Outcomes Among Undocumented Immigrant Kidney Transplant Recipients in California

This cohort study evaluates outcomes among undocumented immigrant kidney transplant recipients in California.


Introduction
In 2014, there were an estimated 11 million undocumented immigrants (UI) living in the US, of which 2.6 million resided in California.Approximately 6500 of these UI have end-stage kidney disease (ESKD). 1 Access to consistent dialysis for UI across the US is variable.Although all individuals are guaranteed dialysis in the event of an acute life-threatening condition through the Emergency Medical Treatment and Active Labor Act at Medicare-participating hospitals, outpatient maintenance dialysis is not covered for UI in most states.Medicare covers costs for maintenance dialysis and kidney transplant (KT) for US residents (UR), but not for UI.This is despite the fact that both maintenance dialysis and KT are substantially more cost-effective options and provide better outcomes for patients with ESKD compared with emergency-only dialysis.Therefore, access to maintenance dialysis and KT for UI is dependent upon state legislation.
California is one of the few states that use state funds to provide UI with access to maintenance dialysis and KT.A study that investigated the outcome of Medicaid-funded KT in UI receiving transplants in the US between 1999 and 2011 showed that of the 10 495 KT recipients, 346 were UI, of which the majority, 244 patients, received a transplant in California. 2 Although this study had demonstrated that UI have a nonsignificantly lower risk for graft loss compared with UR (hazard ratio [HR], 0.67; P > .05)after adjustment for recipient and transplant characteristics, there still is an overbearing, long-held perception that UI have worse transplant outcomes due to financial and social issues.Kidney transplant outcome among UI in California, where there is the highest number of UI, has not been evaluated yet. 2 With only 1 academic transplant center in Orange County, California, this single-center study at the University of California, Irvine, was conducted to compare KT outcomes of UI and UR to elucidate the association of residency status with KT outcomes.

Data Source and Study Population
This is a single-center cohort study of patients who received a KT at the University of California, Irvine, between January 1, 2012, and September 1, 2019.To minimize the impact of COVID-19 on our study, the follow-up date was set to March 1, 2020.To allow for a minimum follow-up time of 6 months, patients receiving KT after September 1, 2019, were excluded from this study.One patient who never regained consciousness after KT was excluded from the study.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline and was approved by the University of California, Irvine, institutional review board.
Because of the nature of the data collected, informed consent was waived by the institutional review board.Each individual's medical record was reviewed to retrieve information on race (Asian, Black, White, other [other included American Indian, Pacific Islander, and unknown]), ethnicity, citizenship status, donor type and characteristics, number of transplants, body mass index (calculated as weight in kilograms divided by height in meters squared), transplant characteristics, and pretransplant comorbidities including diabetes, cancer, hypertension, coronary artery disease, stroke, and heart failure.Race was self-reported and was included in this study as it is an important demographic factor that can influence graft outcome.Donor characteristics, including donor age, sex, race, ethnicity, Kidney Donor Profile Index (KDPI), presence of diabetes or hypertension, and birthplace, were gathered manually from the United Network for Organ Sharing.Hypertension was determined by ascertaining the diagnosis by health care practitioners during the pretransplant period or taking any antihypertensive medication for blood pressure control.Transplant characteristics included type of transplant, panel reactive antibody (PRA), Human Leukocyte Antigen (HLA) mismatch, cytomegalovirus infection risk, KDPI, and cold ischemic time.A zero-HLA mismatch (0MM) was based on a mismatch in the HLA-A, B, and DR loci.

JAMA Network Open | Surgery
Outcomes Among Undocumented Immigrant Kidney Transplant Recipients in California

Exposure and End Points
The primary exposure of this study was citizenship status.UI were defined as immigrants residing in the US without permission or legal documentation.UR included both US citizens and permanent residents, as both are eligible for California State and federal Medicare funding for KT.The primary end point was all-cause graft loss defined as the return to dialysis, need for a second KT, or death.The secondary end points were all-cause mortality and acute kidney allograft rejection determined by for-cause kidney allograft biopsy, which demonstrated acute cellular rejection, acute antibody-mediated rejection, or borderline changes.

Statistical Analysis
Values are reported as mean and SD.We used the t test, χ 2 test, and Fisher exact test to evaluate differences between UR and UI groups as appropriate.Kaplan-Meier analysis was used to examine the association of citizenship status with all-cause mortality, graft loss, and rejection.Cox proportional hazards regression analysis was used to examine the risk of all-cause mortality according to citizenship status.Survival analysis competing risk using Fine-Gray subdistribution model was used to examine the risks for all-cause graft loss and rejection with death and death plus graft loss as competing risks, respectively.Due to the low number of study outcomes, the Cox proportional hazard and cause-specific HRs were only adjusted with clinically relevant single variables, which included recipient characteristics (age, sex, race, ethnicity, dialysis duration, and pretransplant comorbidities including diabetes, stroke, hypertension, coronary artery disease, heart failure, cancer, dyslipidemia, and obesity), donor characteristics (age, sex, ethnicity, presence or absence of diabetes or hypertension, and terminal serum creatinine level), and transplant characteristics (type of transplant [living vs deceased donor KT (DDKT vs LDKT) and donation after brain death or cardiac death], cytomegalovirus serostatus, cold ischemia time, HLA mismatch, 0MM, induction immunosuppressive medications, panel-reactive antibody, and delayed graft function).
Analyses were performed using R studio software version 1.4.1106 with the following packages: survival, ggplot2, ggpubr, survminer (R Project for Statistical Computing).Differences were considered statistically significant at P < .05.Data were analyzed from October 2020 to August 2021.

