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Moore J, He X, Cockwell P, Little MA, Johnston A, Borrows R
Transplantation. 2008;86:564-570
The authors performed a prospective analysis of data on 3859 adult patients who had functioning renal transplants for a minimum of 6 months. Patients from 64 centers in the United Kingdom were recruited between 1995 and 1998, enrolled in an industry-sponsored pharmacovigilance study of long-term efficacy and safety, and followed prospectively for up to 7 years. All patients received cyclosporine microemulsion, were enrolled for a mean of 45.5 months following transplantation, and had a mean follow-up of 4.0 years. A total of 382 patients (9.9%) died and another 445 returned to dialysis, resulting in death-censored and uncensored graft failure rates of 11.5% and 21.4%, respectively. Major causes of death were cardiovascular (41%), malignancy-related (26.5%), and infectious (17%), whereas the major cause of graft loss was unspecified/chronic rejection/chronic allograft nephropathy (75%). Lower hemoglobin level was associated with increased all-cause mortality as well as increased death-censored graft loss by univariate analyses, but the effect on mortality disappeared in the multiple regression model. Variables showing an association with increased hemoglobin level included recipient age, serum albumin, body mass index, and estimated glomerular filtration rate, whereas female gender and increased urea concentration were associated with lower hemoglobin level. Because an independent association between lower hemoglobin level and mortality was not found, the authors concluded that lower hemoglobin level should be considered a surrogate marker for mortality rather than a direct etiologic factor in renal transplant recipients. Moreover, the findings of this study suggest that full correction of hemoglobin level to improve mortality in renal transplant recipients is not justified and should be reserved to improve symptoms in markedly anemic patients and to avoid blood transfusions. However, because lower hemoglobin level was associated with inferior graft survival rate, further study is warranted to elucidate the mechanism between anemia and allograft function.
Anemia following renal transplantation is common and has become an increasingly recognized complication that may impact mortality and graft loss. The pathogenesis of posttransplant anemia is multifactorial and is usually associated with impaired allograft function, resulting in inadequate erythropoietin synthesis. Other risk factors for anemia in transplant recipients include: female gender, older donor and recipient age, the presence of infection, iron deficiency, the use of mammalian target of rapamycin inhibitors such as sirolimus, the use of antimetabolites such as mycophenolate mofetil or azathioprine, the use of hypotensive agents such as angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and chronic blood loss due to unrelated causes. In addition to myelosuppression, immunosuppressive agents may induce erythropoietin resistance that exacerbates anemia. In patients with chronic kidney disease, anemia has been associated with congestive heart failure as well as left ventricular hypertrophy and coronary ischemia. In transplant recipients, it has been suggested that the presence of anemia may be associated not only with cardiovascular complications but, in addition, may be an indication of overimmunosuppression. Treatment options for posttransplant anemia include iron supplementation, the use of erythrocyte-stimulating agents, the administration of blood products, prevention of infection, and minimization of immunosuppression. The findings of the above study suggest that mere correction of hemoglobin level does not improve mortality in transplant recipients and that the presence of anemia may be an epiphenomenon with regard to patient survival. However, lower hemoglobin level was associated with reduced graft survival, which suggests that anemia may represent a generalized marker of outcome when assessing the overall effects of various immunologic and nonimmunologic risk factors in specific patients.
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