Kidney Transplant Outcomes Associated With the Use of Increased Risk Donors in Children

Sarah J. Kizilbash; Michelle N. Rheault; Qi Wang; David M. Vock; Srinath Chinnakotla; Tim Pruett; Blanche M. Chavers

Disclosures

American Journal of Transplantation. 2019;19(6):1684-1692. 

In This Article

Method

The institutional review board of the University of Minnesota approved this study.

Data Source

We utilized data from the Scientific Registry of Transplant Recipients (SRTR) for this study. The SRTR data system includes data on all donors, waitlisted candidates, and transplant recipients in the United States, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), US Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors.[14]

IRD Definition

IRDs are individuals who may have a newly acquired HIV, hepatitis B, or hepatitis C infection even though they test negative on ELISA or NAT. These donors may result in an inadvertent transmission of these viruses through transplant. CDC first published guidelines to identify IRDs in 1994. Originally, the guidelines were intended to identify individuals who were at an increased risk of HIV infection. In July 2013, these guidelines were updated to become more inclusive of the risk factors associated with hepatitis B and C infections, and to decrease the duration of high-risk behavior from preceding 5 years to 12 months. Table 1 compares 1994 and 2013 guidelines for IRD identification.[3] We determined the IRD status of donors for this study by using the following SRTR variable, "Does the Donor meet CDC guidelines for High Risk for an organ donor."

Study Population

In 2004, OPTN mandated IRD designation on the deceased donor recovery form. We used the SRTR dataset to identify all kidney transplant recipients, aged younger than 18 years, who received a deceased donor transplant in the United States between January 1, 2005 and December 31, 2015. We classified transplant recipients into two groups based on whether or not their donors met the CDC criteria for IRD. Our study cohort included 328 deceased donor recipients with an IRD kidney and 4850 recipients without an IRD kidney.

Study Variables

Donor variables. We compared the following donor characteristics between IRD and non-IRD recipients: donor age, gender, race, BMI, KDPI, cause of death, expanded criteria donor status and donation after cardiac death status. We defined the expanded criteria donors as those older than 60 years of age, or over 50 years of age with two of the following; high blood pressure, serum creatinine greater than 1.5, and/or stroke as the cause of death. We also assessed donors' viral statuses for HIV, hepatitis B, and hepatitis C. We calculated kidney donor profile index (KDPI) for each donor to determine the risk of kidney failure for a given donor compared with a reference donor.

Recipient variables. We compared the following kidney transplant recipients' characteristics between IRD and non-IRD donors: age at transplant, gender, race, calculated panel reactive antibody (cPRA) at transplant, peak cPRA, pretransplant dialysis, cause of ESRD and blood type.

Study Outcomes

We compared patient and graft survival between IRD and non-IRD recipients. To compare patient survival, we followed patients from the date of transplant to the earlier of the date of death or end of SRTR follow up. For graft survival, we followed the patients from the date of transplant to the earliest of the date of graft loss, date of death, or end of SRTR follow-up.

To evaluate the survival benefit that a pediatric candidate would derive from accepting an IRD kidney compared with remaining on the waitlist and not accepting an IRD kidney, we used a sequential stratification or sequential Cox approach.[15–17] Our goal was to assess residual survival (survival after accepting an IRD kidney vs. had they remained on the waitlist instead of accepting the IRD kidney). For each IRD recipient, we created a comparison group comprising all candidates, aged younger than 18 years, who were active on the waitlist on IRD recipient's transplant date. We followed each IRD recipient and his/her respective comparison group from the recipient's transplant date to the earlier of the date of death or end of SRTR follow-up. For patients in the comparison group who subsequently received an IRD or a living donor transplant, we censored the follow up at IRD and the living donor transplant. We created comparison groups for each of the 328 IRD recipients. Each IRD recipient and his/her comparison group was considered a different "experiment" (also termed "stratum" or "landmark").

We compared the incidence of delayed graft function (defined as the need for dialysis during the first week posttransplant), acute rejection within the first year posttransplant, disease recurrence after transplant and posttransplant malignancy between IRD and non-IRD recipients. For those who lost their graft or died, we compared the causes of graft loss or death between IRD and non-IRD recipients.

For acute rejection, we used both the transplant forms and the follow-up forms in the SRTR database to identify variables that indicated acute rejection. We followed patients for acute rejection until the earliest of the date of graft loss, date of death or end of SRTR follow up. We designated the date the form was filled as the date of acute rejection.

Statistical Analysis

We compared the continuous variables using the Wilcoxon rank-sum test and categorical variables using Chi-square or Fisher's exact test. We used Kaplan-Meier and log rank test to compare patient and graft survival between IRD and non-IRD donors. We used the Kaplan-Meier survival analysis to report survival estimates at 1, 3, and 5 years posttransplant. We also used Kaplan-Meier and log rank to compare the incidence of acute rejection within the first year posttransplant.

To compare patient and graft survival between IRD and non-IRD recipients, we conducted the Cox regression analyses, adjusting for recipients' age, gender, race, pretransplant dialysis, and cPRA. To evaluate survival benefit after IRD transplant compared with remaining on the waitlist and not accepting an IRD kidney, we performed the Cox regression analysis stratified on each experiment and adjusted for age, gender, race, pretransplant dialysis, cPRA, ABO blood type, and transplant center. Since candidates could be included in more than one comparison group, robust or sandwich standard errors were used. We performed our analyses in SAS 9.3 (SAS Institute, Cary, NC) and considered a P < .05 as statistically significant.

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