Research Highlight | 13 November 2020

Reassessing targets for managing kidney disease

Trial suggests doctors in Japan may be overtreating anemia in patients with non-diabetic kidney failure

Suggestions have emerged for better managing hemoglobin levels in people with renal anemia in Japan based on a new trial overseen by members of the Translational Research Center for Medical Innovation1.

Drugs that stimulate the production of iron-containing red cells in the blood have greatly improved the care of people with chronic kidney disease. Yet despite the use of these agents in clinical settings for more than 30 years, it is still unclear what therapeutic strategy is ideal for offsetting the threat of renal anemia without elevating the risk of heart attack, stroke and other cardiovascular complications.

Current guidelines from the leading medical societies in Japan, which are based on small studies conducted nationally, advise doctors to aim to boost levels of hemoglobin — an iron-carrying component of red blood cells — to a relatively high level.

To investigate whether this is the optimal strategy, Enyu Imai, director of the Nakayamadera Imai Clinic in Takarazuka and his colleagues conducted a randomized trial on almost 500 patients with non-diabetic kidney disease (mean age of 70). Each participant received darbepoetin alfa, a long-acting analogue of a kidney hormone called erythropoietin, which is critical for the production of red blood cells. Half the patients were randomly assigned to a high target hemoglobin level and half to a low target.

The researchers tracked the study participants for up to two years, managing their anemia within the target window. By the end of the study, they observed a 22% reduction of the primary kidney composite end point in the high-hemoglobin group, but this was not statistically significant. The incidence of cardiovascular composite endpoint was low in both groups and no statistically significance difference was seen between them.

“Our data indicate that the uppermost levels recommended could be potentially overtreatment, offering little benefit, especially for patients over 70 years old,” Imai says “In the light of our findings, I feel that Japan’s medical societies should reconsider the target hemoglobin level in non-dialysis patients undergoing treatment for renal anemia with erythropoiesis-stimulating agents.”

To Imai, the results show that the best option for patients with non-diabetic chronic kidney disease may be to aim for intermediate levels. This strategy would help strike the right therapeutic balance — both preserving kidney function and avoiding cardiovascular disease. It would also help align medical practice in Japan with how renal anemia is handled in the rest of the world.


  1. Hayashi, T., Maruyama, S., Nangaku, M., Narita, I., Hirakata, H. et al. Darbepoetin alfa in patients with advanced CKD without diabetes: Randomized, controlled trial. Clinical Journal of the American Society of Nephrology 15, 608–615 (2020).| article

About the Researcher

Enyu Imai, Director of Nakayamadera Imai Clinic

Dr. Enyu Imai is a director of Nakayamadera Imai Clinic and Visiting Professor of Nephrology, Fujita University School of Medicine and Aichi Medical College. He and his colleagues developed an equation for estimating the glomerular filtration rate from serum creatinine and estimated the chronic kidney disease population in Japan. He has published more than 300 scientific papers in English. He has served on the editorial boards of Nature Review Nephrology, Journal of the American Society of Nephrology and Kidney International, as subject editor of Nephrology Dialysis Transplantation and as associate editor of the American Journal of Kidney Disease.

Fujita Health University

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