-
1.
Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis
Fu Z, Geng X, Chi K, Song C, Wu D, Liu C, Hong Q
Frontiers in pharmacology. 2022;13:746265
-
-
-
Free full text
-
Editor's Choice
Abstract
Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.
PICO Summary
Population
People with chronic kidney disease (CKD) with or without dialysis, suffering from anaemia and participating in randomised controlled trials (RCTs), (n= 7,933, 7 RCTs).
Intervention
Various doses of daprodustat.
Comparison
Recombinant human erythropoietin (rhEPO).
Outcome
For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in haemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD)= -0.01, 95% confidence interval (CI)= -0.38, 0.35; MD= 0.15, 95% CI= -0.29, 0.60; respectively). In addition, a significant increase in transferrin saturation, total iron binding capacity and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients. As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR)= 0.99, 95% CI= 0.92, 1.06), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR= 1.04, 95% CI= 1.01,1.07), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result.
-
2.
Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis
Huang Q, Liao Z, Liu X, Xia Y, Wang J
International urology and nephrology. 2022
Abstract
OBJECTIVE As a novel oral agent in treating anemia of chronic kidney disease (CKD), several clinical trials of vadadustat have been conducted to compare with darbepoetin alfa. This study systematically reviews and investigates the efficacy and safety of vadadustat in the anemia treatment with different duration in both nondialysis-dependent CKD (NDD-CKD) and dialysis-dependent CKD (DD-CKD). METHODS Several main databases were searched for randomized controlled trials (RCTs) reporting vadadustat vs darbepoetin alfa for anemia patients with CKD. The outcome indicators were focused on hemoglobin (Hb), the percentage of patients within the target Hb, the need for RBC (Red Blood Cell) transfusions, and serious adverse events (SAEs). RESULTS Four eligible studies with 8,026 participants were included. The changes of Hb levels from the baseline in the darbepoetin alfa group were significantly higher than that in the vadadustat group with DD-CKD (mean difference (MD) - 0.19, [95% confidence interval (CI), - 0.21 to - 0.17], p < 0.0001). In NDD-CKD patients, the changes of Hb levels in the two groups are not significantly different (MD = - 0.06, [95% CI, - 0.18 to 0.05], p = 0.006), especially, during the treatment duration of 20-36 weeks (MD = 0.02, [95% CI, - 0.04 to 0.08], p = 0.51). The percentage of patients within the target Hb was significantly lower in the vadadustat group than that in the darbepoetin alfa group in DD-CKD patients (MD = 0.9, [95% CI, 0.86 to 0.94], p < 0.00001), while in NDD-CKD patients, there was no significant difference (MD = 1.05, [95% CI, 0.99 to 1.12], p < 0.00001). In terms of safety, the two agents had no significant difference in the incidence of RBC transfusions and SAEs (RR = 1.26 [95% CI, 0.99 to 1.61], p = 0.52; RR = 0.97, [95% CI, 0.94 to 1.01], p = 0.19; respectively). CONCLUSION Compared to darbepoetin alfa, vadadustat had the same effect in raising the hemoglobin level in NDD-CKD patients in the short term. Vadadustat may become an effective and safe alternative for the treatment of patients with anemia and CKD, especially in NDD-CKD patients. As the application of vadadustat is still under exploration, future research should compensate for the limitations of our study to estimate the vadadustat's value.
-
3.
