The Impact of Hemoglobin Levels on Patient and Graft Survival in Renal Transplant Recipients Jason Moore, 1 Xiang He, 2 Paul Cockwell, 1 Mark A. Little, 1 Atholl Johnston, 2 and Richard Borrows 1,3 Background. It remains unclear whether low hemoglobin levels are associated with increased mortality or graft loss after renal transplantation. This study assessed the relationship of hemoglobin levels with patient and graft survival in 3859 patients with functioning renal transplants more than 6-months posttransplantation. Methods. Detailed data was prospectively collected as part of the pharmacovigilance Long Term Efficacy and Safety Surveillance project. Results. Lower hemoglobin levels were associated with graft loss on multivariate analysis adjusted for demographic characteristics, comorbidity, and biochemical variables; lower hemoglobin was associated with mortality on univariate, but not adjusted analysis; hemoglobin variability was associated with mortality and graft loss on univariate, but not multivariate analysis. Older recipient age, lower serum albumin, raised urea, increased comorbidity (Charlson Index), and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) non-use were also asso- ciated with mortality. Younger recipients, male recipients and those with lower serum albumin, lower body mass index, higher systolic blood pressure, and impaired allograft function experienced higher graft failure rates. Conclusions. This study suggests that full correction of hemoglobin levels to improve mortality in renal transplant recipients is unjustified; further study is required to assess the effect of hemoglobin correction in delaying graft failure. It also highlights other nonimmunologic risk factors for adverse outcomes in renal transplant recipients. Keywords: Kidney transplantation, Anemia, Hemoglobin. (Transplantation 2008;86: 564–570) A nemia after renal transplantation remains a common finding (1). Risk factors for the development of anemia have been well defined (1–7), but it is less clear whether post- transplantation anemia is associated with adverse recipient outcomes. Although some studies suggest anemia is associ- ated with increased mortality in renal transplant recipients (2, 3, 8, 9), other studies argue to the contrary (10, 11). Limitations of published data include lack of control- ling for confounding variables, in particular immunosup- pressive regimen, comorbidity, concurrent biochemical parameters, immunologic determinants of transplant out- come, cardiovascular risk factors, and inflammation. Analyz- ing hemoglobin values as a continuous variable (rather than as a dichotomous variable) may lead to greater insight as to the presence (or absence) of a hemoglobin “threshold” in determining outcomes (12). The relationship between he- moglobin variability and outcomes has not been studied in transplant recipients. In addition, although registry data has shown associations between anemia and congestive heart fail- ure (13, 14), studies of mortality as an end-measure are largely limited to single center reports (2, 3, 8 –11). Larger studies, controlling adequately for potential confounders, are clearly necessary. We addressed these limitations by interrogating the Long Term Efficacy and Safety Surveillance (LOTESS) da- tabase, a registry dataset which has yielded valuable insight into renal transplant outcomes in previous analyses (15–17). Although not as large as North American datasets, the data- base benefits from detailed laboratory, demographic and clinical data collection from a representative United King- dom (UK) cohort. It has also allowed the assessment of the impact on long-term outcomes for various immunologic and nonimmunologic risk factors, beyond the initial pe- riod posttransplantation. MATERIALS AND METHODS Patient Population The LOTESS database is a Novartis funded pharmaco- vigilance project which collected data on renal transplant re- cipients treated with microemulsion ciclosporin (Neoral) therapy. LOTESS is an open, observational cohort study and is conducted according to the guidelines for the safety assess- ment of marketed medicines (18). Participating centers sub- mitted data on a three monthly basis to the central medical information processing and statistics department; data were collected by trained professional study monitors operating to good clinical practice standards; information was verified and anonymised. Patients from 64 centers in the UK were recruited be- tween 1995 and 1998, and followed prospectively for up to 7 years. Information collected was checked against the patients’ original clinical records. Although the database is limited to patients treated with microemulsion ciclosporin, the use of alternative calcineurin inhibitors (i.e., tacrolimus) was un- common in the UK during the period of data collection, and therefore is largely representative of the UK renal transplant population as a whole. Data were analyzed for adult (age 18 years) renal transplant recipients surviving with a functioning JM and XH have received unrestricted educational grants from Novartis. 1 Department of Nephrology and Renal Transplantation, University Hospi- tal Birmingham, Edgbaston, Birmingham B15 2TH, United Kingdom. 2 Department of Clinical Pharmacology, Barts and The London School of Medicine and Dentistry, London EC1M 6BQ, United Kingdom. 3 Address Correspondence to: Dr. R. Borrows, M.A., M.R.C.P., Department of Nephrology and Renal Transplantation, University Hospital Birming- ham, Edgbaston, Birmingham B15 2TH, United Kingdom. E-mail: richard.borrows@uhb.nhs.uk Received 27 February 2008. Revision requested 20 March 2008. Accepted 9 May 2008. Copyright © 2008 by Lippincott Williams & Wilkins ISSN 0041-1337/08/8604-564 DOI: 10.1097/TP.0b013e318181e276 564 Transplantation • Volume 86, Number 4, August 27, 2008