Current management of renal anemia in patients with chronic kidney disease at the predialysis stage

Objective: Patients with chronic kidney disease (CKD) are frequently complicated by renal anemia as renal function declines. However, clinical guidelines on erythrocyte stimulating agents (erythropoietin : EPO) for such patients have not been established. Current clinical practice for EPO administration is based on the recommendations of the Japanese health insurance regulations, which have not always been supported by clinical evidence.

Methods: The study subjects were 49 patients with CKD staged above 3 who had developed renal anemia requiring EPO. These patients were treated with EPO S. C. at the dose of 6,000 IU/week together with iron supplementation as deemed necessary for more than 24 weeks.

Results: The hemoglobin (Hb) value was 9.2 +/- 1.0 g/dL at the start, 10.9 +/- 1.6 g/dL at the peak (n = 49, p < 0.001 the start vs. the peak), and 9.0 +/- 1.6 g/dL at the commencement of dialysis (n = 49, p < 0.001 the peak vs. the commencement of dialysis). Seventy-one percent (35/49) of the patients achieved Hb levels over 10 g/dL, and 51% (25/49) achieved Hb levels over 11 g/dL. Conversely, 28% (14/49) of the patients failed to reach an Hb level over 10 g/dL. Factors explaining the good response to EPO (good responders were defined as those achieving Hb levels over 11 g/dL) had shown high Hb levels at the start (Logistic multiple regression analysis, p = 0.03) along with low creatinine concentration at the start (Cox's proportional hazard models, p = 0.015). Transferrin saturation (TSAT) at the start was 33.6 +/- 13.6%, 34.0 +/- 19.9% at the peak, and 24.7 +/- 11.6% at the commencement of dialysis, showing a significant reduction in TSAT at the commencement of dialysis compared to that at the start (n = 49, p = 0.0383, the start vs. the commencement of dialysis). Serum ferritin concentration was 140.7 +/- 139.5 pg/mL at the start, 107.9 +/- 110.8 pg/mL at the peak, and 131.9 +/- 112.4 pg/mL at the commencement of dialysis, indicating an absence of significant differences among the three time points.

Conclusions: The current health insurance regulations in Japan seem to be inappropriate in that the permitted EPO dosage of 6,000 IU/week might not be sufficient to achieve the target Hb level of more than 11 g/dL in most patients with CKD. To more efficiently achieve renoprotection, both early and timely initiation of EPO and reconsideration of the recommended EPO dosage appear to be warranted.