Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials

Abstract

BackgroundPatients with end-stage renal disease (ESRD) are characterized with high risk of heart failure. Although mineralocorticoid receptor antagonists have beneficial effect on relieving cardiac fibrosis and, thus, reduce the incidence of cardiovascular disease and cardiac death, the therapeutic benefits and adverse effects are still controversial. We conducted a meta-analysis to measure the safety and efficacy of spironolactone in patients undergoing dialysis.MethodsA systematic search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Cochrane databases. Primary outcomes included changes in all-cause mortality (ACM), serum potassium concentration, incidence of hyperkalemia and gynecomastia (GYN). Secondary outcomes included changes in blood pressure (BP), left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Subgroup analysis and sensitivity analysis were further conducted. This research was registered with PROSPERO (International Prospective Register of Systematic Reviews; No. CRD42021287493).ResultsFifteen RCTs with 1,258 patients were enrolled in this pooled-analysis. Spironolactone treatment significantly decreased ACM (RR = 0.42, P < 0.0001), CCV (RR = 0.54, P = 0.008) and LVMI (MD = −6.28, P = 0.002), also increased occurrence of GYN (RR = 4.36, P = 0.0005). However, LVEF (MD = 2.63, P = 0.05), systolic BP (MD = −4.61, P = 0.14) and diastolic BP (MD = −0.12, P = 0.94) did not change between two groups after treatment. Although serum potassium concentration was increased (MD = 0.22, P < 0.0001) after spironolactone supplement, the risk of hyperkalemia remained unchanged (RR = 1.21, P = 0.31). Further subgroup analysis found more obvious advantageous as well as disadvantageous effects in Asian subjects than European or American ones. Also, with more than 9 months of treatment duration, patients achieved more favorable influence than shorter duration.ConclusionsThese results highlight the therapeutic effects of spironolactone on cardiovascular indexes, including ACM, CCV, and LVMI. However, the unignorable increase of GYN incidence and serum potassium level indicate that close monitor in dialysis-dependent patients, especially Asian patients, is essential.

Gender and race disparities in the prevalence of chronic kidney disease among individuals with hypertension in the United States, 2001–2016

“…Hypertension is a cause and a factor in the progression of CKD ( 21 , 22 ). A decline in eGFR is associated with the activation of the RAAS, which exacerbates salt and water retention and heightens salt sensitivity ( 23 ). We observed that the CKD stage in the hypertensive population remained relatively stable from 2001–2016.…”

Effect of spironolactone on survival in patients undergoing maintenance hemodialysis

“…A post-hoc study using data from the SPin-D trial also showed a higher risk of bradycardia or conduction block in patients with spironolactone use than in those without [14]. A recent meta-analysis that analyzed 15 randomized studies showed better results in terms of all-cause mortality, CCV disease events, LVMI, and LVEF in patients with spironolactone use than in those without [15]. However, the results were conflicting among studies.…”

“…showed favorable results of spironolactone on clinical outcomes [10,11,15]. However, most randomized studies had small sample sizes and some studies showed a high risk of complications of gynecomastia, hyperkalemia, or arrhythmia by spironolactone [10][11][12][13][14].…”

Consenso de la Sociedad Latinoamericana de Nefrología e Hipertensión en relación con el papel de los antagonistas del receptor mineralocorticoide en enfermedad renal crónica

“…Resultados similares describió un metaanálisis que incluyó a pacientes en HD y en diálisis peritoneal en los que se comparó el efecto de antagonistas de aldosterona frente a placebo o terapia convencional. En ellos es destacable la gran reducción de eventos cardiovasculares y de mortalidad total conseguidos por los antagonistas de la aldosterona en pacientes con ERC en diálisis si los comparamos con los observados en sujetos con ERC que no están en diálisis 51 . Sin embargo hay que tener en cuenta las limitaciones de los estudios incluidos (un diseño abierto de algunos, escaso número de pacientes, un seguimiento corto, pocos eventos de mortalidad cardiovascular, así como mucha variabilidad del riesgo relativo demostrada por análisis de sensibilidad).…”