Page 48 - JCTR-11-2

Journal of Clinical and
Translational Research CMV secular trends and race

1. Introduction 2. Methods

Kidney transplantation stands as the cornerstone 2.1. Study design and patients
treatment for individuals with end-stage kidney disease This single-center, longitudinal cohort study included
1
Compared to those who remain on dialysis, recipients of kidney transplant recipients who underwent transplantation
both living and deceased donor kidneys exhibit enhanced between January 2012 and June 2021. Eligible patients were
long-term survival rates and improved quality of life. those identified as kidney recipients at the study institution
2
However, this therapeutic approach necessitates lifelong transplanted within the study timeframe and excluded if
immunosuppression to mitigate the risk of cellular and they received liver, heart, lung, intestine, or bone marrow
antibody-mediated rejection, consequently predisposing transplants. Exclusion criteria included age under 18 years
recipients to a heightened susceptibility to infections. at the time of transplant, inability to link to the institution’s
3
Among these infectious risks, cytomegalovirus (CMV) corporate data warehouse to gather clinical information
infection emerges as a common concern in kidney from the electronic health record, and repeat transplant
transplant recipients, with a remarkable 70 – 90% of adults recipients during the study timeframe. Patients were
anticipated to be CMV seropositive. 4-6 longitudinally followed until graft loss, death, or the study
The impact of African-American (AA) race on access to endpoint (June 2022), providing a minimum of 1 year of
and outcomes associated with kidney transplantation has post-transplant follow-up.
been well-studied. AAs have significantly reduced access 2.2. Primary exposure, outcomes, and definitions
7-9
to kidney transplantation, with delayed referrals and lower
rates of evaluation, listing, and transplantation compared The primary dependent exposure variable in this study was
to Caucasians. 10-12 Post-transplant, AAs experience higher race, defined as AA versus non-AA. The main outcomes of
rates of acute rejection and graft loss, 13-15 with allografts interest were CMV D+/R− serostatus and CMV infection.
lasting about half as those in Caucasians. However, studies CMV serostatus was determined using qualitative
9
assessing the influence of AA race on CMV serostatus, CMV immunoglobulin G results from both donor and
infection risk, access to anti-CMV prophylaxis, and recipient at the time of transplant. The following outcomes
associated outcomes are lacking, particularly in D+/R− definitions were used for this study:
patients. 16-19 AAs are underrepresented in clinical trials (i) CMV infection: Defined as plasma CMV polymerase
related to kidney transplantation and CMV research. 16-19 chain reaction (PCR) ≥1,000 IU/mL, with nucleic
CMV serostatus is correlated with geography and living acid amplification techniques calibrated to the World
conditions, which differ by race, suggesting that AAs Health Organization’s International Standard for
17
might have higher rates of CMV seropositivity (R+) and Human CMV.
thus lower CMV infection and disease risks, but this is not (ii) CMV disease: Defined as the presence of organ
well-studied. A small single-center study demonstrated dysfunction in the setting of CMV infection with
20
CMV infection rates of 7.5% in 80 AA kidney transplant biopsy-proven presence of CMV in the affected organ
recipients, with 15% being D+/R−, all receiving induction using DNA hybridization.
and valganciclovir prophylaxis. However, without (iii) Probable or likely refractory CMV infection: Defined
15
comparisons to other racial or ethnic groups, the as CMV viremia that increases more than 1 log in
10
implications are unclear. Beyond this, studies assessing CMV DNA levels from initial viral load after at least
15
the risk and outcomes of CMV infection by AA race in 2 weeks of appropriately dosed antiviral therapy.
contemporary kidney transplantation are also lacking. 16-19 (iv) CMV antiviral drug resistance: Defined as viral genetic
Given the current focus on health equities and racial alteration that decreases susceptibility to one or more
antiviral drugs.
justice within healthcare and society, conducting studies (v) Acute rejection: Defined as a renal allograft biopsy
that better understand the influence of AA race on CMV
serostatus, anti-CMV prophylaxis use and access, infection showing at least borderline grade according to Banff
criteria.
rates, and associated outcomes is crucial.
(vi) BK infection: Defined as BK viremia of at least 2,000
Thus, the study aims to elucidate the secular trends in copies/mL.
the incidence of CMV D+/R− mismatching and assess (vii) Severe BK infection: Defined as BK viremia of at least
whether these trends are influenced by AA race, with 10,000 copies/mL.
significant implications for clinical outcomes such as (viii) BK nephropathy: Defined based on the pathology
rejection rates, BK virus infection, and death-censored report from the kidney allograft biopsy.
graft loss. (ix) Non-CMV and non-BK infections: Defined as

Volume 11 Issue 2 (2025) 42 doi: 10.36922/jctr.24.00067