Substance Use Among Potential Kidney Transplant Candidates and its Impact on Access to Kidney Transplantation: A Canadian Cohort Study

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Substance Use Among Potential Kidney Transplant Candidates and its Impact on Access to Kidney Transplantation: A Canadian Cohort Study Evan Tang 1, Aarushi Bansal 1, Michelle Kwok 1, Olusegun Famure 1, S. Joseph Kim 1, Daniel Z. Buchman 2,3, Marta Novak 4,5 and Istvan Mucsi 1 1 Multi-Organ Transplant Program, University Health Network, Toronto, Canada 2 Department of Bioethics, University Health Network, Toronto, Canada 3 Joint Centre for Bioethics and DallaLana School of Public Health, University of Toronto 4 Centre for Mental Health, University Health Network and Department of Psychiatry, University of Toronto, Toronto, Canada 5 Institute of Behavioural Sciences, Semmelweis University Budapest, Hungary Contact: evan.tang@uhn.ca

Authors have nothing to disclose.

35 yo, African Canadian male ESKD due to GN On PD x 3 yrs, recently switched to HD No major comorbidities Lives with common law partner, stable relationship Recurrent problems with non-adherence to dialysis, drug seeking behavior, use of recr. drugs, narcotic analgesics Non-adherence to HD, no-show for several appointments Pt. was declined to be waitlisted he accepted this decision

Why are we selecting patients? Assess and minimize peri-op risk CV assessment Hemostasis Obesity Rehab potential Cognitive/psychiatry issues. Optimize post-tx outcomes Infection Rejection Malignancy Recurrence Mental health, adherence Utility survival whose decision is it?

Background Concerns about substance use (alcohol, tobacco, recreational and prescription drugs) among patients after solid organ transplant include: non-adherence to transplant medications exacerbation of underlying mental health conditions interactions between substance use and transplant medications general health consequences of substance use Negative outcomes associated with tobacco use have been demonstrated. Thus, tobacco use is discouraged but not a contraindication for kidney transplant; however, it is a contraindication for some other solid organ transplants in some centers. Active drug use is a contraindication to KT because of concerns about the negative impact on post-transplant outcomes.

Relative listing contraindications, considerations Psychosocial Considerations: Patients with an acute or untreated psychotic illness, or that display social support/compliance issues that prohibit adherence to therapy are not candidates for kidney transplantation. Psychosocial Considerations: Cognitive impairment is not an absolute contraindication to kidney transplantation. However, particular care must be taken to ensure that informed consent can be obtained and that a support system is in place to ensure adherence to therapy and patient safety. A history of psychiatric illness is not an absolute contraindication to kidney transplantation. Capacity should be evaluated when indicated. Kidney transplantation should be delayed until the patient has demonstrated freedom from substance abuse for at least 6 months.

Background and Aims We are not aware of studies exploring the prevalence of substance use (tobacco or recreational drug use, prescription drug abuse) and its impact on access to KT in a Canadian context. Access to KT includes being placed on the waitlist and being transplanted. Aims: among patients with end stage kidney disease we will describe the frequency of substance use determine sociodemographic correlates of substance use determine the impact of substance use on access to KT

Sample selection Adult patients referred for kidney transplant assessment at Toronto General Hospital between Jan 1, 2003 - Dec 31, 2012 (n = 2,584) Exclusion Criteria Patients who did not have complete social work assessment on file (n = 752) Patients who had simultaneous multiorgan transplant (n = 63) Final Study Cohort (n = 1,769)

Methods Information about substance use, socio-demographic and clinical data was obtained from Social Work notes stored in the Comprehensive Renal Transplant Research Information System (CoReTRIS). Patients were followed until Dec 31, 2013 The Ontario Marginalization Index (OMI), a census-and geographically based index was used to consider material deprivation. Missingnesswas less than 3% for all variables, except OMI (8%). Multipleimputation by chained equations to address missing data.

