A prospective observational study of early intervention with erythropoietin therapy and renal survival in non-dialysis chronic kidney disease patients with anemia: JET-STREAM Study

Abstract

Background: There is limited data showing that early treatment for anemia could prolong renal survival in non-dialysis chronic kidney disease (CKD) patients. We therefore investigated the relationship between hemoglobin (Hb) levels at initiation of epoetin beta therapy and renal outcome in non-dialysis CKD patients with anemia.

Methods: In this prospective, multi-center, observational study, non-dialysis CKD patients with anemia who were naïve to erythropoiesis-stimulating agents (ESAs) were divided into three groups based on their Hb levels at initiation of epoetin beta therapy (Group I: 10 ≤ Hb < 11 g/dL, Group II: 9 ≤ Hb < 10 g/dL, and Group III: Hb < 9 g/dL). The primary endpoint was time to first occurrence of any renal event. For the primary analysis, an inverse probability weighted Cox regression model was used to adjust time-dependent selection bias in the artificially censored data.

Results: A total of 1113 patients were eligible for primary endpoint analysis. Risk of renal events was significantly higher in Group III compared with Group I (HR, 2.52; 95 % CI, 1.98-3.21; P < 0.0001); although not significant, the risk was also higher in Group II compared with Group I (HR, 1.48; 95 % CI, 0.91-2.40; P = 0.11).

Conclusion: Initiation of ESA therapy when Hb levels decreased below 11 g/dL but not below 10 g/dL could be more effective at reducing the risk of renal events in non-dialysis CKD patients with anemia compared with initiation of ESA therapy at below 9 g/dL or even 10 g/dL.

Keywords: Anemia; Chronic kidney disease; Erythropoiesis-stimulating agents; Non-dialysis; Renal survival.

Fig. 1

Study design accounting for lead-time bias. To account for lead-time bias, the date, Hb levels, and sCr levels were confirmed at the time Hb levels decreased below 11 g/dL for the first time. Analysis was started from the point Hb levels decreased below 11 g/dL

Fig. 2

Study profile. Of 1826 patients screened, 112 were excluded because they did not receive epoetin beta treatment or they withdrew consent. The remaining 1714 patients were eligible for safety analysis in this study. 1645 patients were eligible for efficacy analysis, and 1113 patients with information on the date when Hb levels decreased below 11 g/dL were eligible for analysis of the primary endpoint. ^aNumbers of excluded patients in this figure overlap

Fig. 3

Prognosis factors for renal survival. Hb hemoglobin, sCr serum creatinine, RAS renin-angiotensin system, Ca calcium, CI confidence interval. The Cox regression model was used to assess relationships between patient baseline characteristics (including Hb levels, sCr levels, age, sex, comorbidities, and medical history; comorbidities and medical histories observed in more than 5 % of patients in each group and with less than 20 % of data missing were included) and outcomes for those patients eligible for efficacy analysis