High Hemoglobin Levels Maintained by an Erythropoiesis-Stimulating Agent Improve Renal Survival in Patients with Severe Renal Impairment

Our goal was to investigate the effect modification of maintaining a high Hb target range through erythropoiesis-stimulating agent therapy on the renal outcome with respect to chronic kidney disease (CKD) stage and concurrent diabetes condition in patients with CKD. We used data from a previously reported randomized controlled trial involving 321 CKD patients not on dialysis, with Hb levels of <10 g/dL, and serum creatinine (Cr) of 2.0 to 6.0 mg/dL, and in which maintaining Hb levels at 11.0-13.0 g/dL with darbepoetin-α (High Hb group) resulted in a greater renal protective effect than maintaining Hb levels at 9.0-11.0 g/dL with epoetin-α (Low Hb group). We conducted a post-hoc analysis of the effects of baseline CKD stage and concurrent diabetic condition on the renal composite endpoint, consisting of death, initiation of renal replacement therapy, and doubling of the serum Cr level. Both groups with stage 4 CKD had a 3-year cumulative renal survival rate of 53.8%, whereas in patients with stage 5 CKD, the rate in the High Hb group (31.0%) was significantly (P = 0.012) higher than that in the Low Hb group (19.1%). The observations made in patients with stage 5 CKD were maintained on further analysis of non-diabetic patients, but were not seen in those with diabetes or stage 4 CKD. These results suggest that in patients with stage 5 CKD, especially those without diabetes, achieving a higher target Hb level with erythropoiesis-stimulating agents is associated with a greater renoprotective effect.