Low Hemoglobin Levels and Hypo‐Responsiveness to Erythropoiesis‐Stimulating Agent Associated With Poor Survival in Incident Japanese Hemodialysis Patients

Abstract

Although erythropoiesis-stimulating agents (ESAs) are effective at treating anemia, the association between hemoglobin (Hb) levels and survival is still unclear, especially for the incident Japanese hemodialysis (HD) population. The Japan Erythropoietin Treatment (JET) Study is an open multi-center, prospective, observational study designed to evaluate the relationship between the maintenance of Hb levels and new HD patient prognosis after the first administration of epoetin beta. Landmark analyses were performed to examine the relationship between Hb levels at 6 months and survival. Among a total of 10,310 patients, 6631 completed the initial 6 months of epoetin beta treatment (induction phase) and were followed up for a further 2.5 years (maintenance phase). Three-year survival rate of patients with <9 g/dL Hb levels after 6 months was 74.1%, which was significantly lower than 89.3% for patients with Hb levels 10 to 11 g/dL; the adjusted hazard ratio (HR) was 2.08 (95% CI, 1.57-2.77; P < 0.0001). Moreover, the 3-year survival rate for poor responders defined by Hb levels <10 g/dL and weekly epoetin beta doses ≥ 9000 IU during the induction phase was 71.6%, which was significantly lower than 89.4% for the group, which had Hb levels 10 to 11 g/dL excluding poor responders and those with excursion; the HR was 1.71 (95% CI, 1.13-2.60; P = 0.0118). Adverse events related to the treatment were reported in 71 of 10,310 patients (0.69%). These findings suggest that the achieved low Hb levels and poor response to ESA therapy are significantly associated with high mortality.

Predictors of long-term survival of hemodialysis patients in Hamadan province, west of Iran

“…Evidence shows that maintaining the hemoglobin level of HD patients at the normal range, is associated with increase in quality of life (27), improvement of cardiac and brain function (28,29) and decrease in hospitalization and cost of treatment (30). Our study confirmed the previous findings that, low serum albumin is related with severe survival (14,31,32). Combe et al showed that decreased serum albumin over time correlated with increased CVD death (33).…”

“…Five years survival rate for HD patients in Northern part of Iran was 23%, while in southern region of Iran was 46.8% (9,10). Various factors such as albumin and hemoglobin levels, adequacy of dialysis, dialysis duration, method of RRT, body mass index (BMI), etiology of kidney failure, comorbid diseases (i.e., diabetes mellitus, cardiovascular disease), and infection rates adversely affect the survival rates of HD patients (11)(12)(13)(14)(15)(16)(17). Among all the aforementioned factors, cardiovascular disease (CVD) is considered as a leading cause of morbidity and mortality among HD patients (18,19).…”

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…However, the risk of death was significantly lower in nondiabetic patients with Ht levels ≥33% than in those with Ht levels <27% [18]. In the JET study, while there was no significant difference in the risk of death between patients with Hb levels of 10-11 g/dL and those with Hb levels of 11-12 or >12 g/dL, the best result was obtained in patients with Hb levels of 11-12 g/dL, and the risk of death slightly increased in patients with Hb levels of >12 g/dL [19].…”

“…The conventional lower limit of the target Hb level range, 10 g/dL, seems to be appropriate according to the results of observational studies conducted in Japan [16][17][18][19]. In the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS), Akizawa et al [17] reported the relationship between the Hb level at the start of observation and the risk of death in 5398 HD patients in Japan.…”

“…Furthermore, in the Japan Erythropoietin Treatment (JET) study, in which the survival prognosis in patients with different Hb levels was compared with that in the control group (patients with Hb levels of 10-11 g/dL), the survival rate was significantly lower in the group with Hb levels of <9 g/dL [19].…”