Mortality in renal transplant recipients given erythropoietins to increase haemoglobin concentration: cohort study

OBJECTIVE To determine the optimal range of increase in haemoglobin concentration with treatment with erythropoietins that is safe and is not associated with mortality. DESIGN Retrospective cohort study. The analysis was adjusted for several covariables with Cox regression analysis with spline functions. Use of erythropoietins, haemoglobin concentration, and covariables were included in a time varying manner; variable selection was based on the purposeful selection algorithm. SETTING Transplantation centres in Austria. PARTICIPANTS 1794 renal transplant recipients recorded in the Austrian Dialysis and Transplant Registry who received a transplant between 1 January 1992 and 31 December 2004 and survived at least three months. MAIN OUTCOME MEASURES Survival time and haemoglobin concentration after treatment with erythropoietins. RESULTS The prevalence of use of erythropoietins has increased over the past 15 years to 25%. Unadjusted extended Kaplan-Meier analysis suggests higher mortality in patients treated with erythropoietins, in whom 10 year survival was 57% compared with 78% in those not treated with erythropoietins (P<0.001). In the treated patients there were 5.4 events/100 person years, compared with 2.6 events/100 person years in those not treated (P<0.001). After adjustment for confounding by indication, comorbidities, comedication, and laboratory readings, haemoglobin concentrations >125 g/l were associated with increased mortality in treated patients (hazard ratio 2.8 (95% confidence interval 1.0 to 7.9) for haemoglobin concentration 140 g/l v 125 g/l), but not in those not treated (0.7, 0.4 to 1.5). When haemoglobin concentrations were 147 g/l or above, patients treated with erythropoietins showed significantly higher mortality than those who were not treated (3.0, 1.0 to 9.4). CONCLUSION Increasing haemoglobin concentrations to above 125 g/l with erythropoietins in renal transplant recipients is associated with an increase in mortality. This increase was significant at concentrations above 140 g/l.