PMID- 36396085 OWN - NLM STAT- MEDLINE DCOM- 20230327 LR - 20230425 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) VI - 81 IP - 4 DP - 2023 Apr TI - Cardiac and Kidney Adverse Effects of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Patients With CKD Not Receiving Dialysis: A Systematic Review and Meta-analysis. PG - 434-445.e1 LID - S0272-6386(22)01014-9 [pii] LID - 10.1053/j.ajkd.2022.09.014 [doi] AB - RATIONALE & OBJECTIVE: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel, orally administered agents for anemia management in chronic kidney disease (CKD). We evaluated the cardiac and kidney-related adverse effects of HIF-PHIs among patients with CKD and anemia. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & STUDY POPULATIONS: Patients with anemia and CKD not receiving maintenance dialysis. SELECTION CRITERIA FOR STUDIES: RCTs comparing HIF-PHIs to placebo or an erythropoiesis-stimulating agent (ESA) with primary outcomes of cardiac and kidney-related adverse events (AEs). DATA EXTRACTION: Two independent reviewers evaluated RCTs for eligibility and extracted relevant data. ANALYTICAL APPROACH: Dichotomous variables were pooled using the Mantel-Haenszel method and presented as risk ratios (RRs). Subgroup analyses evaluated different intervention times and HIF-PHIs, as well as phase 2 versus phase 3 trials. The certainty of findings was rated according to GRADE criteria. RESULTS: Twenty-three studies with 15,144 participants were included. No significant difference in the risk of cardiac AEs was observed between the HIF-PHIs group and the placebo (RR, 1.02 [95% CI, 0.89-1.16]; moderate certainty) or ESA (RR, 1.06 [95% CI, 0.98-1.14]; low certainty) groups. No significant difference in the risk of kidney-related AEs was observed between the HIF-PHIs group and the placebo (RR, 1.09 [95% CI, 0.98-1.20]; moderate certainty) or ESA (RR, 1.00 [95% CI, 0.94-1.06]; low certainty) groups. The occurrence of hypertension and hyperkalemia was higher in the HIF-PHIs group than in the placebo group (RRs of 1.35 [95% CI, 1.14-1.60] and 1.25 [95% CI, 1.03-1.51], respectively; both findings had high certainty). The occurrence of hypertension was lower in the HIF-PHIs group than in the ESA group (RR, 0.89 [95% CI, 0.81-0.98]; moderate certainty). LIMITATIONS: The reporting criteria of cardiac and kidney-related AEs and dosage of HIF-PHIs were inconsistent across trials. CONCLUSIONS: The occurrence of cardiac or kidney-related AEs in the HIF-PHI groups were not different compared with placebo or ESA groups. REGISTRATION: Registered at PROSPERO with registration number CRD42021228243. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Zheng, Qiyan AU - Zheng Q AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing; Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen. FAU - Wang, Yahui AU - Wang Y AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing; Fangshan Hospital Affiliated to Beijing University of Chinese Medicine, Beijing. FAU - Yang, Huisheng AU - Yang H AD - Shenzhen Maternity & Child Healthcare Hospital, Shenzhen. FAU - Sun, Luying AU - Sun L AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing; Fangshan Hospital Affiliated to Beijing University of Chinese Medicine, Beijing. FAU - Zhang, Pingna AU - Zhang P AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing. FAU - Zhang, Xueqin AU - Zhang X AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing. FAU - Guo, Jing AU - Guo J AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing. FAU - Liu, Yu Ning AU - Liu YN AD - Renal Research Institution, Beijing University of Chinese Medicine, Beijing. Electronic address: yunin1946@sina.com. FAU - Liu, Wei Jing AU - Liu WJ AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Renal Research Institution, Beijing University of Chinese Medicine, Beijing. Electronic address: liuweijing-1977@hotmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20221115 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Prolyl-Hydroxylase Inhibitors) RN - 0 (Hematinics) SB - IM MH - Humans MH - *Prolyl-Hydroxylase Inhibitors/adverse effects MH - Renal Dialysis/adverse effects MH - *Renal Insufficiency, Chronic/therapy/drug therapy MH - *Anemia/drug therapy MH - *Hypertension/drug therapy MH - *Hematinics/adverse effects MH - Kidney OTO - NOTNLM OT - Anemia OT - cardiac disorders OT - chronic kidney disease (CKD) OT - drug safety OT - erythropoiesis-stimulating agent (ESA) OT - hyperkalemia OT - hypertension OT - hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) OT - kidney-related adverse events OT - meta-analysis OT - nondialysis CKD OT - systematic review EDAT- 2022/11/18 06:00 MHDA- 2023/03/28 06:00 CRDT- 2022/11/17 19:33 PHST- 2021/12/21 00:00 [received] PHST- 2022/09/11 00:00 [accepted] PHST- 2022/11/18 06:00 [pubmed] PHST- 2023/03/28 06:00 [medline] PHST- 2022/11/17 19:33 [entrez] AID - S0272-6386(22)01014-9 [pii] AID - 10.1053/j.ajkd.2022.09.014 [doi] PST - ppublish SO - Am J Kidney Dis. 2023 Apr;81(4):434-445.e1. doi: 10.1053/j.ajkd.2022.09.014. Epub 2022 Nov 15.