m2]) and systolic blood pressure (≥160 versus <160 mm Hg). Approximately 30% of enrolled patients should have an estimated glomerular filtration rate of 15 to 29 mL/(min·1.73 m2). The primary efficacy analysis is the change in trough cuff seated systolic blood pressure from baseline to day 84 for the KBP-5074 doses compared with placebo. Changes in urinary albumin-creatinine ratio will be assessed along with changes in serum potassium/incidence of hyperkalemia and changes in estimated glomerular filtration rate and serum creatinine. BLOCK-CKD will determine whether the addition of KBP-5074 will effectively lower blood pressure without an increased risk of hyperkalemia in patients who are not candidates for steroidal mineralocorticoid receptor antagonists due to advanced CKD. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT03574363.

Effects of nitrendipine and cilazapril on renal hemodynamics and albuminuria in hypertensive patients with chronic renal failure.

In 11 hypertensive patients with chronic renal failure we studied the short-term effects of the calcium antagonist nitrendipine, the angiotensin-converting enzyme inhibitor cilazapril, and the combination of both drugs on blood pressure, renal hemodynamics, and proteinuria in a randomized, double-blind, placebo-controlled way. After one week of treatment, blood pressure at 2-5 h after drug administration amounted to 159 +/- 5/101 +/- 3 mm Hg (means +/- SEM) during placebo. Nitrendipine, cilazapril, and the combination lowered mean arterial pressure by 1.4 +/- 1.6 (NS), 6.0 +/- 1.7 (p less than 0.10), and 10.3 +/- 2.1% (p less than 0.01), respectively. Glomerular filtration rate did not change. As compared to placebo, renal blood flow increased and renal vascular resistance decreased significantly during the combination. Filtration fraction amounted to 22.7 +/- 1.2% during placebo and was 22.0 +/- 1.4 (NS), 20.4 +/- 1.2 (p less than 0.01), and 20.5 +/- 1.4% (p less than 0.05) during nitrendipine, cilazapril, and the combination, respectively. During nitrendipine, albuminuria was slightly higher than during placebo: 0.86 +/- 0.39 vs. 0.58 +/- 0.25 mg/min (NS). During cilazapril alone and during the combination of both drugs, albuminuria was lower as compared to nitrendipine: 0.38 +/- 0.14 mg/min (p less than 0.01) and 0.44 +/- 0.18 mg/min (p less than 0.01), respectively. The data suggest that the combination of nitrendipine and cilazapril is an effective treatment in renal hypertension. In addition, cilazapril alone as well as the combination with nitrendipine reduced albuminuria, possibly by decreasing filtration fraction and/or reduction of blood pressure.