Up to 30% of kidney transplant recipients suffer from anemia at some point after transplantation, and it has been proposed that this can contribute to adverse cardiovascular events. Studies have shown that during the early postoperative period, anemia is caused by blood loss, graft failure, or erythropoiesis-inhibiting drugs, whereas late post-transplantation anemia (PTA) is caused by renal dysfunction, immunosuppressive drugs, or infection. In addition, it has been shown that anemia at baseline significantly predicts mortality and graft failure in these patients. Despite this research, extensive studies on PTA have not been published. Therefore, a recent retrospective study was undertaken to examine the impact of PTA on patient and graft survival, and the rate of acute graft rejection.

This study by Chhabra et al included 1,023 patients who underwent kidney transplantation at a single center. Of these patients, 13% were found to be anemic by the study’s hemoglobin (Hb) level definition (Hb < 11 g/dL). Based on multivariate models that considered gender, race, pre-transplant Hb level, donor age, and infections after transplant as variables, the study assessed the independent association of anemia and negative outcomes. At 90 days post-transplantation, the presence of anemia was significantly and independently associated with increased overall mortality, as well as increased rejection rates. In addition, Kaplan-Meier curves for graft survival and rate of rejection were significantly worse in anemic patients compared to nonanemic patients.

The results of this study suggest a greater likelihood of negative outcomes in patients with PTA, and the authors suggest some of the possible mechanisms of this association. Because anemia can contribute to cardiovascular disease such as left ventriclular hypertrophy and congestive heart failure, it is plausible that PTA could be a similar predictor of cardiovascular morbidity. In addition, the limited oxygen delivery to tissues when anemia is present could be a key reason for poorer graft survival rates. The pathogenesis of the temporal association between PTA and rate of rejection is more difficult to understand, but statistical significance remains even after adjustment for different post-transplant periods. Although this study was limited by retrospective analysis and a lack of patient family history, the findings are consistent with other related research and need to be further explored.

Impact of anemia after renal transplantation on patient and graft survival and on rate of acute rejection. Chhabra D, Grafals M, Skaro AI, Parker M, Gallon L. Clin J Am Soc Nephrol. 2008 Jul;3(4):1168-74.

NAAC Expert Commentary:
Anemia is a common feature in patients following kidney transplantation. The pathogenesis is multifactorial, with residual chronic kidney disease, blood loss, and the effects of immunosuppressive drugs likely contributing. It has been hypothesized that the morbid impact of anemia in transplant patients is similar to that in patients with CKD or those on dialysis. That is, that anemia patients would be more likely to have cardiovascular disease, higher hospitalization rates, and poorer survival. This study confirms the high frequency of anemia in this population and does highlight some of the associated poorer outcomes, as predicted. In addition, poorer graft survival is noted in the anemic patients as well as an increased rate of graft rejection.

Because this is a retrospective study, however, it is difficult to determine mechanisms of these associations. For example, is anemia causing these adverse outcomes or merely a marker of patients who are likely to have poorer outcomes? Only prosepective trials will be able to answer this question. Of equal importance is the issue of treatment of anemia and its impact on outcomes. With the availability of ESAs, treatment is not complex. Studies to determine if such treatment will result in better outcomes are sorely needed.

Last Modified: August 14, 2008