Risk of infection in roxadustat treatment for anemia in patients with chronic kidney disease: A systematic review with meta-analysis and trial sequential analysis
Chong S, Xie Q, Ma T, Xiang Q, Zhou Y, Cui Y
Frontiers in pharmacology. 2022;13:967532
Abstract
Background: Many studies demonstrated that roxadustat (FG-4592) could increase hemoglobin (Hb) levels effectively in anemia patients with chronic kidney disease (CKD). However, its safety remains controversial. This study aims to explore the risk of infection for CKD patients treated with roxadustat, especially focused on sepsis. Methods: We thoroughly searched for the randomized controlled trials (RCTs) comparing treatment with roxadustat versus erythropoiesis stimulating agents (ESAs) or placebo in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, European Union Clinical Trials Register. Both on and not on dialysis anemia patients with CKD were included. Primary outcomes contained the incidence rates of sepsis. Secondary outcomes included infection-related consequences (septic shock and other infection events), general safety outcomes [all-cause mortality, treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)] and iron parameters. Moreover, a trial sequential analysis (TSA) was conducted to assess if the results were supposed to be a robust conclusion. Results: Eighteen RCTs (n = 11,305) were included. Overall, the incidence of sepsis (RR: 2.42, 95% CI [1.50, 3.89], p = 0.0003) and cellulitis (RR: 2.07, 95% CI [1.24, 3.44], p = 0.005) were increased in the roxadustat group compared with placebo group. In non-dialysis-dependent (NDD) CKD patients, the incidence of cellulitis (RR 2.01, 95% CI [1.23, 3.28], p = 0.005) was significantly higher in roxadustat group than that in the ESAs or placebo group. Both groups showed similar results in the incidence of septic shock (RR 1.29, 95% CI [0.86, 1.94], p = 0.22). A significant increased risk of all-cause mortality [risk ratios (RR): 1.15, 95% confidence interval (CI) [1.05, 1.26], p = 0.002] was found in roxadustat treatment, and TSA confirmed the result. Compared with ESAs or placebo, both the incident rates of TEAEs (RR:1.03, 95% CI [1.01, 1.04], p = 0.008) and TESAEs (RR: 1.06, 95% CI [1.02, 1.11], p = 0.002) were significantly increased in roxadustat group. As for iron parameters, changes from baseline (Δ) of hepcidin (MD: -26.46, 95% CI [-39.83, -13.09], p = 0.0001), Δ ferritin and Δ TSAT were remarkably lower in the roxadustat group, while Δ Hb, Δ iron and Δ TIBC increased significantly versus those in ESAs or placebo group. Conclusion: We found evidence that incidence rates of sepsis and cellulitis are higher in roxadustat group compared with placebo. This may be the result of improved iron homeostasis. The risk of all-cause mortality, TEAEs and TESAEs in CKD patients also increased in patients treated with roxadustat. We need more clinical and mechanistic studies to confirm whether roxadustat really causes infection.
-
4.
The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials
Abdelazeem B, Shehata J, Abbas KS, El-Shahat NA, Malik B, Savarapu P, Eltobgy M, Kunadi A
PloS one. 2022;17(4):e0266243
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. METHODS Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their 95% confidential intervals (CIs). RESULTS Nine RCTs included a total of 3,175 patients in the ROX group and 2,446 patients in the control group. When compared the control group, ROX increased Hb level significantly (SMD: 1.65; 95% CI: 1.08, 2.22; P< 0.00001) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14; P = 0.0006), TSAT (SMD: -0.19; 95% CI: -0.32, -0.07; P = 0.003), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39; P< 0.0001) and increasing TIBC (SMD: 0.99; 95% CI: 0.76, 1.22; P< 0.00001) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71; P< 0.00001). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13; P = 0.01), deep venous thrombosis (DVT) (RR: 3.80; 95% CI: 1.5, 9.64; P = 0.08), and hypertension (HTN) (RR: 1.37; 95% CI: 1.13, 1.65; P = 0.001). CONCLUSION We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN. Our results support the use of ROX for NDD-CKD patients with anemia. However, higher-quality RCTs are still needed to ensure its safety and risk of thrombosis.
PICO Summary
Population
People with non-dialysis-dependent chronic kidney disease who took part in randomised controlled trials (RCTs) identified by a systematic review (n= 5,621, 9 RCTs).
Intervention
Roxadustat at various doses (ROX, n= 3,175).
Comparison
Placebo or control treatment [Darbepoetin Alfa], (n= 2,446).
Outcome
When compared the control group, ROX increased Haemoglobin level significantly (standardised mean difference [SMD]: 1.65; 95% CI: 1.08, 2.22) and improved iron utilization parameters by decreasing ferritin (SMD: -0.32; 95% CI: -0.51, -0.14), transferrin saturation (SMD: -0.19; 95% CI: -0.32, -0.07), and hepcidin (SMD: -0.74; 95% CI: -1.09, -0.39) and increasing total iron binding capacity (SMD: 0.99; 95% CI: 0.76, 1.22) and transferrin (SMD: 1.20; 95% CI: 0.70, 1.71). As for safety, ROX was associated with higher serious adverse effects (RR: 1.07; 95% CI: 1.01, 1.13), deep venous thrombosis (RR: 3.80; 95% CI: 1.5, 9.64), and hypertension (RR: 1.37; 95% CI: 1.13, 1.65).
-
5.
