Kidney transplant recipients re-entering hemodialysis (HD) with a failing allograft are frequently more anemic than are patients just starting HD. Chronic rejection can lead to a more anemic, catabolic and inflammatory state in patients re-entering hemodialysis.

In a new study, Japanese researchers hoped to clarify how focusing on the control of anemia with the use of erythropoiesis stimulating agents can help transplant recipients re-enter dialysis safely.

Ken Sakai, M.D., Ph.D., and a team of researchers from Toho University in Tokyo, Japan, compared the charts of 30 patients with chronic kidney disease (CKD) and 29 transplant recipients starting hemodialysis at that institution in 2012 through 2014. The chronic kidney disease with transplant (CKDT) group re-entered HD after chronic rejection.

Compared with the patients with CKD, transplant patients were younger, with an average age of 42 years versus 53 years. Transplant patients were less likely to have diabetes; 10 percent of the transplant recipients had diabetes versus 36 percent of those with chronic kidney disease. The CKDT group had a mean graft survival of 12.5 years.

The researchers compared test results and hospital stays between CKD and CKDT groups at entering dialysis, and the results were similar in many cases. The researchers found no differences in cardiothoracic ratio, GFR and initial ultrafiltration. Hemoglobin concentration was also similar between CKD and CKDT groups at approximately 9 g/dL.

None of the patients received blood transfusion. Comparable C-reactive protein and albumin values suggest inflammation and nutritional status was alike between the groups. Duration of hospitalization during the initiation of dialysis was also similar, "suggesting an absence of complications on entry to dialysis in both groups," according to the researchers.

Mean weight at entry to dialysis was the only difference between the CKD and CKDT groups, with a 58.5 mean weight for the CKDT group and 67.1 kg for the CKD group. The darbepoetin dose per kilogram of weight were similar between the groups, at 2.28 ± 2.03 μg/kg for the CKDT group and 2.12 ± 1.6 μg/kg for the CKD group, in the month before their entry into hemodialysis.

Renal function declined similarly between the two groups in the months leading up to hemodialysis, with eGFR 5.97 mL/min/1.73 m2 for CKDT patients and 5.58 mL/min/1.73 m2 for the chronic kidney disease patients.

Previous research by Yves Vanrenterghem and colleagues found limited use of erythropoietin-stimulating agents (ESAs) and continuation of immunosuppressive therapies among transplant patients initiating hemodialysis. Only 17.8 percent of transplant recipients with severe anemia received the ESA epoetin and, according to the researchers in the most recent study, this practice could result in anemia in more patients.

Epoetin and other ESAs treat lower than normal red blood cells (RBCs) caused by chronic kidney disease. Epoetin is an injectable drug that stimulates the production of RBCs in bone marrow.

A variety of factors could contribute to anemia occurring more than six months after transplantation and should be ruled out before the administration of ESA. Attending physicians should rule out graft dysfunction, immunosuppression, rejection, infection, antihypertensive medication, hemolysis, iron deficiency and malignancy.

The researchers acknowledged study limitations, such as a small study group and wide age difference.

Graft survival is not always enough, even with a living, related transplantation. In cases of chronic rejection, safe reinitiation is essential for recipient survival.

Immunosuppression and rejection can cause anemia. This new research suggests, however, that adequate administration of ESA could level the playing field between CKD and CKDT recipients.