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Inflammation in Renal Transplantation

Sadollah Abedini^*, Ingar Holme, Winfried März, Gisela Weihrauch, Bengt Fellström^||, Alan Jardine^¶, Edward Cole^**, Bart Maes, Hans-Hellmut Neumayer, Carola Grønhagen-Riska, Patrice Ambühl^||||, Hallvard Holdaas^¶¶; 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

Correspondence: Sadollah Abedini, Toensberg County Hospital, Medical Department, Renal Section, Post Box 2168, 3103 Toensberg, Norway. Phone: +47-3334-2000; Fax: +47-3334-3993; E-mail: Sadollah.abedini{at}gmail.com

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.