In kidney transplant recipients, targeting high hemoglobin (Hb) concentrations with erythropoiesis-stimulating agents (ESAs) may delay progression of chronic allograft nephropathy by more than 3 years compared with targeting lower Hb levels, according to new study findings published in Nephrology Dialysis Transplantation.

Investigators led by Makoto Tsujita, MD, of Nagoya Daini Red Cross Hospital, studied 127 Japanese transplant recipients (mean age 48; 50% male) with anemia randomly assigned to a high (12.5–13.5 g/dL) or low (10.5–11.5 g/dL) Hb target. By design, no patient had iron deficiency anemia, history of coronary artery disease or cardiovascular disease (CVD), or Hb levels less than 10 g/dL following ESA therapy. Every 4 to 6 weeks, patients received dose-adjusted darbepoetin alfa or epoetin beta pegol intravenously or subcutaneously.

The high Hb group reached Hb levels of 12.5–13.5 g/dL at 18 months. By 36 months, mean Hb was 12.8 g/dL in the high Hb group and 11.5 g/dL in the low Hb group.

Estimated glomerular filtration rate (eGFR) declined significantly more in the low Hb group (-5.1 mL/min/1.73 m2) than in the high Hb group (-1.0 mL/min/1.73 m2).

In the high Hb group, 1 patient experienced a pulmonary embolism/deep vein thrombosis, 1 returned to hemodialysis, and 3 developed de novo hypertension. Chronic active antibody-mediated rejection occurred in 3 and 2 patients in the high and low Hb groups, respectively.

According to Dr Tsujita and the team, correction of anemia to Hb levels of 12.5–13.5mg/dL with an ESA showing a longer half-life prevents progression of chronic allograft nephropathy in kidney transplant recipients, as long as blood pressure is appropriately controlled.

Their study findings contrast with results from previous studies, which found a greater likelioodof cardiovascular events among patients with chronic kidney disease who had high Hb levels after ESA therapy.

“Taking into consideration the undesirable results of the aforementioned studies regarding the efficacy and safety of anemia correction, we attempted to gradually increase the Hb values to the target Hb concentration range by adjusting the ESA dosage,” Dr Tsujita and the team explained. “Although the mean Hb levels reached the target range at 18 months after the initiation of this study, our goal was successfully achieved in the remaining 18 months. This may be one of the reasons why serious adverse events such as CVD did not occur in the present study.”

The authors cautioned that Japanese patients differ from European and American patients in parameters such as in body mass index, so their findings may not apply to those populations. They also acknowledged that medication regimens, such as immunosuppressive agents and antihypertensive drugs, varied between groups, which may have influenced results.

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Reference

Tsujita M, Kosugi T, Goto N, et al. The effect of maintaining high hemoglobin levels on long-term kidney function in kidney transplant recipients: a randomized controlled trial. Nephrol Dial Transplant 2018:1–8. DOI:10.1093/ndt/gfy365