Patient Demographics and Transplant Characteristics
Of the 446 patients who received a transplant at the University of California, Irvine, between January 1, 2012, and September 1, 2019, 114 patients were UI (Table 1).UI were more likely to be of younger age and less likely to have pretransplant diabetes compared with UR.Although half of the UR were Hispanic, up to 95% of UI were Hispanic.No difference was found in dialysis modality between the 2 groups; however, the UI group exhibited a significantly longer dialysis duration (mean [SD], 6.00 [0.37] in UR vs 7.10 [0.37] in UI; P = .04),and although 5% of patients in the UR group received preemptive transplants, no UI fell into this category.
UI were less likely to undergo LDKT (30% in UR vs 18% in UI; χ 2 1 = 5.65; P = .02)(Table 1).Deceased donor kidneys of the UI group had longer cold ischemic times, but there was no difference in KDPI between the 2 groups.PRA profiles of UR and UI did not differ significantly; however, although the rate of transplant for UI was 15% compared with 8% in UR, this difference was not statistically significant (χ 2 1 = 1.94;P = .16).In addition, UI had an only 8% rate of high risk for cytomegalovirus, compared with 17% among UR, but this difference was not statistically significant (χ 2 2 = 5.61; P = .06).95% CI, 0.99-17.91;P = .05).In both cases (all transplants and DDKT only), the increased risk for all-cause mortality was attenuated and became nonsignificant when adjusted for recipient demographics, comorbidities, or transplant characteristics (eTable 5 and eTable 6 in Supplement 1).

Discussion
This cohort study compared KT outcomes of UI and UR who received transplants at the University of California, Irvine, between 2012 and 2019.UR had a significantly increased unadjusted risk for all-cause graft loss (192%) and all-cause mortality (343%).These results became nonsignificant and were mostly attenuated when adjusted for age and ethnicity, suggesting that the lower age and Hispanic ethnicity more frequent in the UI group were the primary drivers of reduced mortality.
There were no significant differences in DAGL and rejection between the 2 groups.
The findings from our study are partly in line with previously reported results that demonstrated that UI had a lower risk for transplant graft loss compared with UR.The study by Shen et al, 2 which examined Medicaid-insured KT outcomes in adult nonresident aliens in the US between

Table 2 .
Primary and Secondary Outcomes a 1990 and 2011, found that of the 278 779 adult patients, 346 patients were UI, and that nonresident aliens had a less than 45% lower unadjusted risk for all-cause graft loss (HR, 0.48; 95% CI, 0.35-0.65),DAGL (HR, 0.55; 95% CI, 0.39-0.79),and death compared with US citizens at 5 years (HR, 0.42; 95% CI, 0.26-0.67).Limiting the inclusion criteria to only Medicaid patients likely results in the representation of only a subgroup of UI who have stronger family and financial support and are able to better navigate the health care system, thus limiting the generalizability of the study.Similarly, a single-center study 3 of 289 pediatric KT recipients in California found that even after adjusting for recipient, donor, and transplant characteristics, UI children had a 62% lower adjusted risk for Figure.Kaplan-Meier Curve for All-Cause Mortality, All-Cause Graft Loss, and Rejection for All Transplants a Number of events and incidence rates for all study outcomes.JAMA Network Open | SurgeryJAMA Network Open.2023;6(2):e2254660.doi:10.1001/jamanetworkopen.2022.54660(Reprinted) February 13, 2023 5/11 Downloaded From: https://jamanetwork.com/ on 09/28/2023 Downloaded From: https://jamanetwork.com/

on 09/28/2023 transplant
4oss compared with permanent residents and US citizens at 5 years (HR, 0.38; 95% CI, 0.15-0.96).Furthermore, most recently, a single center study4at the University of California, Davis reported that UI had 85.9% and 100% graft survival at 8 years for deceased and living donor transplants, respectively.All in all, these studies, along with ours, call into question the long-held belief that undocumented immigrants have worse transplant outcomes.There are a few explanations for the findings of our study.First, the better outcomes of the UI group may largely be explained by the younger age and the lower prevalence of diabetes, both of which were associated with the HR of all-cause mortality.In addition, considering that the UI group still had better outcomes, although not significant, when stratified for deceased donor kidney transplant, this may suggest that recipient characteristics play a more important role than donor kidney condition in determining KT outcomes.Thus, the younger age and lower prevalence of diabetes likely played a major role in the improved outcomes in the UI group.Importantly, these findings are in line with the nationwide study by Shen et al 2 suggesting that UI patients that receive KT are generally younger and healthier.Second, in addition to the younger age, UI patients who are

Table 3 .
Unadjusted and Adjusted Survival Rates for All Transplants a a Unadjusted and adjusted hazards ratio for all-cause graft loss, DAGL, all-cause mortality, and rejection for all transplants.