Treating Post-Transplant Renal Anemia in Routine Clinical Practice

Patients may develop anemia following kidney transplant, yet there are no specific post-transplant guidelines for management of the condition. Current international guidelines call for treatment recommendations and goals similar to those for patients with anemia of chronic kidney disease not dependent on dialysis (NDD-CKD). However, the incidence of post-transplant anemia is higher than the incidence of patients with CKD-NDD at the same estimated glomerular filtration rate (eGFR). The pathophysiology of post-transplant anemia is similar to that of CKD-associated anemia, but early post-transplant anemia is associated with additional factors related to surgery, induction therapy, and infections. 

Researchers in the Spanish Society of Nephrology transplant working group (SENTRA) and the anemia working group (GAS) recommended a shared nationwide study in real-world clinical settings to address the need for guidelines specific to anemia in kidney transplant recipients. The TRANSNEMIA study is a joint initiative of the SENTRA and GAS. Results were reported by José Portolés, MD, and colleagues in the Clinical Kidney Journal. 

The retrospective, noninterventional, multicenter study included patients from eight university kidney transplant hospitals in Spain. The study objective was to examine treatment patterns of anemia and objectives achieved in post-transplant patients, as well as the degree of compliance with current clinical guidelines in a clinical practice setting without intervention. 

Data were obtained from electronic medical records, including demographics, cause of CKD, comorbidities (cancer, cardiovascular events, diabetes mellitus, and Charlson Comorbidity Index score), and kidney transplant characteristics (donor type, immunosuppressive therapy, actual serum creatinine, and eGFR). Data related to anemia management (laboratory values, previously prescribed treatments, and subsequent adjustments) were also included.  

Anemia was defined as hemoglobin (Hb) <13 g/dL in men and Hb <12 g/dL in women, or any Hb treatment according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The European Renal Association position statement, European Renal Best Practice (EBPG) adapted the KIDGO recommendation for erythropoietic-stimulating agent (ESA) treatment for the European population, suggesting that Hb levels between 10 and 12 g/dL be achieved and maintained, while setting the target individually according to patient comorbidities. Hb values >13 g/dL should not be intentionally sought during ESA therapy according to the EBPG. 

The study cohort included 297 kidney transplant recipients with anemia and a functioning graft. Mean age was 62.8 years, and 60% were male. The kidneys were primarily from cardiac death donors (31.1%) or brain death donors (61.6%). Median time since transplant was 2.5 years and eGFR was 37.3 mL/min/1.73 m². The patients were divided into two groups: (1) those with early post-transplant anemia (first 6 months following transplant), n=69 (23%); and (2) those with late post-transplant anemia (≥7 months following transplant), n=228 (77%). 

Of the two groups, the mean Hb was numerically lower in the early anemia group (1.3 vs 11.6 g/dL). The percentages of patients with Hb on target (10-12 g/dL) were similar in the two groups, and there were more patients with severe anemia (15.9% vs 8.8% Hb <10 g/dL) in the early anemia group. Patients in the early anemia group had received more blood transfusions in the previous four months (27.5% vs 4.8%), and presented with higher eGFR, ferritin, and transferrin saturation index (TSAT). The two groups were similar in distribution of absolute or relative iron deficiency. 

Of the 297 transplant recipients, 53.2% (n=158) were receiving treatment with ESAs. The majority were being treated with darbepoetin (79.7%, median dose 1.0 µg/kg/month) or epoetin α (19.6%, median dose 133.3 IU/kg/month). Of the patients not being treated with ESAs, 13 had Hb level <10 g/dL and six were prescribed ESAs following that lab result. 

Functional iron deficiency was observed in 10.4% of the overall cohort, and 8.1% had absolute iron deficiency; distribution was similar for early and late anemia. The prevalence of iron deficiency and functional iron deficiency was higher among patients receiving treatment with ESAs. Those in the early anemia subgroup presented more iron deficiency compared to those in the late anemia subgroup (15.0% vs 8.5%, respectively). 

A total of 110 patients on ESA treatment were not receiving iron supplementation. Of them, 44 had an indication to receive iron according to guidelines and 30 had absolute iron deficiency. 

According to the EBPG recommendation, most patients receiving treatment with ESAs (n=71/158) had optimal Hb control within the range of 10-12 g/dL. Hb increased to the range of 12-12.9 g/dL in 42 patients, and it was above the limit of 13 g/dL in 27 of the 158 patients.  

Of the subgroup receiving treatment with ESAs, only 39 surpassed the limit for ESA resistance index, indicating poor response. ESA resistance was more frequent among patients with early anemia compared to patients with late anemia (26.1% vs 9.2%). Factors associated with the highest risk of resistance were iron profile, early post-transplant anemia, and eGFR. 

The researchers cited as limitations to the study findings the lack of external validation and the inability to generalize the findings to other health systems or countries.  

Summarizing the study’s key findings, the authors wrote, “a majority of ESA prescriptions meet guidelines; Hb targets are personalized to fall between 12 and 13 g/dL; iron supplements remain underutilized; and iron deficiency emerges as the primary cause of hyporesponsiveness to ESAs.” 

The authors said the results highlight a need for improvement strategies, which may include organized dissemination of anemia guidelines, clinical pathways for IV iron administration in outpatient clinics, and assisted prescription tools and early identification of resistance to ESAs or inflammation. They also noted an urgent need for additional research on anemia in kidney transplant patients to help inform guidelines and care. 

Source: Clinical Kidney Journal