Plasma Aldosterone in Hypertensive Patients on Chronic Hemodialysis: Distribution, Determinants and Impact on Survival

Kohagura, Kentaro; Higashiuesato, Yasushi; Ishiki, Tetsuya; Yoshi, Shinichiro; Ohya, Yusuke; Iseki, Kunitoshi; Takishita, Shuichi

doi:10.1291/hypres.29.597

Cited by 17 publications

(19 citation statements)

References 28 publications

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“…More important, spironolactone, 25 mg daily, in 309 Japanese hemodialysis patients reduced cardiovascular events by 60% (20). These benefits are consistent with findings suggesting that aldosterone may mediate left ventricular remodeling in dialysis recipients and that adequate antagonism of aldosterone's effects may be of benefit (5,(27)(28)(29). Although the results of these trials are promising, whether MRA improves patient-important outcomes for dialysis patients remains uncertain because of the studies' limitations (insufficient numbers of outcome events, baseline differences between groups, and high losses to followup/discontinuation rates).…”

Section: Discussionsupporting

confidence: 72%

The Safety of Eplerenone in Hemodialysis Patients

Walsh

Manns

Garg

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients.Design, setting, participants, & measurements This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events.Results Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, 24.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons .10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level .6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP.Conclusion Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis.

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Section: Discussionsupporting

confidence: 72%

The Safety of Eplerenone in Hemodialysis Patients

Walsh

Manns

Garg

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Hyperaldosteronism, both relative (with respect to expanded ECV) or absolute (defined by cutoff levels), has been documented in CKD [40][41][42] , metabolic syndrome [43,44] , and in patients treated with ACE-Is and/or ARBs (aldosterone escape) [25,26] . In the presence of subclinical ECV expansion, aldosterone excess is inappropriate and may cause nonepithelial MR activation, leading to cardiorenal proinflammatory, profibrotic changes.…”

Section: Dysregulation Of Aldosterone Secretion In Ckdmentioning

confidence: 99%

Extracellular Volume and Aldosterone Interaction in Chronic Kidney Disease

Klemmer¹,

Bomback²

2009

Blood Purif

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Since the advent of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, little attention has been given to the potential proinflammatory effects of aldosterone in high-volume states on the kidney and cardiovascular system. In order to be correctly interpreted, aldosterone levels require a volume cofactor which can now be determined by measurement of extracellular fluid volume by means of bioimpedance. Chronic kidney disease patients frequently have expanded extracellular volume (ECV) in the presence of elevated aldosterone levels. This combination may lead to cardiovascular and renal inflammation and fibrosis that can be mitigated by more precise control of ECV and/or blockade of the mineralocorticoid receptor.

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“…This is not the first study to demonstrate that ESKD patients have abnormally high aldosterone levels 30-35. Our study, however, is the first to objectively measure ECV alongside these aldosterone levels, and thus the first to demonstrate that expansion of ECV does suppress aldosterone concentration in ESKD, albeit suboptimally and to still inappropriately high levels.…”

Section: Discussionmentioning

confidence: 71%

Disordered aldosterone-volume relationship in end-stage kidney disease

Bomback

Kshirsagar

Ferris

et al. 2009

J Renin Angiotensin Aldosterone Syst

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Introduction. Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship. Materials and methods. With multifrequency bioimpedance spectroscopy, we measured total body water (TBW), extracellular volume (ECV), and intracellular volume in five haemodialysis patients at varied states of hydration and in five healthy volunteers during low-, normal-, and high-salt diets. Serum aldosterone, potassium, and C-reactive protein were measured simultaneously. Scatterplots and general estimating equations were used to examine the relationship among these variables.

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Plasma Aldosterone in Hypertensive Patients on Chronic Hemodialysis: Distribution, Determinants and Impact on Survival

Cited by 17 publications

References 28 publications

The Safety of Eplerenone in Hemodialysis Patients

The Safety of Eplerenone in Hemodialysis Patients

Extracellular Volume and Aldosterone Interaction in Chronic Kidney Disease

Disordered aldosterone-volume relationship in end-stage kidney disease

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