Effect of spironolactone on K+ homeostasis and ENaC expression in lymphocytes from chronic hemodialysis patients

Michea, Luis; Vukusich, Antonio; González, Magdalena; Zehnder, C; Marusic, Elisa T.

doi:10.1111/j.1523-1755.2004.00931.x

Cited by 28 publications

(27 citation statements)

References 45 publications

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“…After full-text screening, one article was excluded as no data of serum potassium for the control group was provided. 21 Eleven studies were reported in this systematic review, among which five studies were RCTs [22][23][24][25][26] and six were non-randomized studies [27][28][29][30][31][32] ( Figure 1). …”

Section: Search Resultsmentioning

confidence: 99%

“…The studies that reported no significant difference between the MRA and placebo group used a rather low-dose of the MRA (no more than 25 mg daily of spironolactone or eplerenone). [25][26][27][28][29]31 In the trials that found a significant increase in the serum potassium level after administration of MRAs, large doses (50 mg thrice a week) of MRAs were used. 23,24,30,32 There was an exception, the trial conducted by Gross et al, 22 in which patients took spironolactone 50 mg twice daily for 2 weeks, and no significant increase in the serum potassium level was observed.…”

Section: Discussionmentioning

confidence: 99%

“…The serum potassium level at study completion was 4.9 ± 0.3 in the spironolactone group and 4.9 ± 0.7 in the control group, with no significant difference. Hussain et al, 31 Shavit et al, 29 Michea et al, 28 Gross et al, 22 Vukusich et al, 24 Feniman-De-Stefano et al 25 and Walsh et al 26 also found no significant change in the serum potassium level.…”

Section: Effect Of Mra On the Predialysis Potassium Levelmentioning

confidence: 97%

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Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

et al. 2016

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Introduction Cardiovascular disease is an important factor in the mortality and morbidity of patients with end-stage renal disease receiving hemodialysis. Although mineralocorticoid receptor antagonists may have potential benefits on the cardiovascular system, their safety for patients on hemodialysis remains unclear, considering the differences between the results of already performed clinical trials. Methods MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and PubMed databases were searched for relevant clinical trials. The Cochrane Collaboration assessment tool was employed to evaluate the quality of the randomized controlled trials. Revman 5.3 was used to perform the meta-analysis. Results Eleven studies (n¼379) were included in the systematic review and five randomized controlled trials were included in the meta-analysis (n¼248). Mineralocorticoid antagonists (MRAs) did not increase predialysis potassium levels significantly (0.11, 95% confidence interval À0.03 to 0.25, p ¼ 0.11). However, the studies included in this review reported inconsistently with respect to effects of mineralocorticoid receptor antagonists on blood pressure, left ventricular ejection fraction and left ventricular hypertrophy, and quantitative analysis was not performed due to insufficient data. One trial showed that the mineralocorticoid receptor antagonists were associated with decreased carotid intima-media thickness and other articles concluded that mineralocorticoid receptor antagonists had no effect on aortic stiffness. Conclusion It is safe to use low dose mineralocorticoid receptor antagonists on patients receiving hemodialysis, at the end of each session of hemodialysis, and close monitoring of serum potassium levels and possible side effects is necessary. The cardiovascular actions still need to be explored and large scale RCTs are in progress.

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Section: Search Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Mra On the Predialysis Potassium Levelmentioning

confidence: 97%

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Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

et al. 2016

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“…Previous studies from our group with a similar protocol have shown the effectiveness of the protocol used in the study presented here. In fact, measurements of genomic epithelial sodium channel expression in lymphocytes were returned to normal levels with the use of spironolactone (32). In the study presented here, we performed monthly plasma potassium analysis and we have not observed hyperkalemic episodes during the 2 years of spironolactone treatment.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients

Vukusich

Varela

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium.Design, setting, participants, & measurements: HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years.Results: Fifty-three age-and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 ؎ 0.07, spironolactone: 0.01 ؎ 0.04; carotid bifurcation, placebo: 0.15 ؎ 0.27, spironolactone: 0.0001 ؎ 0.01; internal carotid, placebo: 0.10 ؎ 0.12, spironolactone: ؊0.10 ؎ 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group.Conclusions: Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients.

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“…Clinical studies have indicated that 40% to 60% of chronic renal failure patients are hyperaldosteronemic. 40 Most reports prove that oxidative stress is present in end-stage renal disease patients, and oxidative stress would be a strong cofactor for the development of cardiovascular complications. 41 Considering the high prevalence of LVH in hemodialysis patients, our findings emphasize the need for clinical studies to determine the potential beneficial effects of MR blockade in patients with chronic renal failure.…”

Section: Perspectivesmentioning

confidence: 99%

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

et al. 2008

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Abstract-Chronic renal failure causes left ventricular hypertrophy, but the molecular mechanisms involved remain unknown. We, therefore, investigated whether the mineralocorticoid receptor is implicated in the cardiac hypertrophy observed in uremic rats and whether mineralocorticoid receptor blockade could be protective in chronic renal failure. Experimental groups were: control rats, uremic rats (NPX) with 5/6 nephrectomy (5 weeks), and NPX rats fed with spironolactone for 5 weeks. Systolic blood pressure was increased in both NPX rats and NPX rats fed with spironolactone for 5 weeks. Echocardiography revealed concentric left ventricular hypertrophy in uremia, which was attenuated by spironolactone. Enlarged cardiomyocyte size was observed in both left and right ventricles of NPX rats, an effect that was prevented by spironolactone. Mineralocorticoid receptor antagonism attenuated the increase of ventricular brain natriuretic peptide mRNA levels induced by nephrectomy. Left ventricular gene expressions of aldosterone synthase, mineralocorticoid receptor, and hydroxysteroid dehydrogenase type 2 were the same in the 3 groups, whereas gene expression of the glucocorticoid receptor was significantly diminished in chronic renal failure rats. No significant differences in cardiac aldosterone were observed between control rats and NPX rats, although NPX rats fed with spironolactone for 5 weeks showed increased plasma aldosterone levels. However, a significant increase in serum and glucocorticoid-inducible kinase-1 mRNA expression and protein was present in the NPX group; spironolactone treatment significantly reduced serum and glucocorticoid-inducible kinase-1 mRNA and protein in the left ventricle. Uremic rats exhibited a significant increase of superoxide production and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits expression (NOX-2, NOX-4, and p47 phox ) in the left ventricle, which was prevented by the mineralocorticoid receptor antagonist. Our findings provide evidence of the beneficial effects of spironolactone in cardiac hypertrophy and cardiac oxidative stress in chronic renal failure. (Hypertension. 2008;52:295-300.) Key Words: aldosterone Ⅲ mineralocorticoid receptor Ⅲ cardiac hypertrophy Ⅲ SGK1 Ⅲ oxidative stress Ⅲ hydroxysteroid dehydrogenase type 2

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Effect of spironolactone on K+ homeostasis and ENaC expression in lymphocytes from chronic hemodialysis patients

Abstract: Spironolactone may be considered for the treatment of selected chronic HD patients. The effect of the drug on a known target of aldosterone, the ENaC, demonstrates the effectiveness of the drug to block aldosterone effects in nonepithelial tissues.

Cited by 28 publications

References 45 publications

Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients

Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

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