Portal de Periódicos da CAPES

A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients

2019; Elsevier BV; Volume: 95; Issue: 4 Linguagem: Inglês

10.1016/j.kint.2018.11.025

1523-1755

Fabian Hammer, Uwe Malzahn, J. LEWI DONHAUSER, Christoph Betz, Markus P. Schneider, Clemens Grupp, Nils Pollak, Stefan Störk, Christoph Wanner, Vera Krane, S. Berweck, Patrick Biggar, Christoph Blaser, Thomas Bochannek, Frank Breunig, Michael Brunner, Beatrix Büschges-Seraphin, Stefan Büttner, Ahmet Çakmak, Thomas Döltz, Mara Dörken, Kai‐Uwe Eckardt, Heribert Fink, Stefan Fischer, Wolfgang Freisinger, Tilo Freiwald, Julian Gebhardt, Helmut Geiger, R. Götz, Jan Goßmann, Renate Hammerstingl, Joanna Haraźny, Michael Heckel, Andrea Heyd-Schramm, Joachim Hoyer, Rolf Janka, Oliver Jung, Markus Ketteler, Christina Klaeffling, Claudius Kleinert, Marianne Kleinert, Arnfried U. Klingbeil, Thorsten Klink, Benjamin Koch, Judith Kosowski, Michael Leidig, Jens Lutz, Mohamed Marwan, Maria Moritz, Brigitte Moye, Holger Naujoks, Kai‐Olaf Netzer, Ulrike Raff, Clemens Reichert, Imke Reimer, Jurij Ribel, Sophie Richter, Christian Ritter, Sarah Rudolf, Beate Schamberger, Michael Schmid, Thomas Schmiedeke, Andreas M. Schmitt, Heike Schneider, Reinhard Schneider, Cord Schneuzer, M Schöffauer, Lothar Schramm, Sabine Schütterle, Susanne Schwedler, Ewelina Sobkowiak, Daniel Sollinger, Frank Strutz, Sebastian Toncar, Vladimir Vasiljuk, Thomas Vogl, Thorsten Walther, Julia Weinmann‐Menke, Bettina Wirth, Hendrick Witsch, Paul Würmell, Raoul Zeltner, Josef Zimmermann,

Heart Failure Treatment and Management

Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia. Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia. In this issueKidney InternationalVol. 95Issue 4PreviewConnaughton and colleagues postulated that monogenic causes can explain many more cases of chronic kidney disease (CKD) in adults than previously assumed. Whole exome sequencing in a cohort of 114 Irish families who had 138 individuals with CKD established a molecular diagnosis in 37% of families. A CKD gene mutation was found in 36% of 78 families with a history of CKD and in 69% of 16 families with extrarenal clinical features that had only been realized in retrospect. Even when there was no family history and no extrarenal manifestations, 15% of 20 families were found to have a monogenic cause of CKD. Full-Text PDF The safety of mineralocorticoid antagonists in maintenance hemodialysis patients: two steps forwardKidney InternationalVol. 95Issue 4PreviewThe Spin-D (Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease) and MiREnDa (Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease) trials taken together provide the reassuring demonstration that up to 25 mg/d spironolactone is reasonably safe, provided maintenance hemodialysis patients are properly monitored and investigators use a per-protocol therapeutic algorithm to manage hyperkalemia. These results should encourage and reassure the investigators of the 2 currently ongoing, large, international, major-outcome clinical trials, both of which are using spironolactone up to 25 mg/d: ACHIEVE (Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease trial; NCT03020303 ) and ALCHEMIST (ALdosterone antagonist Chronic HEModialysis Interventional Survival Trial; NCT01848639 ). Full-Text PDF