Date of Award

January 2022

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Maricar Malinis

Abstract

Although there have been improved outcomes for kidney transplant recipients, infection is still a leading cause of morbidity and mortality for long-term kidney transplant survivors (LTKS). This thesis and study aims to investigate the epidemiology of very late onset infections (>10 years post-transplant), or VLOI and clinical markers that can predict these infections.

A single-center, retrospective study of a cohort of patients (≥18 years old) who underwent kidney transplantation between 2003-2009 and survived for at least 10 years post transplantation was conducted. The primary outcome studied was the occurrence of VLOI. The data collected included transplant data, patient co-morbidities, and clinical data regarding VLOI. Multivariate analysis was used to analyze risk factors for VLOI and a predictive nomogram of infection risk was generated.

There were 327 LTKS in our cohort. Of those, there were a total of 192 VLOI among 99 LTKS. Urinary tract infections (n = 82, 43%), lower respiratory tract infections (n = 41, 21%), and gastrointestinal infections (n = 24, 13%) were the most common types of infections recorded. VLOI were most commonly due to bacterial infections (n = 152, 78%). There were 13 (7%) opportunistic infections as well. Of the 99 LTKS with at least one VLOI, half developed sepsis (as defined by SIRS criteria + source for infection) while 10% died within 30 days after diagnosis. Although not statistically significant, there was a trend towards increased mortality at comparable timepoints for LTKS with a VLOI compared to those without (p = 0.068). Independent risk factors for incidence of VLOI included older age at time of transplant, longer follow-up from time of transplant (independent of age), lower absolute lymphocyte count, and diabetes.

In summary, VLOI occurred in 30% of LTKS. These were typically due to bacterial infections and occasionally due to opportunistic pathogens. Sepsis and death were common outcome in this cohort. A predictive model incorporating determined risk factors could be utilized to identify the survivors of kidney transplant who are at greatest risk for VLOI.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/29/2023

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