Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease

Abstract

Background: Aldosterone antagonists may mediate their effects on heart failure through parathyroid hormone (PTH) in chronic kidney disease (CKD) patients. Methods: Patients with CKD on spironolactone were selected and matched for age, gender, race, use of a vitamin D analogue, the number of antihypertensive medications, and CKD stage. PTH levels before and after the first prescription of spironolactone were measured. A thorough chart review was conducted to assess for heart failure hospitalizations. An adjusted Cox proportional model was used to calculate the hazard ratio (HR) for heart failure hospitalizations among cases versus controls. Results: There were a total of 950 (mean age 67±13 years, 40% men) patients with CKD. Of these, there were 48 hospitalizations for heart failure among the cases and 82 among the controls (HR 0.37; 95% confidence interval (CI) 0.19–0.74, p =0.005). We noted a more significant decrease in PTH levels among the cases when compared to the controls ( p <0.0001). The adjusted hazard for heart failure hospitalization increased with higher PTH levels ( p =0.002) and mediation analysis revealed change in PTH level as a significant mediator of heart failure hospitalization ( p =0.04). Conclusion: Aldosterone antagonists may be helpful in preventing hospitalizations for heart failure exacerbation in CKD patients through a PTH-mediated effect.