Methods - Exposure Substance use was categorized by substance and whether it was current or historical. Tobacco Recreational Drug Use Prescription Drug Abuse Alcohol Alcohol use was not well quantified and ubiquitous and was therefore excluded from analysis. Recreational drug use and prescription drug abuse was analyzed as one group (drug use). Current substance use was used in all analysis.

Methods Outcomes Positive final disposition was characterized as being activated on the waitlist or cleared for living donor transplant within two years from referral. Transplantwas characterized as receiving a kidney transplant.

Methods Statistical analysis The association between substance use (dependent variable) and baseline patient characteristics and was explored using multinomial logistic regression. The cumulative probabilities of time-to-outcome were graphically assessed using the Kaplan Meier product limit method, and differences across survival distributions were examined using the log-rank test. Univariable and multivariable associations between the exposure and outcome variables were explored using Cox proportional hazards models. Origin of analysis was the time of referral for kidney transplant assessment

Baseline Characteristics - 1 Variables, %(n) Total (1769) No substance use () Current tobacco use (245) Current drug use (90) P Value Mean Age (± SD) 49 (14) 50 (14) 48 (12) 40 (14) 0.020 Male 60 (1066) 59 (860) 69 (168) 69 (62) 0.001 OMI 0.967 Highest (Least deprived) 18 (312) 18 (259) 17 (41) 19 (17) Second highest 20 (359) 20 (298) 21 (51 20 (18) Mid 21 (364) 21 (309) 17 (41) 18 (16) Second lowest 16 (280) 16 (228) 19 (46) 17 (15) Lowest (Most deprived) 17 (307) 17 (253) 18 (43) 18 (16) Ethnicity <0.001 Caucasian 54 (958) 51 (746) 69 (168) 74 (67) African Canadian 13 (225) 14 (201) 7 (17) 11 (10) East-Asian Canadian 11 (191) 12 (177) 5 (13) 4 (4) South Asian Canadian 7 (121) 13 (189) 8 (19) 6 (5)

Baseline Characteristics - 2 Variables, % (n) Total (1769) No substance use (1466) Current tobacco use (213) Current drug use (90) P Value Marital Status <0.001 Single, never married 21 (371) 20 (295) 17 (36) 44 (40) Married/Common law 62 (1090) 63 (963) 59 (126) 40 (36) Divorced/Separated/Widowed 17 (298) 16 (235) 23 (50) 14 (13) Employment <0.001 Unemployed 43 (762) 41 (599) 55 (117) 51 (46) Employed 34 (594) 34 (503) 26 (56) 39 (35) Other 22 (393) 24 (346) 18 (39) 9 (8) History of mental health disorder 24 (432) 23 (334) 26 (56) 47 (42) <0.001 History of non-adherence 18 (311) 16 (231) 22 (46) 38 (34) <0.001

Multinomial Logistic Regression - 1 Current Tobacco Use Current Drug Use Variable RRR 95% CI P RRR 95% CI P Age 0.98 0.97-1 0.011 0.96 0.94-0.98 0.001 Race White Black 0.25 0.14-0.46 < 0.001 0.48 0.22-1.02 0.055 East Asian 0.24 0.12-0.47 < 0.001 0.27 0.1-0.76 0.013 South Asian 0.24 0.13-0.46 < 0.001 0.11 0.03-0.47 0.003 Other 0.73 0.42-1.28 0.271 0.49 0.17-1.42 0.19 Sex Female Male 1.6 1.16-2.21 0.004 1.94 1.19-3.18 0.008 Marital Status Married Single never married 0.65 0.41-1.03 0.066 1.67 0.92-3.03 0.089 Widowed/Divorced/Separated 1.53 1.05-2.26 0.028 1.48 0.74-2.97 0.261 Current tobacco use associated with: - Younger age - White ethnicity - Male Sex - Widowed/Divorced/ Separated individuals Current drug use associated with: - Younger age - White ethnicity - Male Sex

