Clearing the air: smoking status in kidney transplantation assessment – a question of risk or equity?

Over the past two decades, the number of individuals receiving treatment for end-stage kidney disease (ESKD) in Australia has doubled. Although the prevalence of kidney transplantation also increased twofold during this period,¹ the kidney transplant waiting list has remained long due to persistent disparities between organ supply and demand. Between 2018 and 2023, the national median waiting time for kidney transplantation increased from 2.1 to 2.5 years.² As a result, 1330 patients remained on the kidney transplant waiting list in 2023.^{1, 2} Amid this growing need, the eligibility of active smokers has remained a subject of ongoing debate.

In this issue of the Internal Medicine Journal in a retrospective study conducted within a local health district in New South Wales (NSW) Australia, Hazim et al. examined a cohort of 333 patients receiving maintenance dialysis, of whom ~25% were identified as current smokers.³ Among the overall cohort, 150 individuals were referred for transplant assessment. Smoking was cited as the primary reason for exclusion from the transplant waitlist in 14.4% of cases. Of the 89 patients who were current smokers, 48 were not referred for transplant assessment. Within this subgroup, smoking status alone accounted for exclusion in 10 cases, while both smoking and the presence of comorbidities contributed to exclusion in 38 cases. The outcomes of smokers who did receive pre-transplant assessment were not discussed. This study found that patients who were active smokers tended to be younger (47.8 years vs. 52.1 years) and had a lower burden of comorbid conditions compared to those excluded for other reasons. Specifically, individuals excluded due to smoking had a lower prevalence of diabetes mellitus, coronary artery disease, peripheral vascular disease and heart failure. In addition to the retrospective analysis, the study incorporated a national survey of Australian transplant units, which revealed that approximately 30% of centres did not exclude patients from waitlisting solely because of active smoking. The survey also identified substantial variability in clinical practice related to the assessment and management of smoking, including differences in the use of self-reported smoking status versus biochemical verification (serum cotinine measurements) and assistance for smoking cessation. The authors concluded that rigid smoking policies may inadvertently exclude individuals who would otherwise be suitable transplant candidates, potentially contributing to inequities in access to care – particularly among populations with lower socioeconomic status or indigenous background.

It is well established that tobacco use is a leading and preventable cause of mortality in the general population. In the Global Burden of Disease study, there were an estimated 6.18 million (9.1%) deaths attributable to smoking in 2021.⁴ In a large prospective study, smoking was responsible for >24 000 deaths annually (~66 deaths per day) in Australian adults aged 45 years and over and was estimated to be responsible for 15.3% of deaths among Australians in this age group in 2019.⁵ In addition to increased risk of cancer and cardiovascular diseases, there is also a substantial body of evidence implicating smoking as a risk factor for progressive kidney dysfunction. A systematic review of 15 prospective cohort studies in the general population reported increased risk of incident chronic kidney disease (CKD) and development of end-stage kidney disease (ESKD) in current or former smokers compared to those who never smoked.⁶ Similar findings have been reported in CKD populations. A post hoc analysis of the SHARP trial and a prospective study in Korean CKD patients reported that smoking significantly increased risk of mortality and progressive decline in kidney function.^{7, 8} More importantly, the Korean study demonstrated a strong dose–response relationship between number of pack-years smoked and kidney outcomes and that longer duration of smoking cessation resulted in attenuated hazard ratios for adverse kidney outcomes, which suggests that quitting cigarette smoking may be a potential modifiable factor to delay CKD progression. The precise mechanism for the nephrotoxic effects of cigarette smoking is not well understood but is likely to include the induction of multiple pro-fibrotic processes within the kidney, including endothelial dysfunction, pro-inflammatory, oxidative stress, glomerulosclerosis and tubular atrophy.⁹

In the field of kidney transplantation, there is also strong observational evidence that cigarette smokers have poorer post-transplant outcomes compared to non-smokers. In one of the largest studies of >41 000 patients from the United States Renal Data System, incident smoking after transplant was associated with a 1.46-fold and 2.32-fold increased risk of death-censored graft loss and death, respectively.¹⁰ Another cohort study from the United States reported that >25 pack-years of active smoking at the time of transplant was associated with a 30% increased risk of graft failure and that the adverse effects of smoking seemed to dissipate 5 years after cessation.¹¹ Based on these findings, the 2020 Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines on the Evaluation and Management of Candidates for Kidney Transplantation suggest cessation of smoking for at least 1 month prior to kidney transplantation.¹² However, there is considerable variation across international guidelines. In Canada, active smokers can be waitlisted for transplant if they acknowledge the increased risks and provide informed consent.¹³ Similarly, only 38% of US transplant centres consider current smoking an absolute contraindication,¹⁴ with many allowing smokers on the transplant list with adherence to smoking cessation protocols. The Transplantation Society of Australia and New Zealand (TSANZ) takes a more conservative stance and lists smoking as an absolute contraindication for kidney transplantation.¹⁵

This study underscores two key considerations. First, it demonstrates that exclusion from kidney transplant waitlisting based solely on smoking status may limit access to optimal therapy for patients with ESKD who are otherwise medically suitable and potentially appropriate transplant candidates. While there is substantial evidence outlining the adverse effects of smoking on transplant outcomes, the use of smoking status as a sole exclusion criterion may disproportionately affect specific patient populations. Such an approach risks inadvertently delaying transplantation, thereby prolonging time on dialysis and its associated morbidity, mortality and healthcare costs.¹⁶ Second, the findings of the nationwide survey reveal considerable variability in clinical practices among transplant units across Australia, mirroring patterns observed internationally. These discrepancies underscore the ethical and practical challenges in balancing the principle of equity – ensuring fair access to transplantation – with the principle of utility, which aims to optimise transplant outcomes.

Therefore, an increased emphasis is required on both patient and healthcare provider awareness regarding the impact of smoking in kidney transplantation. In parallel, structured support should be made available to facilitate smoking cessation. Referral for transplant assessment should not be withheld based on smoking status; rather, this juncture presents a critical opportunity to deliver targeted counselling and initiate evidence-based smoking cessation interventions. Several high-quality meta-analyses have demonstrated the effectiveness of smoking cessation programmes to promote long-term abstinence.¹⁷

Additionally, alternative tobacco products such as vaping devices (including e-cigarettes) and smokeless tobacco have rapidly come into use. The health risks associated with vaping and smokeless tobacco differ significantly from those of traditional cigarettes. While vaping devices and e-cigarettes are often marketed as a “safer” alternative, research has shown that they still pose considerable health risks, including respiratory irritation, cardiovascular effects and potential long-term harm to the lungs and other organs.^{18, 19} Similarly, smokeless tobacco products, while not associated with the harms of inhaled smoke, carry their own risks, including an increased likelihood of oral cancers and other mouth-related health issues.²⁰ What remains unclear, however, is the full impact of these emerging products on kidney transplantation outcomes, including graft survival, cardiovascular health and overall post-transplant morbidity. As the landscape of tobacco use continues to evolve, so too must our approach to transplant eligibility, ensuring that all forms of tobacco use are appropriately considered in the context of kidney transplantation.

As with most things in medicine, a nuanced approach is needed. Transplant programmes should adopt individualised risk assessments, consider smoking within the broader context of medical and psychosocial health and prioritise engagement, education and support to help patients with smoking cessation. We can, and must, do better.