Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
Condition: Chronic Kidney Disease; Albuminuria
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Albuminuria
Intervention: Spironolactone; Amiloride
Intervention MeSH terms: Amiloride; Spironolactone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Mineralocorticoid Receptor Antagonists; Mineralocorticoid Effects

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.
    

Eligibility 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