Linpei Jia1, Xingtong Dong1, Jingyan Yang2, Rufu Jia2, Hongliang Zhang3. 1. Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. 2. Central Hospital of Cangzhou, Cangzhou 061001, China. 3. Department of Life Sciences, the National Natural Science Foundation of China, Beijing 100085, China.
Abstract
BACKGROUND: Renal anemia is a severe complication of chronic kidney disease (CKD) and may worsen its prognosis. Roxadustat is the only oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has been proved effective to treat renal anemia. However, effects of roxadustat on non-dialysis-dependent CKD (NDD-CKD) have yet to be supported by evidence-based medicine. METHODS: Based on the databases of PubMed, EMBASE and Web of Science by 12 April 2019 (CRD42019133225), a meta-analysis of randomized controlled trials (RCTs) on roxadustat for treatment of NDD-CKD was conducted. Primary outcomes were parameters of hemoglobin (Hb) and Hb response. Secondary outcomes were hepcidin, ferritin, total iron binding capacity (TIBC), transferrin saturation (TAST), incidences of diarrhea, adverse events (AEs) and severe adverse events (SAEs). The risk of bias and the quality of evidence were assessed, respectively. Both continuous and binary variables were analyzed by the random effects models. Sensitivity analyses were performed when a significant heterogeneity was observed (P<0.1 and I2>50%). RESULTS: Finally, three studies with a total of 214 subjects in the roxadustat group and 80 subjects in the placebo group were enrolled. An increase of Hb [weighted mean difference (WMD) =1.22, 95% CI: 0.95 to 1.49, P<0.01], Hb response [odds ratio (OR) =27.74, 95% CI: 10.18 to 75.62, P<0.00001], and TIBC [standard mean difference (SMD) =1.59, 95% CI: 1.17 to 2.01, P<0.00001] was found. A decrease of hepcidin (SMD =-4.46, 95% CI: -5.02 to -3.89, P<0.00001), ferritin (WMD =-61.05, 95% CI: -85.70 to -36.40, P<0.00001) and TAST (WMD =-6.55, 95% CI: -8.82 to -4.29, P<0.00001) were noted as well. Analyses of incidence in diarrhea (OR =1.54, 95% CI: 0.49 to 4.79, P=0.46), AEs (OR =1.31, 95% CI: 0.76 to 2.27, P=0.34) and SAEs (OR =1.25, 95% CI: 0.29 to 5.35, P=0.76) yielded no difference between the roxadustat and the placebo groups. CONCLUSIONS: Roxadustat improved renal anemia of NDD-CKD patients by improving Hb and iron metabolism. Oral administration of roxadustat was relatively safe in that roxadustat did not increase the incidence of AEs and SAEs. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Renal anemia is a severe complication of chronic kidney disease (CKD) and may worsen its prognosis. Roxadustat is the only oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has been proved effective to treat renal anemia. However, effects of roxadustat on non-dialysis-dependent CKD (NDD-CKD) have yet to be supported by evidence-based medicine. METHODS: Based on the databases of PubMed, EMBASE and Web of Science by 12 April 2019 (CRD42019133225), a meta-analysis of randomized controlled trials (RCTs) on roxadustat for treatment of NDD-CKD was conducted. Primary outcomes were parameters of hemoglobin (Hb) and Hb response. Secondary outcomes were hepcidin, ferritin, total iron binding capacity (TIBC), transferrin saturation (TAST), incidences of diarrhea, adverse events (AEs) and severe adverse events (SAEs). The risk of bias and the quality of evidence were assessed, respectively. Both continuous and binary variables were analyzed by the random effects models. Sensitivity analyses were performed when a significant heterogeneity was observed (P<0.1 and I2>50%). RESULTS: Finally, three studies with a total of 214 subjects in the roxadustat group and 80 subjects in the placebo group were enrolled. An increase of Hb [weighted mean difference (WMD) =1.22, 95% CI: 0.95 to 1.49, P<0.01], Hb response [odds ratio (OR) =27.74, 95% CI: 10.18 to 75.62, P<0.00001], and TIBC [standard mean difference (SMD) =1.59, 95% CI: 1.17 to 2.01, P<0.00001] was found. A decrease of hepcidin (SMD =-4.46, 95% CI: -5.02 to -3.89, P<0.00001), ferritin (WMD =-61.05, 95% CI: -85.70 to -36.40, P<0.00001) and TAST (WMD =-6.55, 95% CI: -8.82 to -4.29, P<0.00001) were noted as well. Analyses of incidence in diarrhea (OR =1.54, 95% CI: 0.49 to 4.79, P=0.46), AEs (OR =1.31, 95% CI: 0.76 to 2.27, P=0.34) and SAEs (OR =1.25, 95% CI: 0.29 to 5.35, P=0.76) yielded no difference between the roxadustat and the placebo groups. CONCLUSIONS: Roxadustat improved renal anemia of NDD-CKD patients by improving Hb and iron metabolism. Oral administration of roxadustat was relatively safe in that roxadustat did not increase the incidence of AEs and SAEs. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Anatole Besarab; Elena Chernyavskaya; Igor Motylev; Evgeny Shutov; Lalathaksha M Kumbar; Konstantin Gurevich; Daniel Tak Mao Chan; Robert Leong; Lona Poole; Ming Zhong; Khalil G Saikali; Marietta Franco; Stefan Hemmerich; Kin-Hung Peony Yu; Thomas B Neff Journal: J Am Soc Nephrol Date: 2015-10-22 Impact factor: 10.121