1.
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
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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.
2.
Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial
Badve SV, Zhang L, Coombes JS, Pascoe EM, Cass A, Clarke P, Ferrari P, McDonald SP, Morrish AT, Pedagogos E, et al
Canadian Journal of Kidney Health & Disease.. 2015;2((33))
Abstract
BACKGROUND Erythropoiesis stimulating agent (ESA)-resistant anemia is common in chronic kidney disease (CKD). OBJECTIVES To evaluate the determinants of severity of ESA resistance in patients with CKD and primary ESA-resistance. DESIGN Secondary analysis of a randomized controlled trial (the Handling Erythropoietin Resistance with Oxpentifylline, HERO). SETTING AND PATIENTS 53 adult patients with CKD stage 4 or 5 and primary ESA-resistant anemia (hemoglobin <120 g/L, ESA resistance index [ERI] >1.0 IU/kg/week/gHb for erythropoietin or >0.005 mug/kg/week/gHb for darbepoeitin, no cause for ESA-resistance identified). MEASUREMENTS Iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation. METHODS Participants were divided into tertiles of ERI. Multinomial logistic regression was used to analyse the determinants of ERI tertiles. RESULTS All patients, except one, were receiving dialysis for end-stage kidney disease. The mean+/-SD ERI values in the low (n=18), medium (n=18) and high (n=17) ERI tertiles were 1.4+/-0.3, 2.3+/-0.2 and 3.5+/-0.8 IU/kg/week/gHb, respectively (P<0.001). There were no significant differences observed in age, gender, ethnicity, cause of kidney disease, diabetes, iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation between the ERI tertiles. The median [inter-quartile range] serum alkaline phosphatase concentrations in the low, medium and high ERI tertiles were 89 [64,121], 99 [76,134 and 148 [87,175] U/L, respectively (P=0.054). There was a weak but statistically significant association between ERI and serum alkaline phosphatase (R(2)=0.06, P=0.03). Using multinomial logistic regression, the risk of being in the high ERI tertile relative to the low ERI tertile increased with increasing serum alkaline phosphatase levels (P=0.02). No other variables were significantly associated with ERI. LIMITATIONS Small sample size; bone-specific alkaline phosphatase, other markers of bone turnover and bone biopsies not evaluated. CONCLUSIONS Serum alkaline phosphatase was associated with severity of ESA resistance in ESA-resistant patients with CKD. Large prospective studies are required to confirm this association. (TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry 12608000199314).