Tamirisa, K. P., Aaronson, K. D. & Koelling, T. K. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am. Heart J. 148, 971-978

Department of Internal Medicine, Women's L3623-0271, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA.
American heart journal (Impact Factor: 4.46). 12/2004; 148(6):971-8. DOI: 10.1016/j.ahj.2004.10.005
Source: PubMed


A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone.
We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared.
Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls.
Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.

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    • "Hyperkalemia and worsening renal function are serious adverse effects of MRAs, which are contraindicated in such cases according to current guidelines. These events are highly variable and are associated with advanced age, higher baseline potassium levels, decreased baseline renal function, diabetes mellitus and other treatments affecting potassium levels [23] [24]. Rates of hyperkalemia admissions and mortality were increased following RALES publication [25], which could also be attributed to the increasing utilization of β-blockers at that time. "
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    • "In the EMPHASIS-HF trial, the use of eplerenone reduced the risk of death from a cardiovascular cause or hospitalization for heart failure and these results were not statistically different between the subgroups of patients of older age (24% of the population studied) or less than 75 years. However, in older patients, renal function abnormalities increase the risk of hyperkalemia,[51] as well as of worsening of renal function[52] when spironolactone and eplerenone are administered. As a consequence, serum creatinine and potassium levels should be even more closely monitored in older patients. "
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    • "A small study suggested that the initiation of beta-blocker therapy was associated with preserved renal function in heart failure patients with a lower baseline GFR but not in those with a higher baseline GFR (22), although these results have yet to be confirmed. Finally, small retrospective studies have suggested that spironolactone may increase creatinine levels (23,24) and should be used cautiously in patients with reduced GFR. "
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