Received February 10, 2009
Accepted on May 6, 2009

ORIGINAL ARTICLES

Inflammation in Renal Transplantation

Sadollah Abedini ^*1, Ingar Holme , Winfried März , Gisela Weihrauch , Bengt Fellström ^||, Alan Jardine ^¶, Edward Cole ^**, Bart Maes , Hans-Hellmut Neumayer , Carola Grønhagen-Riska , Patrice Ambühl ^||||, Hallvard Holdaas ^¶¶, and on behalf of the ALERT study group.

*Renal Section, Department of Medicine, Toensberg County Hospital, Toensberg, Norway; Department of Preventive Medicine and Centre for Clinical Research, Oslo University Hospital Ullevaal, Oslo, Norway; Synlab for Medizinisches Versorgungzentrum für Labordiagnostik Heidelberg, Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Graz, Austria; ||Department of Medical Science, Renal Unit, University Hospital, Uppsala, Sweden; ¶Department of Medicine and Therapeutics, Western Infirmary Hospital, Glasgow, United Kingdom; **University Health Network, University of Toronto, Ontario, Canada; Medical Department, Heilig Hartziekenhuis, Roeselare, Belgium; Universitätsklinikum Charité, Berlin, Germany; University Hospital, Helsinki, Finland; ||||University Hospital, Zürich, Switzerland; and ¶¶Department of Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway

¹ To whom correspondence should be addressed. E-mail: Sadollah.abedini{at}gmail.com.

	Abstract

Background and objectives: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial.

Design, setting, participants, & measurements: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated.

Results: The baseline IL-6 value was 2.9 ± 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 ± 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049).

Conclusions: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.