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Larry A Weinrauch,1–4 Brian Claggett,1,4 Jiankang Liu,1 Peter V Finn,1 Matthew R Weir,5 Daniel E Weiner,6 John A D’Elia2–4 1Cardiovascular Division, Brigham and Women’s Hospital, 2Kidney and Hypertension Section, Joslin Diabetes Center, 3Department of Medicine, Beth Israel Deaconess Hospital, 4Harvard Medical School, Boston, MA, 5Division of Nephrology, Department of Medicine, University of Maryland, College Park, MD, 6Division of Nephrology, Tufts University School of Medicine, Boston, MA, USA Background: Tobacco use remains an international health problem with between 10% and 40% of adults currently using tobacco. Given the rising number of patients either awaiting or having received a kidney transplant and the absence of smoking cessation as the criterion for transplantation in guidelines, we explored the association between smoking status and clinical outcomes in kidney transplant recipients. Patients and methods: In this post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplant trial, the associations between smoking status, defined as never having smoked, formerly or currently smoking, and both all-cause mortality and graft survival were assessed using Cox proportional hazards models. Fatal events were centrally adjudicated into prespecified categories: all-cause, cardiovascular and non-cardiovascular causes. Graft loss was defined as return to dialysis or retransplantation. Clinical Trials URL: http://www.clinicaltrials.gov/show/NCT00064753. Results: Among 4110 transplant recipients, there were 451 current smokers and 1611 former smokers. The mortality rate per 100 patient-years was 4.0 (71 deaths) for smokers, 3.5 (226 deaths) for former smokers and 2.4 (116 deaths) for never smokers. Hazard ratio for mortality for current smokers was 1.70 (CI=1.26–2.29, p=0.001) and for former smokers was 1.21 (0.98–1.50, p=0.08) with 1.0 representing never smokers. As the number of cardiovascular deaths was similar in each group (all p>0.3), the differences between groups was driven by non-cardiovascular death rates. Current smokers (2.39; 1.62–3.61, p100% increased risk of non-cardiovascular death, 70% greater risk of all-cause mortality and a 50% greater risk of graft loss, a risk not seen in former smokers. These findings confirm previous non-adjudicated observations that smoking is associated with adverse clinical outcomes and suggest that more emphasis should be placed on smoking cessation prior to kidney transplantation. Keywords: tobacco, infection, infectious death, transplant loss, graft loss, non-cardiovascular mortality, diabetes&nbsp

Larry A Weinrauch,1–4 Jiankang Liu,1 Brian Claggett,1 Peter V Finn,1 Matthew R Weir,5 John A D’Elia2–4 1Cardiovascular Division, Brigham and Women’s Hospital, 2Kidney and Hypertension Section, Joslin Diabetes Center, 3Department of Medicine, Beth Israel Deaconess Hospital, 4Harvard Medical School, Boston, MA, 5Division of Nephrology, Department of Medicine, University of Maryland, Baltimore, MD, USA Introduction: Single-center and observational studies have suggested that calcium channel blocking agents may decrease the expression of sepsis in individual populations. In the renal transplant population, a role for calcium channel blockers in allograft protection and in prevention of sepsis has been postulated. We hypothesized that any important survival benefit or risk related to chronic use of calcium channel blocking agents should be discernable through an analysis of a large database of stable recipients of renal allografts who had enrolled in a large international trial.Methods: A retrospective analysis of 4,110 renal transplant recipients who enrolled in the international Folic Acid for Vascular Outcome Reduction in Transplantation trial between 2002 and 2007 and were followed until 2010 was undertaken comparing cohorts (FAVORIT) of patients either taking (n=1,436) or not taking (n=2,674) calcium channel blocking medications. The endpoint was all-cause mortality (cardiovascular, noncardiovascular mortality, or unknown). Results were adjusted for country, age, race, sex, smoker, systolic blood pressure, diabetes mellitus, low-density lipoprotein, and chronic kidney disease status.Results: There were no statistically significant differences in incidence rates of cardiovascular, noncardiovascular, and all-cause mortality between patients taking or not taking calcium channel blocking medications.Conclusion: Although physiologic reasoning and small series results suggest a benefit for calcium channel blocking agents for allograft protection and sepsis prevention in immunosuppressed patients, we find no clear survival benefit in a large international renal transplant trial. Keywords: sepsis, immunosuppression, allograft survival, kidney transplant, calcium channel blockade, mortality