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

doi:10.1136/bmj.b4018

Published 23 October 2009, doi:10.1136/bmj.b4018
Cite this as: BMJ 2009;339:b4018

Research

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

Georg Heinze, research scientist¹, Alexander Kainz, research scientist², Walter H Hörl, professor and head of department², Rainer Oberbauer, professor, head of department²^,3^,4

¹ Core Unit of Medical Statistics and Informatics, Medical University of Vienna, 1090 Vienna, Austria, ² Department of Nephrology, Medical University of Vienna, 1090 Vienna, Austria, ³ Austrian Dialysis and Transplant Registry, 4010 Linz, Austria, ⁴ Department of Nephrology, KH Elisabethinen, 4010 Linz, Austria

Correspondence to: R Oberbauer, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria rainer.oberbauer{at}meduniwien.ac.at

Objective To determine the optimal range of increase in haemoglobinconcentration with treatment with erythropoietins that is safeand is not associated with mortality.

Design Retrospective cohort study. The analysis was adjustedfor several covariables with Cox regression analysis with splinefunctions. Use of erythropoietins, haemoglobin concentration,and covariables were included in a time varying manner; variableselection was based on the purposeful selection algorithm.

Setting Transplantation centres in Austria.

Participants 1794 renal transplant recipients recorded in theAustrian Dialysis and Transplant Registry who received a transplantbetween 1 January 1992 and 31 December 2004 and survived atleast three months.

Main outcome measures Survival time and haemoglobin concentrationafter treatment with erythropoietins.

Results The prevalence of use of erythropoietins has increasedover the past 15 years to 25%. Unadjusted extended Kaplan-Meieranalysis suggests higher mortality in patients treated witherythropoietins, in whom 10 year survival was 57% compared with78% 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, haemoglobinconcentrations >125 g/l were associated with increased mortalityin treated patients (hazard ratio 2.8 (95% confidence interval1.0 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 haemoglobinconcentrations were 147 g/l or above, patients treated witherythropoietins showed significantly higher mortality than thosewho were not treated (3.0, 1.0 to 9.4).

Conclusion Increasing haemoglobin concentrations to above 125g/l with erythropoietins in renal transplant recipients is associatedwith an increase in mortality. This increase was significantat concentrations above 140 g/l.

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