A new insight into the treatment of renal anemia with HIF stabilizer
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(2020) 6:63
REVIEW
Open Access
A new insight into the treatment of renal anemia with HIF stabilizer Satoru Kuriyama1,2*, Yukio Maruyama3 and Hirokazu Honda4
Abstract The long-term clinical experiences with recombinant human erythropoietin (rHuEPO) and its analog derivatives have clearly proven that correction of anemia with erythropoiesis stimulating agent (ESA) not only reduces blood transfusion and improves patients’ QOL but has multiple benefits for the concurrent complications of CKD such as Cardio-Renal–Anemia (CRA) syndrome and/or malnutrition-inflammation-atherosclerosis (MIA) syndrome. Unlike ESA, the newly available agent, hypoxia-inducible factor (HIF) stabilizer, stimulates endogenous erythropoietin (EPO) by mimicking hypoxia with HIF prolyl hydroxylase domain enzyme (HIF-PHD) inhibition. The phase 2 and 3 clinical studies have shown that HIF stabilizers are as efficacious as ESA in ameliorating renal anemia. Whether the same clinical benefits on CRA and MIA syndrome hold true in patients given HIF stabilizers is a matter for future debate. Given that HIF stabilizers act on the multiple target genes, the use of this novel agent may lead to unwanted adverse events. Launching HIF stabilizers into the treatment of renal anemia provokes a concern about how this alternative treatment will be taken up in the daily clinical practice. However, guideline-oriented strategies on how to use HIF stabilizer is not available at this limited point due to scant clinical information. Nevertheless, this opinion-based review provides a future insight into the management of renal anemia with HIF stabilizer by reference to the past experiences with ESA. HIF stabilizers can preferably be indicated for CRA syndrome at pre-dialysis stage, ESA resistant anemia at advanced CKD stage, and perhaps for dysregulated iron metabolism akin to MIA syndrome in patients on dialysis. Keywords: Hypoxia inducible factor (HIF) stabilizer, Hypoxia, Erythropoiesis stimulating agent (ESA), CRA syndrome, MIA syndrome, Iron metabolism
Introduction The epoch-making recombinant human erythropoietin (rHuEPO) came into clinical practice for renal anemia in chronic kidney disease (CKD) patients on dialysis in 1990, and its indication was extended to those at predialysis stage in 1994 in Japan. The pharmacological potency of correction of anemia with rHuEPO and its pharmacological analogues was so efficacious that most * Correspondence: [email protected] 1 Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan 2 Nephrology & Hypertension Research Unit, Internal Medicine, Miho Clinic, Shin-Osaki-kangyo Bld 2F, Osaki, Shinagawa-ku, Tokyo 141-0032, Japan Full list of author information is available at the end of the article
of the CKD patients benefited from the treatment. One of the remarkable effects of the erythropoiesis stimulating agents (ESA) was the reduction in blood transfusion that contributed to the prevention of blood-transfusion-borne infections such as viral hepatitis and other intractable li
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