Clinical Trial Summary
RBC transfusion (RBCT) after kidney transplantation(KT) is about 50%. Anemia is common after
kidney transplant surgery due to intraoperative blood loss, delayed graft function, and side
effects of immunosuppressive drugs. However, due to exposure to non-self human leukocyte
antigens (HLA) from blood transfusion, there is a risk of sensitization to HLA through the
production of anti-HLA antibodies. In renal transplant patients, exposure to non-self HLA
antigens due to RBCT can lead to the generation of donor-specific antibodies (DSA) against
renal allograft donors. Patients who have undergone KT are frequently exposed to RBCT, and
immunologic damage resulting from this can be an important cause of loss of graft kidney
function. Therefore, there should be a more careful review of the risk associated with RBCT
on KT recipients.
Of the 16,191 Koreans who underwent KT between 2008 and 2017, 59.7% received
transplant-related blood transfusions. As a result of analyzing 13,871 Koreans who underwent
KT between 2007 and 2015, the overall graft failure rate was 15.5%, and the hazard ratio of
survival rate according to RBCT before and after KT increased as the amount of transfusion
increased. RBCT before and after KT was independently associated with graft failure and
death. Therefore, research on treatment methods that can effectively reduce blood transfusion
in transplant patients is absolutely necessary. About 30-60% of patients undergoing major
surgery show preoperative anemia, which causes blood transfusions, complications during
hospitalization, prolonged hospitalization, and delayed recovery. The most common cause of
anemia is iron deficiency. In particular, an increase in hepcidin, a major regulator of iron
metabolism, reduces intestinal iron absorption and promotes iron sequestering by macrophages,
resulting in a state of functional iron deficiency. Therefore, oral iron intake as a
treatment for anemia in surgical patients is not effective. Although the safety and clinical
superiority of high-dose intravenous iron therapy have been demonstrated in patients with
chronic renal failure, the effect of this drug on blood transfusion of pre- and post-kidney
transplant surgery has not been studied. Therefore, this study aims to verify the
effectiveness and stability of the combined administration of intravenous(IV) iron and
erythropoiesis-stimulating agents(ESA) before and after KT for patients who perform KT for
end-stage kidney disease(ESKD). The investigators will analyze hemoglobin, transferrin
saturation, ferritin changes, and transfusion requirements according to the combined
administration of IV iron and ESA before and after surgery of kidney transplant patients.
Also, the investigators evaluate whether a treatment combining IV iron and ESA will be
possible as an alternative blood transfusion treatment and its effect on the clinical
prognosis of KT recipients. In particular, the effect on the function of the graft kidney,
immunological outcomes-DSA, antibody-mediated rejection, and survival rate will be analyzed.
Also, the investigators will analyze the change in expression of hepcidin and oxidative
stress markers before and after kidney transplantation and the mechanism of expression
according to the combined administration of IV iron and ESA. This study is a
multicenter(including 3 centers), open-label, prospective, and randomized clinical trial. 302
patients undergoing living-donor KT for ESKD are randomly assigned in a 1:1 ratio to an
experimental group actively using IV iron and ESA, and a control group receiving conventional
anemia treatment for 42 months from the time of IRB approval. Participants selected for the
experimental group will be given a total of 1000 mg of IV Monofer(iron isomaltoside); each
200 mg dose on 28, 21, and 7 days before kidney transplantation, on the day of surgery, and 7
days after surgery. In the case of ESA, it is freely used according to the criteria up to 7
days before transplantation and subcutaneously injected with 120 mcg of Mircera(methoxy
polyethylene glycol-epoetin beta) between 7 days before surgery and a day before surgery. In
the control group, IV Monofer is administered only 28 days before surgery according to the
set criteria. Mircera is also freely used in the control group according to the criteria up
to 7 days before KT but not used between 7 days before surgery and a day before surgery.
Total 302 subjects, Experimental group vs Control group, 1. Experimental group :
- Total of 1000 mg Monofer(iron isomaltoside) IV injection; each Monofer 200mg dose on
①28, ②21, and ③7 days before KT,
- on the day of surgery, and ⑤7 days after surgery
- Mircera(methoxy polyethylene glycol-epoetin beta) 120mcg SQ once : between 7 days before
surgery and a day before surgery.
* In the case of ESA, it is freely used according to the criteria up to 7 days before
transplantation
2. Control group :at 28 days before KT, Monofer is administered according the following
criteria.
- Ferritin <100 μg/L & TSAT<20% : Monofer 200mg IV, twice
- Ferritin 100~200 μg/L & TSAT<20% : Monofer 200mg IV, once
- Ferritin 201~500 μg/L & TSAT<20% : Monofer 100mg IV, once
- Not administer in other cases * In the case of ESA, it is freely used according to the
criteria up to 7 days before transplantation
