Faculty Bibliography

RATIONALE & OBJECTIVE:Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines. STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:A cohort of 143,750 US kidney donors between 1987 and 2017. EXPOSURE:Biological relationship of donor and recipient. OUTCOME:ESKD. Donors' records were linked to national dialysis and transplantation registries to ascertain development of the outcome. ANALYTIC APPROACH:Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used. RESULTS:Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6). LIMITATIONS:Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients. CONCLUSIONS:Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.

BACKGROUND:Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant (KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across transplant centers. METHODS:Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus continued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection, graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms. RESULTS:=0.6). CONCLUSIONS:KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings suggest ESW may lead to worse KT outcomes in recipients with DGF.

RATIONALE AND OBJECTIVE/OBJECTIVE:Compared to recipients of ABO-compatible (ABOc) living donor kidney transplants (LDKT), recipients of ABO-incompatible (ABOi) LDKT have a higher risk of graft loss, particularly in the first few weeks after transplantation. However, the decision to proceed with ABOi LDKT should be based on a comparison of the alternative: waiting for future ABOc LDKT (e.g, through kidney paired exchange) or for a deceased donor kidney transplant (DDKT). We sought to evaluate the patient survival difference between ABOi LDKT and waiting for an ABOc LDKT or an ABOc DDKT. STUDY DESIGN/METHODS:Retrospective cohort study of adults in the Scientific Registry of Transplant Recipients (SRTR) SETTING AND PARTICIPANTS: 808 ABOi LDKT recipients and 2423 matched controls from among 245,158 adult, first-time kidney-only waitlist registrants who did not receive an ABOi LDKT and who remained on the waitlist or received either an ABOc LDKT or an ABOc DDKT, 2002-2017 EXPOSURE: Receipt of ABOi LDKT OUTCOME: Death ANALYTICAL APPROACH: We compared mortality among ABOi LDKT recipients versus a weighted matched comparison population using Cox proportional hazards regression as well as Cox models that accommodated for changing hazards ratios over time. RESULTS:Compared to matched controls, ABOi LDKT was associated with lower survival risk in the first 30 days post-transplant (99.0% vs 99.6%, respectively), but higher survival risk beyond 180 days post-transplant. Patients who received ABOi LDKT had higher survival at 5 and 10 years (90.0% and 75.4% respectively) than similar patients who remained on the waitlist or received ABOc LDKT or ABOc DDKT (81.9% and 68.4% respectively). LIMITATIONS/CONCLUSIONS:No measurement of ABO antibody titers in recipients; eligibility of participants for kidney paired donation is unknown. CONCLUSIONS:Transplant candidates who receive an ABOi LDKT and survive more than 180 days post-transplant experience a long-term survival benefit compared to remaining on the waitlist to potentially receive an ABO compatible kidney transplant.

Purpose: In heart transplantation (HT), antibodies directed against Angiotensin II type 1 receptor (AT1RAb) have been associated with antibody-mediated rejection (AMR), acute cellular rejection (ACR), and microvasculopathy. The effect of AT1RAb detected pre-HT on immediate post-HT allograft injury remains poorly defined. In this study, we leverage a validated and sensitive blood based biomarker for allograft injury, donor-derived cell-free DNA (ddcfDNA), to examine the association of pre-HT AT1RAb to post-HT allograft injury.
Method(s): AT1RAb testing was performed on pretransplant plasma from HT recipients in the Genomic Research Alliance for Transplantation (GRAfT) multicenter, prospective cohort study, using a quantitative ELISA (One Lambda, ThermoFisher). After HT, serial plasma samples were collected and used to quantitate %ddcfDNA by shotgun sequencing. AT1RAb concentration (units/ml) was used to categorize patients as AT1RAb<30 (n=32) or AT1RA>30 (n=17). A mixed linear model was used to examine post-HT %ddcfDNA trajectories across AT1RAb groups. Histopathology slides were read by a consensus of pathologists to define AMR using ISHLT criteria.
Result(s): Age, gender and clinical features were similar between AT1RAb<30 and AT1RA>30 groups. AT1RAb>30 had a greater proportion of White recipients compared to AT1RAb<30 (59% versus 38%; p = 0.003). While %ddcfDNA on posttransplant Day 1 were similar between AT1RAb<30 vs AT1RAb>30 (p=0.6), in the first year post-HT, ddcfDNA declined by 87% (95% CI 79%-92%) among patients with AT1RAb<30 vs 67% (CI=34%-84%) among patients with AT1RAb>30 (p = 0.04) (Figure). AMR in the first year post-HT was more common among AT1RAb>30 than AT1RAb<30 patients (18% vs 3%, p=0.07); CMR was comparable in each group (41% vs 24%, p=0.2).
Conclusion(s): Preliminary analysis of this heart transplant cohort suggest that high pre-HT AT1RAb is associated with increased early post-HT allograft injury.
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