Iron Therapy Underutilized in Post-Kidney Transplant Anemia, Study Finds

Marta Crespo, MD, PhD

Credit: LinkedIn

A new investigation into current management for post-kidney transplant anemia revealed the use of erythropoietic-stimulating agents (ESAs) met guideline recommendations, while iron supplementation continued to be underutilized, even in patients who could benefit from a reduction in ESA dose.¹

This retrospective, multicenter study sought to examine the state of anemia management, goals, and adherence to guidelines within a representative sample of the kidney transplant population involving outpatients from 8 university hospitals in Spain.

“These findings highlight the need for improvement strategies, such as structured dissemination of anemia guidelines, development of clinical pathways to intravenous (IV) iron administration in outpatient transplant clinicians, assisted prescription tools, and early identification of resistance to ESAs or inflammation,” wrote the investigative team, led by Marta Crespo, department of nephrology, Hospital del Mar.

Post-transplant anemia is a relevant clinical issue, yet is often overlooked by transplant nephrologists, compared with graft survival, rejection, or infection.² There are no specific post-transplant anemia guidelines—instead, guidelines consider the same treatment recommendations and goals as patients with anemia and non-dialysis-dependent chronic kidney disease (NDD-CKD).³

However, the incidence of post-transplant anemia is higher than in patients with NDD-CKD, with some differences in relevant factors, including inadequate erythropoietin (EPO) production and iron deficiency. Given the lack of general awareness of post-transplant anemia, despite its notable clinical implications, Crespo and colleagues sought to provide a comprehensive assessment of current management strategies and opportunities for improvement.¹

The TRANSNEMIA study was a joint initiative of the transplant-working group (SENTRA) and the anemia-working group (GAS) of the Spanish Society of Nephrology. Adults with a functioning graft and anemia classified as early post-transplant anemia (≤6 months) were included for analysis.

At baseline, the team of nephrologists retrieved electronic medical record (EMR) data on demographics, comorbidities, cause of CKD, primary data on kidney transplant, anemia treatments, and laboratory values. The team also collected information on transfusions, hospital admissions, and prescriptions of ESAs and iron during the previous 4 months.

KDIGO guidelines defined anemia as hemoglobin (Hb) levels <13 g/dL in men and Hb <12 g/dL in women, or any Hb levels with ESA treatment. An indication for iron therapy was defined according to the European Renal Best Practice (EPBG) position statement, recommending a trial of IV iron or a 3-month oral trial.

The TRANSNEMIA analysis included 297 patients with anemia and a functioning graft, of whom 60% were male and the mean age was 62.8 years. This population had primarily received a graft from cardiac death (61.6%) or brain death (31.1%) donors a median of 2.5 years earlier.

Among the population, 228 (77%) were classified as having late post-transplant anemia and 69 (23%) had early anemia. Those with early anemia exhibited a numerically lower mean Hb (11.3 vs. 11.6 g/dL), the same percentage of patients with on-target Hb (10–12 g/dL), and more with severe anemia (Hb <10 g/dL: 15.9% vs. 8.8%).

Meanwhile, 158 (53.2%) patients were treated with ESAs and exhibited a higher absolute and functional iron deficiency prevalence. Individuals with early anemia showed higher iron deficiency rates than those with late anemia (15.0% vs. 8.5%).

Notably, nearly three-quarters (72.4%) of those treated with ESAs did not receive iron supplementation. However, guideline-directed definitions showed 44 patients had an indication to receive iron supplementation, as 30 patients met the criteria for absolute iron deficiency.

Crespo and colleagues noted these findings were worse for those with late anemia on ESAs, as 28% demonstrated absolute iron deficiency, and 43.9% were indicated for an iron prescription, but no patient received supplementation

Among the full population receiving ESAs, only 39 surpassed the limit for the ESA resistance index (ERI) (12.7 IU/kg/week), suggesting a poor response. Resistance to ESA was more frequent during the early period (26.1 vs. 9.2%; P <.001). Iron profiles, early post-transplant anemia, and eGFR rates were the primary factors of the highest ERI tertile.

“There is a pressing need for dedicated studies focused on anemia in kidney transplant patients,” Crespo and colleagues wrote. “These studies are essential for generating reliable evidence that can inform personalized prescriptions and treatment objectives as specific post-transplant anemia guidelines.”

References

1. _{Portoles J, Crespo M, Martínez Belotto M, et al. Post-transplant renal anemia: a call to action from a national study in routine clinical practice. Clin Kidney J. 2024;17(10):sfae269. Published 2024 Aug 30. doi:10.1093/ckj/sfae269}
2. _{Winkelmayer WC, Chandraker A. Pottransplantation anemia: management and rationale. Clin J Am Soc Nephrol. 2008;3 Suppl 2(Suppl 2):S49-S55. doi:10.2215/CJN.03290807}
3. _{Locatelli F, Bárány P, Covic A, et al. Kidney Disease: Improving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement. Nephrol Dial Transplant. 2013;28(6):1346-1359. doi:10.1093/ndt/gft033}