How does smoking affect kidney health and what are the best methods to quit smoking to reduce the risk of worsening kidney function and other smoking-related health issues?

Smoking and Kidney Health: Impact and Cessation Strategies

Smoking is a major modifiable risk factor that accelerates chronic kidney disease (CKD) progression, increases cardiovascular mortality, and worsens graft survival in transplant recipients—all patients with kidney disease must be screened for tobacco use at every visit and offered evidence-based smoking cessation interventions including nicotine replacement therapy and pharmacotherapy, which are safe and effective in this population. 1, 2

How Smoking Damages the Kidneys

Direct Kidney Effects

• Smoking independently predicts faster CKD progression across all causes of kidney disease, with dose-dependent and time-dependent effects 1, 3
• Nicotine activates non-neuronal nicotinic acetylcholine receptors in kidney tissue, generating reactive oxygen species and activating pro-fibrotic pathways that directly damage kidney cells 4
• Smoking causes proteinuria (protein in urine) and reduces glomerular filtration rate in the general population across different ethnicities 3
• Current smokers with non-dialysis CKD have significantly higher risk of cardiovascular events compared to never smokers, particularly in those with preserved kidney function (eGFR ≥45 mL/min/1.73 m²) 1

Transplant-Specific Risks

• In kidney transplant recipients, smoking is an independent risk factor for patient death, graft failure, ischemic heart disease, cerebrovascular disease, peripheral vascular disease, congestive heart failure, and post-transplant malignancies 1
• The prevalence of smoking at time of transplantation ranges from 25-50%, warranting aggressive intervention 1

Cardiovascular Complications

• Smoking causes cardiovascular disease, cancer, and chronic lung disease through well-established mechanisms 1
• The cardiovascular effects are particularly devastating in CKD patients who already have elevated baseline cardiovascular risk 1

Evidence-Based Smoking Cessation Methods

Screening Protocol

• Screen all kidney disease patients for tobacco use at every clinical visit, including during initial hospitalization for transplantation 1, 2
• Ask about tobacco use history (start/stop dates), amounts, types of tobacco used, and prior quit attempts 1
• Hospitalization provides an optimal window for intervention, as screening and counseling during hospitalization is more effective than usual care 1

Pharmacotherapy Options

Nicotine Replacement Therapy (NRT)

• Five nicotine replacement products are effective and can be used in combination in CKD and transplant patients: patch, gum, lozenge, nasal spray, and inhaler 2
• No dose adjustment is needed for impaired kidney function—the benefits of smoking cessation far outweigh any theoretical risks from nicotine replacement 2
• No drug interactions exist between nicotine replacement therapies and immunosuppressive agents in transplant patients 1, 2
• Combination therapy (e.g., patch plus gum) can be used for maximum effectiveness 2
• Common pitfall: Using NRT with a nicotine patch may cause more nausea, vomiting, headache, dizziness, and fatigue than patch alone, but this should not prevent combination therapy if needed for successful cessation 5

Bupropion

• Bupropion is metabolized in the liver and excreted by the kidneys 6
• In patients with renal impairment (GFR <90 mL/min), consider reduced dose and/or dosing frequency as bupropion and metabolites may accumulate 6
• Monitor closely for adverse reactions indicating high drug or metabolite exposures 6
• No contraindications exist for use with immunosuppressive medications 1

Varenicline

• Varenicline is cleared renally and requires dose adjustment in kidney disease 5
• For patients with kidney problems or on dialysis, prescribers should use a lower dose 5
• Three dosing strategies are available: traditional quit date approach, gradual reduction approach, or flexible quit date between days 8-35 of treatment 5
• Monitor for neuropsychiatric symptoms including mood changes, agitation, or suicidal thoughts, and discontinue if these occur 5

Counseling Approach

• Provide clear, strong, and personalized advice to quit at every visit 1
• Assess willingness to quit and assist by developing a specific quit plan 1, 2
• Arrange follow-up visits, referral to specialized smoking cessation programs, or pharmacotherapy 1
• Urge avoidance of secondhand smoke exposure at work and home 1

Benefits of Smoking Cessation

Kidney-Specific Benefits

• Former smokers have lower risk of cardiovascular events than current smokers, though the benefit varies by CKD stage 1
• Smoking cessation slows CKD progression and ameliorates proteinuria 7, 3
• Quitting may help prevent development of CKD in at-risk individuals 7

Overall Health Benefits

• Randomized controlled trials demonstrate that smoking cessation interventions reduce mortality in the general population 1
• Cessation reduces risk of cardiovascular disease, cancer, and chronic lung disease 1

Clinical Implementation Algorithm

1. Screen at every visit: Ask about current tobacco use, type, amount, and quit attempts 1, 2

2. For current smokers: Provide strong personalized advice to quit immediately 1

3. Assess readiness to quit:

   • If ready: Develop quit plan and initiate pharmacotherapy
   • If not ready: Continue counseling at subsequent visits and consider gradual reduction approach with varenicline 5

4. Select pharmacotherapy:

   • First-line for most patients: Combination NRT (patch + gum/lozenge) 2
   • Alternative: Varenicline with dose adjustment for kidney function 5
   • Alternative: Bupropion with dose adjustment for GFR <90 mL/min 6
   • For transplant recipients: Any of the above are safe with immunosuppressants 1, 2

5. Arrange follow-up: Schedule visits to monitor progress, adjust medications, and provide ongoing support 1, 2

6. Continue screening: Even patients who successfully quit should be periodically rescreened, as some may relapse 1

Important Caveats

• The "smoker's paradox" in dialysis patients: Some observational studies show conflicting results regarding cardiovascular risk in dialysis patients who smoke, with meta-analyses showing no increased cardiovascular event risk but increased all-cause mortality 1. However, this should not deter aggressive cessation efforts given the overwhelming evidence of harm in non-dialysis CKD and transplant populations.

• E-cigarettes are not safe alternatives: Limited evidence suggests e-cigarettes may cause albuminuria and reduced eGFR in young adults, and nephrologists should counsel against both conventional cigarettes and e-cigarettes 8

• Nicotine itself is harmful: Beyond addiction, nicotine directly damages kidneys through receptor activation and oxidative stress, making complete cessation (not just switching to "safer" nicotine delivery) the goal 4