Use of erythropoiesis-stimulating agents in children with chronic kidney disease: a systematic review
Bruce G, Schulga P, Reynolds BC
Clinical kidney journal. 2022;15(8):1483-1505
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Erythropoiesis-stimulating agents (ESAs) revolutionized the management of anaemia in chronic kidney disease (CKD) when introduced in the late 1980s. A range of ESA types, preparations and administration modalities now exist, with newer agents requiring less frequent administration. Although systematic reviews and meta-analyses have been published in adults, no systematic review has been conducted investigating ESAs in children. METHODS The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for the conduct of systematic reviews was used. All available literature on outcomes relating to ESAs in children with CKD was sought. A search of the MEDLINE, CINAHL and Embase databases was conducted by two independent reviewers. Inclusion criteria were published trials in English, children with chronic and end-stage kidney disease and use of any ESA studied against any outcome measure. An assessment of risk of bias was carried out in all included randomized trials using the criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Two tables were used for data extraction for randomized and observational studies. Study type, participants, inclusion criteria, case characteristics, follow-up duration, ESA type and dosage, interventions and outcomes were extracted by one author. RESULTS Of 965 identified articles, 58 were included covering 54 cohorts. Six were randomized trials and 48 were observational studies. A total of 38 studies assessed the efficacy of recombinant human erythropoietin (rHuEPO), 11 of darbepoetin alpha (DA) and 3 of continuous erythropoietin receptor activator (CERA), with 6 studies appraising secondary outcome measures exclusively. Recruitment to studies was a consistent challenge. The most common adverse effect was hypertension, although confounding effects often limited direct correlation. Two large cohort studies demonstrated a greater hazard of death independently associated with high ESA dose. Secondary outcome measures included quality of life measures, growth and nutrition, exercise capacity, injection site pain, cardiovascular function, intelligent quotient, evoked potentials and platelet function. CONCLUSIONS All ESA preparations and modes of administration were efficacious, with evidence of harm at higher doses. Evidence supports individualizing treatments, with strong consideration given to alternate treatments in patients who appear resistant to ESA therapy. Further research should focus on randomized trials comparing the efficacy of different preparations, treatment options in apparently ESA-resistant cohorts and clarification of meaningful secondary outcomes to consolidate patient-relevant indices.
PICO Summary
Population
Children with chronic kidney disease using any erythropoiesis-stimulating agents (ESAs), (58 studies, n= 3,895).
Intervention
Systematic review assessing the efficacy of ESAs.
Comparison
Outcome
A total of 38 studies assessed the efficacy of recombinant human erythropoietin, 11 of darbepoetin alpha, and 3 of continuous erythropoietin receptor activator, with 6 studies appraising secondary outcome measures exclusively. The most common adverse effect was hypertension, although confounding effects often limited direct correlation. Two large cohort studies demonstrated a greater hazard of death independently associated with high ESA dose. Secondary outcome measures included quality of life measures, growth and nutrition, exercise capacity, injection site pain, cardiovascular function, intelligent quotient, evoked potentials and platelet function.
-
6.
The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review
Qie S, Jiao N, Duan K, Li J, Liu Y, Liu G
International urology and nephrology. 2021
Abstract
BACKGROUND Anemia is a common complication for patients with kidney disease. Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), which is a newly approved oral drug for anemia. We performed this study to build evidence regarding efficacy and safety of roxadustat in kidney disease patients with or without dialysis. METHODS We searched the databases of PubMed, Embase, Cochrane library and clinicaltrials.gov from the inception to July 20, 2020. The randomized controlled trials (RCTs) which compared roxadustat with placebo or other therapies in the treatment of anemia in kidney disease patients were included. Data were extracted from eligible studies and pooled in a meta-analysis model using RevMan5.3 and stata13.0 software. RESULTS Eight RCTs with 1010 patients were included in our analysis. We found that roxadustat significantly increased hemoglobin (Hb) level (1.10 g/dL, 95% CI [0.52 g/dL, 1.67 g/dL], p = 0.0002), total iron-binding capacity (TIBC) (58.71 µg/dL, 95% CI [44.10 µg/dL, 73.32 µg/dL], p < 0.00001), iron level (9.28 µg/dL, 95% CI [0.11 µg/dL, 18.45 µg/dL], p = 0.05) compared with control group in kidney disease patients. In addition, our result showed that a significant reduction in hepcidin level (- 31.96 ng/mL, 95% CI [- 35.05 ng/mL, - 28.87 ng/mL], p < 0.00001), ferritin (- 44.82 ng/mL, 95% CI [- 64.42 ng/mL, - 25.23 ng/mL], p < 0.00001) was associated with roxadustat. No difference was found between roxadustat and control group in terms of oral iron supplementation, adverse events (AEs), serious adverse events (SAEs), infection, myocardial infraction, stroke, heart failure and death. CONCLUSIONS Roxadustat has higher mean Hb level than placebo or EPO. Due to the short follow-up period and the lack of critical data, more RCTs are needed to prove long-term safety and effectiveness of roxadustat in the future.