Multinomial Logistic Regression - 2 Current Tobacco Use Current Drug Use Variable RRR 95% CI P RRR 95% CI P Employment Status Employed Unemployed 2.04 1.42-2.96 < 0.001 1.08 0.65-1.81 0.766 Other 1.24 0.76-2.03 0.379 0.46 0.2-1.07 0.071 Ontario Marginalization Index Lowest - Poor Highest - Rich 0.89 0.53-1.51 0.676 0.88 0.38-1.99 0.75 Second Highest 0.88 0.53-1.46 0.612 0.84 0.4-1.76 0.644 Middle 0.74 0.44-1.25 0.259 0.7 0.31-1.56 0.381 Second Lowest 1.07 0.66-1.77 0.766 0.91 0.41-2 0.814 History of Mental Health Disorder No Yes 0.95 0.67-1.35 0.781 2.44 1.52-3.94 < 0.001 History of Non-Adherence No Yes 1.4 0.96-2.07 0.079 2.12 1.29-3.51 0.003 Current tobacco useassociated with: - Unemployment Current drug use associated with: - History of mental health disorder - History of non-adherence

Association between substance use and Positive Final Disposition

Multivariable adjusted association between substance use and Positive Final Disposition Cox Proportional Hazards Model Current Tobacco Use Current Drug Use Hazard Ratio (95% CI) Hazard Ratio (95% CI) Model 1 0.80 (0.65, 0.98) 0.85 (0.63, 1.13) Model 2 0.78 (0.63, 0.95) 0.76 (0.56, 1.02) Model 3 0.78 (0.63, 0.96) 0.76 (0.56, 1.02) Model 4 0.81 (0.65, 0.99) 0.82 (0.60, 1.11) Model 5 0.82 (0.65, 0.98) 0.84 (0.57, 1.04) Model 1: Model 2: Model 3: Model 4: Model 5: Univariable Model 1 plus age, ethnicity, sex, marital status Model 2 plus English communication, Ontario Marginalization Index, employment status Model 3 plus History of mental health, history of non-adherence Model 4 plus history of diabetes, coronary artery disease/ myocardial infarction, heart failure,

Association between substance use and receiving a kidney transplant

Multivariable adjusted association between substance use and receiving a kidney transplant Cox Proportional Hazards Model Tobacco Use Hazard Ratio (95% CI) Drug Use Hazard Ratio (95% CI) Model 1 0.81 (0.66, 1.00) 0.87 (0.65, 1.16) Model 2 0.72 (0.58, 0.89) 0.70 (0.52, 0.95) Model 3 0.73 (0.59, 0.90) 0.71 (0.53, 0.96) Model 4 0.75 (0.60, 0.93) 0.80 (0.59, 1.09) Model 5 0.77 (0.62, 0.96) 0.81 (0.59, 1.11) Model 1: Model 2: Model 3: Model 4: Model 5: Univariable Model 1 plus age, ethnicity, sex, marital status Model 2 plus English communication, Ontario Marginalization Index, employment status Model 3 plus History of mental health, history of non-adherence Model 4 plus history of diabetes, coronary artery disease/ myocardial infarction, heart failure,

Summary and discussion Current drug use occuredin 5% and current tobacco use occurs in 14% of our sample Tobacco use was associated with younger age, male sex, Caucasian ethnicity, widowed or divorced marital status, and unemployment. Current drug use was more frequent in patients who were younger, male, Caucasian or Black, with a history of mental health disorder and with a history of non-adherence.

Summary and discussion Those with tobacco use have a lower likelihood of receiving a positive final disposition and a transplant. Current drug use was not significantly associated with receiving a positive disposition or a transplant, however, a trend for lower likelihood was seen.

Limitations Lack of systematic method to explore and quantify substance use Potential for under-reporting and social desirability bias Incomplete or insufficient documentation of social work assessment (29%) Selected patient population patients with significant substance use problems were likely not referred for transplant assessment

Next Steps Develop a systematic approach to the pre-transplant assessment of substance use. Explore if post transplant clinical outcomes associated with pre-transplant substance use Explore the potential impact of interventions in this population to improve access to transplant and outcomes for