Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease

• Status: Completed
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Vascular endothelial dysfunction increases cardiovascular (CV) risk and contributes to the progression of chronic kidney disease (CKD). Mineralocorticoid receptor (MR) antagonists have been shown to improve endothelial function, as well as decrease CV mortality and proteinuria. The specific biochemical pathways that produce these pharmacological effects for MR antagonists, however, are poorly understood. This study investigates the effect of MR antagonism on endothelial function in patients with moderate (stage III) CKD using a randomized, controlled trial. Three specific aims are proposed: Aim 1: To determine if spironolactone improves endothelial function as compared to amiloride in patients with stage III CKD; Aim 2: To determine if oxidative stress is associated with changes in endothelial function by spironolactone compared to amiloride in patients with stage III CKD; and Aim 3: To determine if endothelial dysfunction contributes to albuminuria in patients with stage III CKD. The clinical relevance is to improve understanding of the mechanisms of kidney function decline in CKD in order to develop interventions to delay or prevent dialysis, which would translate into alleviating patient suffering, caregiver burden, and health care costs.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborator: National Institutes of Health (NIH)
• Treatments: Amiloride; Mineralocorticoid Receptor Antagonists; Mineralocorticoids; Spironolactone

Criteria

Inclusion Criteria:

• Adults (18-65 years of age)

• CKD (eGFR 25-60 mL/min/1.73m2) with urine albumin-to-creatinine ratio > 30 mg/g

• CKD (eGFR > 60 mL/min/1.73m2) with urine albumin-to-creatinine ratio ≥ 300 mg/g

Exclusion Criteria:

• Severe hypertension (HTN) (office BP ≥ 160/100 mm Hg)

• Hypotension (office BP < 110/70 mm Hg)

• Serum potassium > 5 milliequivalent/L

• History of arrhythmia, including atrial fibrillation

• Pregnant or breast feeding woman

• Diabetes mellitus (DM) type 1

• Diabetes mellitus type 2 with glycosylated hemoglobin ≥ 6.5%

• Dementia or cognitive impairment prohibiting consent

• History of ischemic stroke, unstable angina, or myocardial infarction within the past 6 months

• Allergy or intolerance to spironolactone or amiloride

• Use of an MR antagonist or an epithelial sodium channel blocking medication within the last month

• Known primary aldosteronism or renal artery stenosis