Faculty Bibliography

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.

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.

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell-mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.

Transplantation benefits from appropriate regulation by ensuring adherence to quality and safety standards. However, Dr. Andreoni highlights in his Personal Viewpoint the unintended consequences of heightened regulatory control¹ . While the article has a US perspective, its message is global. For example, in the UK any center with statistical deviation in actual-versus-expected 30-day survival outcomes can be investigated. US data show that discard rates have risen and the number of patients waiting for transplants has flattened in the era of enhanced regulation; suggesting we are providing fewer transplant opportunities for patients who could potentially benefit.

Data describing the clinical progression of coronavirus disease 2019 (COVID-19) in transplant recipients are limited. In New York City during the surge in COVID-19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID-19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID-19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID-19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID-19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID-19 outcomes among transplant recipients.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low level evidence. The number of prospective randomized trials for the treatment of AMR is small and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated.At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes and outcomes were discussed. The evidence for different treatments was reviewed and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented.Whilst it was agreed that the aims of treatment are to preserve renal function, reduce histological injury and reduce the titer of donor specific antibody (DSA), there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

Rationale & Objectives/UNASSIGNED:Recent data demonstrate that center volume is not a factor in the outcomes of adult kidney transplant recipients. This study assessed whether center volume affects graft survival in pediatric patients who received a kidney transplant. Study Design/UNASSIGNED:Case-cohort study. Setting & Participants/UNASSIGNED:Kidney transplantation centers, recipients younger than 18 years. Results/UNASSIGNED: = 0.02. Although outcomes for deceased donor kidney recipients were similar in the 3 volume categories, outcomes in patients who received a living kidney donation were better in the high-volume centers. Low household income was associated with poorer outcomes. However, 3-year graft survival was similar in the 3 center volume categories in high and low mean household income states. Limitations/UNASSIGNED:Lack of information for complications and individual family household income of recipients. Conclusions/UNASSIGNED:Transplantation outcomes are worse in pediatric patients treated at lower-volume centers. The difference was more pronounced for patients receiving living versus deceased donor kidneys. The distribution of household income in pediatric transplant recipients may also be a factor that contributes to lower 3-year graft survival in low-volume centers.

Background: Clinical trials have demonstrated the safety of utilizing hepatitis C viremic donors (HCV+) to expand the donor pool through transplantation into hepatitis C naive recipients (HCV-). However, there has been a lack of enthusiasm to of er HCV+ pancreas grafts to HCV- recipients. We of ered HCV- pancreas patients the option to list for HCV+ donor organs.
Material(s) and Method(s): Patients undergoing pancreas transplant evaluation had informed consent by a transplant physician to receive HCV+ donor organs. We ensured patients had pharmacy coverage for post-transplant HCV anti-retroviral therapy prior to listing. In our early experience, 4 of our 8 transplant recipients elected to list for HCV+ donor organs.
Result(s): In the first 8 months, the average time to transplant from listing was 41 days for patients with standard listing and 21 days for patients listing for HCV+ organs (p<0.05). Of note, 2 of the 4 HCV- recipients were blood type AB and had shorter match time due to their blood type. For all HCV+ donors, COD was anoxia/drug OD, all were HCV antibody and NAT positive, PHS IR, and national imports, with average rank of 3 on the match run. All HCV- donors were local donors with average rank of 21 on the match run. HCV+ donors were younger (28 years) in contrast to HCV- donors (35 years). All recipients have excellent graft function with no signif cant dif erences in complications, LOS, or readmissions.
Conclusion(s): Utilization of HCV+ pancreas donors has allowed our patients increased access to high quality pancreas donors with signif cantly shorter wait times