Date of Award

6-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Health Outcomes and Policy Research

Track

Health Policy

Research Advisor

Csaba P. Kovesdy, M.D.

Committee

Cameron M. Kaplan, Ph.D.; Hamid Moradi, M.D.; Frank Park, Ph.D.; Fridtjof Thomas, Ph.D.

Abstract

Background: Legalization of cannabis and its constituents may lead to increased exposure of a higher number of consumers to cannabis use, including those with chronic kidney disease (CKD). We expect increase in cannabis use, especially, in patients with compromised kidney function. However, there is sparse literature on the effects of cannabis use on cardiorenal and mortality outcomes among patients with advanced CKD. Objectives: The main goal of the current study was to examine the effect of cannabis use on renal and cerebrovascular outcomes as well as mortality in patients with advanced CKD. Using a nationwide cohort of US veterans with advanced CKD transitioning to dialysis, we were guided by the following aims: Aim 1) Evaluate the effect of cannabis exposure on kidney function by 1a) examining the association of cannabis exposure with progression of CKD, and 1b) investigating the association of cannabis exposure with the incidence of acute kidney injury (AKI); Aim 2) Investigate the association of cannabis exposure with the incidence of stroke; and Aim 3) Examine the association of cannabis exposure with mortality (mortality due to any reason and cardiovascular mortality). Methods: We used a retrospective cohort study design in a nationally representative cohort of US veterans with incident End-Stage Renal Disease (ESRD) who transitioned to renal replacement therapy from October 1, 2007 through March 31, 2015. The Transition of Care in Chronic Kidney Disease (TC-CKD) cohort consisted of 102,477 US veterans with incident ESRD identified from the US Renal Data System (USRDS). Urine toxicology tests (UTOX) determined the use of cannabis, opioids, other drugs, and combinations of the same in the patients who had undergone a UTOX test within the year prior to dialysis initiation. After applying inclusion and exclusion criteria, 7,146 patients comprised our study population. Chapter 2 discusses our examination of the association between UTOX groups and renal outcomes, including both long-term changes in estimated glomerular filtration rate (eGFR) and the incidence of AKI. We used mixed-effects models with random intercepts and slopes and logistic regression to examine the association between UTOX groups and the risk of change in eGFR and AKI, respectively. Chapter 3 describes our investigation of the association between UTOX groups and cerebrovascular accident (CVA) events using Cox proportional hazard models. Finally, Chapter 4 presents our research on the association between UTOX groups and mortality using Cox proportional hazard models (mortality due to any reason) and Fine and Grey’s competing risk regression (cardiovascular mortality). Results: Cannabis users were more likely to be younger (57 years cannabis users vs. 60 years no drug use), less likely to be white (45% cannabis users vs. 55% no drug use), and more likely to be smokers (69% cannabis users vs. 38% no drug use). We observed that cannabis use alone or combined with opioids or other drugs (vs. no drug use) was not significantly associated with steeper eGFR slopes or risk of AKI (P-value 0.4-1.0). We also found that the use of cannabis alone, opioids, other drugs alone, or a combination of these (vs. no drug use) was not significantly associated with the risk of CVA events (P-value 0.4-1.0). Finally, cannabis use alone or combined use of cannabis with opioids or with other drugs (vs. no drug use) was not significantly associated with mortality due to any reason or CV mortality (P-value 0.4-1.0). Conclusion: This study is the first, to our knowledge, to ascertain use of cannabis, opioids, or other drugs via UTOX tests to examine the association between various combinations of exposures and renal/cardiovascular/mortality outcomes in patients with advanced CKD transitioning to dialysis. The study findings suggest the absence of a harmful association between exposure to cannabis and renal/cerebrovascular/mortality outcomes. Future clinical trials and further epidemiological studies are needed to confirm these findings and further expand our understanding of the health effects of cannabis use in the general population as well as in patients with compromised kidney function.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

0000-0003-0649-6089

DOI

10.21007/etd.cghs.2020.0510

2020-019-Potukuchi-DOA.pdf (198 kB)
Declaration of Authorship

Available for download on Thursday, June 30, 2022

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