Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) on anemia in non-dialysis-depende
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NEPHROLOGY - REVIEW
Efficacy and safety of hypoxia‑inducible factor prolyl hydroxylase inhibitor (HIF‑PHI) on anemia in non‑dialysis‑dependent chronic kidney disease (NDD‑CKD): a systematic review and meta‑analysis Siliang Zhang1 · Jing Guo2 · Shuqin Xie1 · Jianwei Chen1 · Shenrun Yu3 · Yuan Yu1 Received: 25 May 2020 / Accepted: 28 September 2020 © Springer Nature B.V. 2020
Abstract Purpose HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitor) was developed to improve renal anemia. This study was to evaluate the efficiency and safety of HIF-PHI in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Methods The literature was extracted from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Wanfang database. Statistical tests and forest plots were depicted by Review Manager Version 5.3. The primary outcome was a change in hemoglobin level from baseline (ΔHb). Secondary outcomes were changes in ferritin (ΔFerritin), hepcidin (ΔHepcidin), and transferrin saturation from baseline (ΔTSAT), and adverse events (AEs). This study is registered with PROSPERO (registration number CRD42020199656). Results Ten trials were included. The results showed that HIF-PHI improved the ΔHb [SMD 3.03 (95% CI 2.10, 3.96), P < 0.00001] in NDD patients. HIF-PHI reduced hepcidin levels in the NDD patients [SMD − 1.44 (95% CI − 2.19– 0.70), P = 0.0002]. ΔFerritin values were reduced significantly in the HIF-PHI group [SMD − 1.08 (95% CI − 1.63–0.53), P = 0.0001]. However, ΔTSAT values showed no significant difference in the HIF-PHI group compared to the placebo group [SMD − 0.23 (95% CI − 0.66–0.21), P = 0.31]. In the safety assessment, HIF-PHI did not increase adverse events significantly [RR 0.98 (95% CI 0.88–1.10), P = 0.74]. Conclusion HIF-PHI improves renal anemia and iron utilization disorder in NDD-CKD patients, without significantly more adverse events. Keywords Chronic kidney disease · Renal anemia · Hypoxia-inducible factor prolyl hydroxylase inhibitor · Meta-analysis
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11255-020-02671-z) contains supplementary material, which is available to authorized users. * Yuan Yu [email protected] 1
Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Lingjiang Road, Yuzhong District, Chongqing 400010, China
2
Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing 400030, China
3
Center of Urology and Nephrology, Yongchuan People’s Hospital of Chongqing, Chongqing 402160, China
Anemia is the most common complication of chronic kidney disease (CKD), usually occurring in CKD stages 3–5. With the loss of renal function, anemia progresses to CKD. In a retrospective analysis of 933,463 NDD-CKD patients followed in the US Veterans Administration, 20.6% had anemia. Only 23.6% of patients with anemia had both TSAT and ferritin levels measured [1]. Anemia in CKD worsens the patient’s quality of life, aggravates t
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