-
7.
The Effect of Iron Supplementation on FGF23 in Chronic Kidney Disease Patients: a Systematic Review and Time-Response Meta-Analysis
Abu-Zaid A, Magzoub D, Aldehami MA, Behiry AA, Bhagavathula AS, Hajji R
Biological trace element research. 2021;199(12):4516-4524
Abstract
Fibroblast growth factor 23 (FGF23) gene is found to be responsible for autosomal dominant hypophosphatemic rickets, and is highly expressed in chronic kidney disease (CKD) and end-stage renal disease patients with iron deficiency anemia (IDA). We evaluated the efficacy of different iron treatments on FGF23 levels in dialysis-dependent and non-dialysis-dependent CKD patients with IDA. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing different types of iron treatment versus placebo in CKD patients up to May 2020. We investigated the efficacy of iron treatment on the levels of FGF23 and C-terminal FGF23 (cFGF23) in CKD patients. We estimated weighted mean differences (WMDs) and 95% confidence intervals (CIs) using the random-effects model. Nine studies with 11 arms were included in the meta-analysis. Overall, iron treatment showed a significant reduction in FGF23 levels compared to control group (WMD: - 60.56 pg/ml, 95% CI: - 92.17, - 28.95). Compared to placebo, subgroup analysis showed that oral iron therapy (WMD: - 6.98 pg/ml, 95% CI: - 10.66, - 3.31) was more effective than intravenous (IV) iron therapy (WMD: 4.90 pg/ml, 95% CI: - 12.03, 21.83) on FGF23 levels. There was no significant change in cFGF23 levels between iron treatment and control group (WMD: - 64.72 Ru/ml, 95% CI: - 147.69, 18.25). Subgroup analysis showed that oral iron therapy resulted in a significant reduction in cFGF23 levels compared to control group (WMD: - 150.48 RU/ml, 95% CI: - 151.31, - 149.65). In conclusion, iron treatment was associated with a significant decrease in FGF23 levels in CKD patients.
-
8.
Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis
Zhang L, Hou J, Li J, Su SS, Xue S
Aging. 2021;13
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Anemia is a common complication of chronic kidney disease (CKD). Treating renal anemia with erythropoiesis-stimulating agents (ESAs) or erythropoietin analogs is effective but has side effects. Therefore, we performed a meta-analysis to assess the efficacy and safety of roxadustat in treating CKD-induced anemia. METHODS We searched publications online and conducted a meta-analysis and calculated relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with 95% CIs for continuous data. RESULTS Of 110 articles, nine were included that contained 12 data sets and 11 randomized control trials on roxadustat. In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in hemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group (P<0.0001, P=0.001, respectively). The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (P<0.00001, MD=6.92, 95% CI: 4.03, 11.89). However, in the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group. Hyperkalemia may be a side effect of roxadustat. CONCLUSIONS Roxadustat elevated the serum Hb levels in a manner similar to that observed for ESAs. Roxadustat raised the Hb levels more significantly than the placebo and showed a higher Hb response rate than the placebo group in NDD patients. Roxadustat is a safe and effective drug for anemia in CKD patients.
PICO Summary
Population
Patients with chronic kidney disease-induced anaemia (9 studies).
Intervention
Roxadustat.
Comparison
Erythropoiesis-stimulating agents (ESAs) or erythropoietin analogues or placebo.
Outcome
In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in haemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group. The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (MD=6.92). In the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group.
-
9.
