Mineralocorticoid Receptor Antagonists in End Stage Renal Disease

Wuerzburg University Hospital118 enrolled

Overview

End stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality. Cardiovascular (CV) causes account for almost half of all-cause mortality. Increased left ventricular mass (LVM) is a common finding in ESRD patients on dialysis and is an independent predictor of survival. Yet, to date there is no established medical treatment to reduce CV morbidity and mortality in ESRD patients on hemodialysis. Blockade of aldosterone action by means of mineralocorticoid receptor antagonists (MRA) provides cardioprotection and improves outcome in heart failure patients. Furthermore, the MRA spironolactone has recently been shown to reduce LVM in patients with mild-to-moderate chronic kidney disease (CKD). The investigators here hypothesize that spironolactone treatment is cardioprotective by reducing LVM in ESRD patients on dialysis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

118

Conditions

End Stage Renal Disease / Hemodialysis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age \>18 years * Hemodialysis treatment for at least 3 months * At least 3 dialysis sessions per week * Written informed consent Exclusion Criteria: * Contraindications for cardiac magnet resonance imaging (CMR) * Mineralocorticoid receptor antagonist treatment within the last 6 months * Estimated life expectancy \< 12 months as judged by the nephrologist * History of hyperkalemia, defined as pre-dialysis potassium \> 6.5 mmol/l occurring ≥ 3 times within the last 3 months prior to enrolment. * High risk to develop hyperkalemia defined as pre-dialysis potassium \> 6.0 mmol/l * Hypotension (systolic blood pressure \< 100 mmHg) * Planned kidney transplantation (living donor) within the prospected study duration * Any acute illness within the last 4 weeks precluding a study participation as judged by the nephrologist * Non-amenorrheic women with child bearing potential without reliable contraception, pregnancy/lactation * Allergy/hypersensitivity to spironolactone * Non-compliance suspected or demonstrated

Locations (3)

University Hospital Erlangen-Nürnberg

Erlangen, Germany

University Hospital Frankfurt

Frankfurt, Germany

University Hospital Wuerzburg

Würzburg, Germany

Outcomes

Primary Outcomes

Left Ventricular Mass Index

as assessed by cardiac MRI

Time frame: 9 months

Secondary Outcomes

Cardiac function parameters

cardiac volumes, systolic and diastolic function, cardiac output as measured by cardiac MRI and echocardiography

Time frame: 9 months

Office and 24h blood pressure

Time frame: 9 months

Clinical measures of heart failure severity

New York Heart Association (NYHA) functional class, 6 minute walk test

Time frame: 9 months

Vascular function

Carotid intima meda thickness, pulse wave analysis, carotid artery distensibility, flow mediated dilatation of the brachial artery

Time frame: 9 months

Biomarkers of heart failure, inflammation and fibrosis

Time frame: 9 months

Quality of Life - Hospital Anxiety and Depression Scale (HADS)

Quality of life will be measured by analyzing HADS

Time frame: 9 months

Cardiac death and/or hospitalization for heart failure

Time frame: 9 months

Safety measures

Pre-dialysis potassium levels, frequency of hyperkalemic episodes (K\>6.5mmol/l), measurement of residual kidney function (if applicable)

Time frame: 9 months

Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36)

Quality of life will be measured by analyzing KDQOL-SF36

Time frame: 9 months