Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure

Tamirisa, Kamala P.; Aaronson, Keith D.; Koelling, Todd M.

doi:10.1016/j.ahj.2004.10.005

Cited by 87 publications

(74 citation statements)

References 22 publications

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“…Tamirisa et al 16 , when analyzing the use of spironolactone in patients with HF, found a prevalence of hyperkalemia that was very similar to the one found in the present study. A total of 926 patients were studied and 67 (7.2%) discontinued the use of spironolactone due to hyperkalemia or renal function worsening.…”

Section: Discussionsupporting

confidence: 89%

Hiperpotassemia na vigência de espironolactona em pacientes com insuficiência cardíaca descompensada

Lima¹,

Ochiai²,

Cardoso³

et al. 2008

Arq. Bras. Cardiol.

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Section: Discussionsupporting

confidence: 89%

Hiperpotassemia na vigência de espironolactona em pacientes com insuficiência cardíaca descompensada

Lima¹,

Ochiai²,

Cardoso³

et al. 2008

Arq. Bras. Cardiol.

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“…For example, the use of β-blockers has risen in patients with systolic heart failure, and the use of these medications and other inhibitors of the renin-angiotensin-aldosterone system (RAAS) may increase the risk of hyperkalemia. 30 It has been postulated that the higher rate of hyperkalemia observed with active treatment in EPHESUS versus RALES may be due to greater β-blocker use in EPHESUS. 30,31 To definitively determine whether there are any clinically meaningful differences in the risk of hyperkalemia between these two agents would require direct comparative trials, although available evidence suggests that the risk is lower with eplerenone than spironolactone when the drugs are administered at recommended doses.…”

Section: Tolerability Endocrine Effectsmentioning

confidence: 99%

“…30 It has been postulated that the higher rate of hyperkalemia observed with active treatment in EPHESUS versus RALES may be due to greater β-blocker use in EPHESUS. 30,31 To definitively determine whether there are any clinically meaningful differences in the risk of hyperkalemia between these two agents would require direct comparative trials, although available evidence suggests that the risk is lower with eplerenone than spironolactone when the drugs are administered at recommended doses. Table 2 summarizes the most important clinical considerations for the use of spironolactone and eplerenone.…”

Section: Tolerability Endocrine Effectsmentioning

confidence: 99%

A Comparison of the Aldosterone‐blocking Agents Eplerenone and Spironolactone

Struthers

Krum

Williams

2008

Clinical Cardiology

217

146

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Improved understanding of the adverse pharmacological properties of aldosterone has prompted investigation of the clinical benefits of blocking aldosterone at the receptor level. This article reviews the pharmacology, clinical efficacy, and tolerability of the two available blocking agents, spironolactone and eplerenone. A Medline search identified clinical studies assessing spironolactone and eplerenone. Priority was given to large, wellcontrolled, clinical trials and comparative studies. Pharmacological differences between spironolactone and eplerenone include lower affinity of eplerenone for progesterone, androgen, and glucocorticoid receptors; more consistently demonstrated nongenomic properties for eplerenone; and the presence of long-acting metabolites for spironolactone. Both agents effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head-to-head trials and differences between patient populations. There are differences in the tolerability profiles; spironolactone is associated with dose-dependent sexual side effects. Both agents produce dose-dependent increases in potassium concentrations, although the effect with spironolactone appears to be greater when both agents are administered at recommended doses. Choice of a specific agent should be based on individual patient issues, such as the nature of heart failure and patient concerns about adverse events.

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“…[14][15][16] Likewise, pharmacologic inhibition of the MR may cause hyperkalemia. 17 Nevertheless, despite these clinical observations and numerous experimental studies confirming the relevance of aldosterone, it becomes increasingly clear that regulation of K + homeostasis is at least in part also independent from aldosterone. [18][19][20] Indeed, the kaliuretic response to a dietary K + load occurs very rapidly and often before plasma aldosterone is elevated.…”

mentioning

confidence: 99%

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Todkar

Picard²,

Loffing‐Cueni³

et al. 2015

Journal of the American Society of Nephrology

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Aldosterone-independent mechanisms may contribute to K + homeostasis. We studied aldosterone synthase knockout (AS 2/2 ) mice to define renal control mechanisms of K + homeostasis in complete aldosterone deficiency. AS 2/2 mice were normokalemic and tolerated a physiologic dietary K + load (2% K + , 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K + intake (5% K + ), AS 2/2 mice decompensated and became hyperkalemic. High-K + diets induced upregulation of the renal outer medullary K + channel in AS 2/2 mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K + excretion was detected only with a 2% K + diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS 2/2 mice than in AS +/+ mice and was downregulated in mice of both genotypes in response to increased K + intake.Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS 2/2 mice. In contrast with the kidney, the distal colon of AS 2/2 mice did not respond to dietary K + loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K + load can be achieved in aldosterone deficiency by aldosteroneindependent activation of the renal outer medullary K + channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K + secretion and increased intratubular availability of Na + that can be reabsorbed in exchange for K + secreted.

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Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure

Cited by 87 publications

References 22 publications

Hiperpotassemia na vigência de espironolactona em pacientes com insuficiência cardíaca descompensada

Hiperpotassemia na vigência de espironolactona em pacientes com insuficiência cardíaca descompensada

A Comparison of the Aldosterone‐blocking Agents Eplerenone and Spironolactone

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

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