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J Clin Med. 2018 Nov 21;7(11). pii: E459. doi: 10.3390/jcm7110459.

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

Author information

1
Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan. 149054@cch.org.tw.
2
Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan. 179297@cch.org.tw.
3
Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan. 102407@cch.org.tw.
4
School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 102407@cch.org.tw.
5
School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan. 102407@cch.org.tw.

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.

KEYWORDS:

chronic kidney disease (CKD); end-stage renal disease (ESRD); major adverse cardiovascular events (MACE); mortality; spironolactone

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