Introduction: Posttransplant anemia (PTA) is a common complication of kidney transplant recipients. Previous reports demonstrated that PTA could be associated with reduced(increased?) mortality, reduced graft survival, and decline in glomerular filtration rate. Erythropoiesis-stimulating agents (ESAs) are used for the treatment of late PTA to achieve better graft survival. Hyporesponsiveness to ESAs in patients with chronic kidney disease (CKD) is a predictor for poor renal and cardiovascular outcome. Previously, up to 10% of patients with CKD showed poor responsiveness to ESAs. However, a method to measure ESA hyporesponsiveness has not yet been established. Moreover, there are few reports regarding hyporesponsiveness to ESAs in kidney transplant recipients with PTA. In this present study, we analyzed the prevalence of ESA hyporesponsiveness in kidney transplant recipients with PTA.
Methods: A cross-sectional observational study was conducted to investigate the prevalence of ESA hyporesponsiveness in kidney transplant recipients with late PTA at Osaka Metropolitan University Hospital. A total of 249 patients who were followed at least a year after living or deceased kidney transplantation between April 2020 to July 2020 were enrolled in this study. PTA was defined as hemoglobin level <11 g/dl or receiving an ESA. ESA hyporesponsiveness was defined as kidney transplant recipients requiring >6000 units/week of rHuEPO or requiring 0.75 μg/kg/2 weeks of darbepoetin alfa (DA) to maintain the target Hb (Hb>11 g/dl). ESA doses of epoetin beta pegol (CERA) and DA were multiplied by 200 to be converted to rHuEPO doses, and ESA doses of CERA and DA were considered equal.
Results: A total of 60 out of the 249 recipients had late PTA including 28 male and 32 female patients. Fifty-six of these patients received an ESA (CERA or DA). According to the criteria of hyporesponsiveness, which was kidney transplant recipients requiring >6000 units/week of rHuEPO, ESA hyporesponsiveness was diagnosed in 16.1% of patients with late PTA. Using the criteria of ESA hyporesponsiveness which was recipients requiring 0.75 μg/kg/2 weeks of DA, it was diagnosed in 46.4% of patients with late PTA.
Discussion: Although the prevalence of ESA hyporesponsiveness in kidney transplant recipients differed according to the criteria used in this present study, the prevalence of hyporesponsiveness to ESA may be higher in kidney transplant recipients than in non-dialysis CKD patients. Hyporesponsiveness to ESAs may be involved in the pathophysiology of PTA, possibly relating to risk factors such as iron deficiency, infections, and myelotoxic drugs.