In patients with chronic kidney disease, spironolactone reduces major cardiovascular events but increases all-cause mortality and severe hyperkalemia
Presenter: Tz-Heng Chen, MD, Taipei Veterans General Hospital, Taipei, Taiwan
Using spironolactone to treat patients with chronic kidney disease increased their risks of all-cause mortality and severe hyperkalemia but decreased the risk major adverse cardiovascular events, driven by lower stroke risk, in this retrospective study.
In patients with chronic kidney disease (CKD), spironolactone therapy increases risks of all-cause mortality and severe hyperkalemia but reduces major adverse cardiovascular events, driven mostly by lower stroke risks, according to results of this hospital-based retrospective cohort study. The study’s aim, stated lead author Tz-Heng Chen, MD, Taipei Veterans General Hospital, Taipei, Taiwan, in a Kidney Week 2024 poster presentation, was to investigate the impact of spironolactone in patients with CKD.
Spironolactone, a potassium-sparing diuretic that binds to mineralocorticoid receptors, functions as an aldosterone antagonist and promotes sodium and water excretion and potassium retention. Prior research with steroidal mineralocorticoid receptor antagonists has demonstrated that this therapy decreases mortality in patients with heart failure with reduced ejection fraction along with effectively treating resistant hypertension and lowering proteinuria.
Their effects in patients with CKD, however, are uncertain. From hospital records, Dr. Chen and colleagues identified patients with CKD stages 3 to 5 treated from January 1, 2011, to June 30, 2023. The patients were divided into spironolactone users (n = 2,711) and nonusers (n = 5,422), with each spironolactone user matched to two nonusers based on propensity scores. End-stage renal disease (ESRD), major adverse cardiovascular events (MACEs), all-cause mortality, and severe hyperkalemia were the primary outcomes studied. Severe hyperkalemia was defined as a serum potassium level above 6.0 mmol/L. MACEs were defined as combined nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.
Compared with propensity-score matched spironolactone nonusers, spironolactone users had significantly higher risks of all-cause mortality (adjusted hazard ratio [aHR], 1.23; 95% confidence interval [CI], 1.10-1.37; P < .001) and severe hyperkalemia (aHR, 1.44; 95% CI, 1.23-1.68; P < .001). Risks of MACEs, however, was significantly lower for spironolactone users (aHR, 0.89; 95% CI, 0.81-0.98; P < .02), driven primarily by a significant reduction in stroke risk (aHR, 0.78; 95% CI, 0.70-0.87; P < .001). The risk of ESRD was similar between the two groups (aHR, 1.07; 95% CI, 0.84-1.37).
Dr. Chen concluded, “In patients with CKD, spironolactone use was associated with increased risks of all-cause mortality and severe hyperkalemia and a reduced risk of MACE, primarily driven by a decrease in stroke risk.”