The efficacy of Roxadustat for the treatment of anemia in dialysis dependent chronic kidney disease patients: an updated systematic review and meta-analysis of randomized clinical trials
Abdelazeem B, Abbas KS, Shehata J, El-Shahat NA, Baral N, Savarapu P, Kunadi A
Annals of translational medicine. 2021;9(23):1714
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Anemia is a common complication in chronic kidney disease (CKD) with increased morbidity and mortality. Recently published RCTs were conducted to compare the effect of the new medication roxadustat (ROX) with erythropoiesis-stimulating agent (ESA) in dialysis-dependent CKD (DD-CKD) patients. Our article aimed to meta-analyze published RCTs to investigate the efficacy and safety of ROX for anemia in DD-CKD patients and update the effect of the new studies on overall analysis with subsequent impact on management. METHODS Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were searched systematically from inception to July 2021 by using this search term (Roxadustat OR ASP1517 OR FG4592 OR "FG-4592") AND (kidney OR renal) AND (Anemia). We only included randomized control trials (RCTs) that reported the primary outcome of change in hemoglobin (Hb) level and iron utilization parameters, including ferritin, serum iron, TSAT, TIBC, transferrin, and hepcidin. RESULTS Ten RCTs were finally included with 3031 patients in the ROX group and 2737 patients in the control group. ROX was associated with increase in Hb level (SMD: 0.2; 95% CI: 0.02, 0.39; P=0.03), TIBC (SMD: 0.79; 95% CI: 0.61, 0.98; P<0.00001), serum iron (SMD: 0.27; 95% CI: 0.18, 0.36; P<0.00001), transferrin (SMD: 0.98; 95% CI: 0.81, 1.15; P<0.00001) and decrease in hepcidin (SMD: -15.53; 95% CI: -28.07, -3.00; P<0.02) when compared with control group. There was no difference between ROX and the control group regarding ferritin level and TSAT. Sensitivity analysis by removing the most recent studies, Chen et al. or Hou et al. did not show significant difference in regard to change in Hb level. There was no difference between both groups regarding the serious side effects. However, ROX showed higher TEAEs when compared to the control group (RR: 1.03; 95% CI: 1.01, 1.05; P=0.002). DISCUSSION Our updated meta-analysis concluded that ROX increased Hb level and improved iron utilization parameters in DD-CKD patients, but ROX was associated with higher TEAEs. Our results support the use of ROX for DD-CKD patients with anemia. However, higher-quality RCTs are still needed to confirm the results of our review.
PICO Summary
Population
People with dialysis-dependent chronic kidney disease who took part in randomised controlled trials (RCTs) identified by a systematic review (n= 5,768, 10 RCTs).
Intervention
Roxadustat at various doses (ROX, n= 3,031).
Comparison
Various control treatments [darbepoetin alfa; recombinant human erythropoietin or erythropoiesis-stimulating agent], (n= 2,737).
Outcome
ROX was associated with increase in haemoglobin level (standardised mean difference [SMD]: 0.2; 95% CI: 0.02, 0.39), total iron-binding capacity (SMD: 0.79; 95% CI: 0.61, 0.98), serum iron (SMD: 0.27; 95% CI: 0.18, 0.36), transferrin (SMD: 0.98; 95% CI: 0.81, 1.15) and decrease in hepcidin (SMD: -15.53; 95% CI: -28.07, -3.00) when compared with control group. There was no difference between ROX and the control group regarding ferritin level and transferrin saturation. Sensitivity analysis by removing the most recent studies, Chen et al. or Hou et al. did not show significant difference in regard to change in Hb level. There was no difference between both groups regarding the serious side effects. However, ROX showed higher treatment emergent adverse events when compared to the control group (RR: 1.03; 95% CI: 1.01, 1.05).
-
10.
Ferric citrate in the management of hyperphosphatemia and iron deficiency anemia: A meta-analysis in patients with chronic kidney disease
Choi YJ, Noh Y, Shin S
Br J Clin Pharmacol. 2020
Abstract
BACKGROUND Phosphate-lowering effects of ferric citrate were reported in several clinical trials, but mostly in small-scale studies. The aim of this meta-analysis was to investigate the efficacy and safety of ferric citrate in controlling hyperphosphatemia and iron-deficiency anemia in chronic kidney disease (CKD) patients. METHODS PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled CKD patients receiving ferric citrate for hyperphosphatemia. Two investigators performed systematic literature search to identify eligible studies, evaluated risk of bias, and extracted relevant data. RESULTS Sixteen studies were included in meta-analysis. Phosphate-lowering effects of ferric citrate were greater compared to no active treatment (SMD=-1.15; p<0.001) and comparable to other phosphate binders (SMD=0.03; p=0.61). Calcium concentrations post ferric citrate treatment did not differ versus no active treatment (SMD=0.15; p=0.21) but significantly lower versus other phosphate binders (SMD=-0.14; p=0.01). These led to significant reductions in calcium-phosphorus product with ferric citrate versus no active control (SMD=-1.02; p<0.001) but no difference versus active control (SMD=-0.01; p=0.93). Intact parathyroid hormone showed no substantial between-group difference in both comparison against no active and active controls. Ferric citrate improved iron stores and anemia parameters, but increased risk of diarrhea, abdominal pain, and discolored feces. CONCLUSION Ferric citrate was effective in lowering phosphorus and phosphorus-calcium product versus no active treatment and had comparable effects versus other phosphate binders. Calcium levels were significantly lower with ferric citrate than with other phosphate-lowering treatment. Ferric citrate had additive effects on iron repletion and anemia control and was associated with mostly gastrointestinal side effects.
