Effect of Living-Donor Tobacco Smoking on Kidney Transplant Graft Survival

Background: The widening gap between kidney transplant demand and available donors has driven efforts to expand the donor pool to include individuals with risk factors such as smoking. Current evidence on the impact of living donor smoking on transplant outcomes is conflicting, leading to inconsistent transplant center policies. This study aimed to evaluate the association between living donor smoking behavior and recipient and graft survival. Methods: We conducted a retrospective cohort study using the Organ Procurement and Transplantation Network (OPTN) database, including 93,109 individuals who underwent first-time, living donor kidney-only transplantation between June 2004 and June 2022. Donor smoking behavior was defined in four ways: any history of smoking, current smoking status, pack-year history, and duration of abstinence. The primary outcome was all-cause graft loss, analyzed using multivariable Cox proportional hazard models. Secondary outcomes of delayed graft function and first year acute rejection were analyzed using multivariable logistic regression. Models were adjusted for donor, recipient and transplant characteristics. Results: Compared to recipients of grafts from non-smoking donors, those with donors who had any smoking history had an increased hazard of all-cause graft loss (HR 1.13, 95% CI 1.09-1.16, p<0.001). Donor smoking abstinence associated with a lower hazard ratio of graft loss compared to active smoking (HR 1.10, 95% CI 1.07-1.14 vs HR 1.20, 95% CI 1.14-1.26, both p<0.001). No significant association was found between abstinence duration and graft loss. Donor smoking history was also associated with increased odds of first-year acute rejection (OR 1.18, 95% CI 1.11-1.25, p<0.001). Grafts from donors with ≥21 pack-year smoking history conferred the highest risk across all outcomes: graft loss (HR 1.29, 95% CI 1.21-1.37], p<0.001), delayed graft function (OR 1.33, 95% CI 1.12-1.59, p=0.001), and acute rejection (OR 1.31, 95% CI 1.16-1.48, p<0.001) compared those from non-smoking donors. Conclusion: Cigarette smoking in living kidney donors is a risk factor for all-cause graft loss, with the greatest risk observed among recipients of grafts from donors with a significant pack-year smoking history. However, the increased risk appears to be modest when the smoking history is minimal or the donor has abstained from smoking prior to donation.