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Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease

1,†, 1,† and 1,2,3,*
1
Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan
2
School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
3
School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2018, 7(11), 459; https://doi.org/10.3390/jcm7110459
Received: 14 November 2018 / Accepted: 19 November 2018 / Published: 21 November 2018
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Abstract

Background: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. Methods: We identified predialysis stage 3–4 chronic kidney disease (CKD) patients between 2000 and 2013 from the Longitudinal Health Insurance Database 2005 (LHID 2005). The outcomes of interest were end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), hyperkalemia-associated hospitalization (HKAH), all-cause mortality and cardiovascular mortality. The Fine and Gray sub-distribution hazards approach was adopted to adjust for the competing risk of death. Results: After the propensity score matching, 693 patients with stage 3–4 CKD were spironolactone users and 1386 were nonusers. During the follow-up period, spironolactone users had a lower incidence rate for ESRD than spironolactone non-users (39.2 vs. 53.69 per 1000 person-years) and a higher incidence rate for HKAH (54.79 vs. 18.57 per 1000 person-years). The adjusted hazard ratios for ESRD of spironolactone users versus non-users were 0.66 (95% CI, 0.51–0.84; p value < 0.001) and 3.17 (95% CI, 2.41–4.17; p value < 0.001) for HKAH. A dose-response relationship was found between spironolactone use and risk of ESRD and HKAH. There were no statistical differences in MACE, HHF, all-cause mortality and cardiovascular mortality between spironolactone users and non-users. Conclusion: Spironolactone represented a promising treatment option to retard CKD progression to ESRD amongst stage 3–4 CKD patients, but strategic treatments to prevent hyperkalemia should be enforced. View Full-Text
Keywords: chronic kidney disease (CKD); end-stage renal disease (ESRD); major adverse cardiovascular events (MACE); mortality; spironolactone chronic kidney disease (CKD); end-stage renal disease (ESRD); major adverse cardiovascular events (MACE); mortality; spironolactone
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Yang, C.-T.; Kor, C.-T.; Hsieh, Y.-P. Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease. J. Clin. Med. 2018, 7, 459.

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