Erythropoietin in Acute Kidney Injury (EAKI): a Pragmatic Randomized Clinical Trial

Background Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury.MethodsThis is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin <11 g/dL and acute kidney injury defined as an increase of serum creatinine of 0.3 mg/dL within 48 hours or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n=67) and the second received standard of care (control; n=67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis.ResultsThere was no statistically significant difference in transfusion need (RR=1.05, 95%CI 0.65,1.68; p=0.855), in renal recovery full or partial (RR=0.96, 95%CI 0.81,1.15; p=0.671), in need for dialysis (RR=11.00, 95%CI 0.62, 195.08; p=0.102) or in death (RR=1.43, 95%CI 0.58,3.53; p=0.440) between the erythropoietin and the control group. ConclusionsErythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).

Prophylactic Erythropoietin for Neuroprotection in Very Preterm Infants: A Meta-Analysis Update

A meta-analysis update of randomized controlled trials investigating recombinant human erythropoietin suggests improved neurodevelopmental outcome in preterm infants. There was substantial heterogeneity, which could be ascribed to a single trial. Exclusion of this trial featuring a high risk of bias abolished heterogeneity and any effects of recombinant human erythropoietin treatment.

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin

PURPOSE Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin. METHODS In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment. RESULTS A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) ( P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively ( P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone. CONCLUSION LEN restores sensitivity to recombinant erythropoietin in growth factor–insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813 ).

Lack of association between erythropoietin treatment and risk of depression in patients with end-stage kidney disease on maintenance dialysis: a nationwide database study in Taiwan

Background: Patients with end-stage kidney disease (ESKD), have been associated with higher risk of developing depression. Erythropoietin (EPO), frequently used for the treatment of anemia in ESKD patients, has been shown to have neuroprotective and antidepressant effects. In this study, we examined whether EPO treatment changed the risk of depression in ESKD patients. Methods: In a nationwide population-based cohort in Taiwan from 1998 to 2013, patients with a diagnosis of ESKD on maintenance dialysis and aged greater than 18 years were classified into EPO treatment group or non-EPO treatment group. All patients were followed up until the diagnosis of depressive disorder or the end of the study period. Results: In this cohort (13,067 patients in the EPO and 67,258 patients in the non-EPO group), 5569 patients were diagnosed as depressive disorder in the follow-up period. We found the risk of depression in EPO group was not significantly different from that in non-EPO group (adjusted hazard ratio = 0.98, 95% confidence interval 0.92–1.04, p = 0.499) after adjusting for sex, age, certification year of catastrophic illness for ESKD, physical co-morbidities, and use of benzodiazepines. Conclusion: In summary, using the nationwide reimbursement data in Taiwan, we found that EPO treatment in ESKD patients was not associated with their general risk of developing depression.