Evaluation of Opening Offers Early for Deceased Donor Kidneys at Risk of Nonutilization.

BACKGROUND: Reducing nonutilization of kidneys recovered from deceased donors is a current policy concern for kidney allocation in the United States. The likelihood of nonutilization is greater with a higher kidney donor risk index (KDRI) offer. We examine how opening offers for organs with KDRI >1.75 to the broader waitlist at varying points of time affects usage rates. METHODS: We simulate kidney allocation using data for January 2018 to June 2019 from Organ Procurement and Transplantation Network. For the simulation experiment, allocation policy is modified so that KDRI >1.75 organs are offered to all local candidates (same donation service area) after a set amount of cold time simultaneously. Open offers to candidates nationally are similarly examined. RESULTS: Simulation results ( n =50 replications) estimate that opening offers locally for KDRI >1.75 after 10 hours yields a nonutilization rate of 38% (range: 35%-42%), less than the prevailing rate of 55% of KDRI >1.75 kidneys. Opening offers after 5 hours yields 30% (range: 26%-34%), reducing the prevailing nonutilization rate by 45%. Opening offers nationally after 10 and 5 hours yields nonutilization rates of 11% (range: 8%-15%) and 6% (range: 4%-9%) for KDRI >1.75 kidneys, respectively. CONCLUSIONS: Simulation findings indicate that opening offers and adjusting their timing can significantly reduce nonutilization of high-KDRI kidneys.

"Advancing Face Transplantation: A Critical Analysis of Revisions and Long-Term Surgical Outcomes in Ten Cases".

BACKGROUND: Face transplantation has emerged as a viable solution for reconstructing the most complex facial injuries. Prior work has demonstrated that surgical revisions are necessary to optimize outcomes. The authors' group has updated the previous report of revisions in their cohort, quantified and described which revisions were performed for functional, aesthetic, or mixed indications, and described the rationale, safety, and long-term outcomes of these revisions. METHODS: A retrospective analysis of the authors' ten face transplants was performed from April 2009 to February 2023. The patients' medical records, preoperative facial defects, and operative reports (index and secondary revisions) were reviewed. RESULTS: Nine patients were included. One patient underwent irreversible acute on chronic allograft rejection and received a second face transplant. The average number of revisions was 5.2 per patient (range, 2 to 11 procedures). The median time interval from transplantation to first revision was 4 months (range, 1 to 21 months). Median follow-up was 106 months (range 39 to 142 months). Most interventions consisted of debulking the allograft or revising the periorbital tissues. CONCLUSIONS: In the current study, we report longer term data on revision surgeries needed in face transplant recipients. Patients should expect to undergo revisions for both functional and aesthetic considerations. Although the majority of revisions are performed within two years following transplantation, revisions can be safely performed at any time point. Shared decision-making between the patient and provider team is essential in deciding which revisions are performed and when.

Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor-free, Belatacept Plus Everolimus-based Immunosuppression.

Compared with calcineurin inhibitor-based immunosuppression, belatacept (BELA)-based treatment has been associated with better renal function but higher acute rejection rates. This phase 2 study (NCT02137239) compared the antirejection efficacy of BELA plus everolimus (EVL) with tacrolimus (TAC) plus mycophenolate mofetil (MMF), each following lymphocyte-depleting induction and rapid corticosteroid withdrawal. Methods: Patients who were de novo renal transplant recipients seropositive for Epstein-Barr virus were randomized to receive BELA+EVL or TAC+MMF maintenance therapy after rabbit antithymocyte globulin induction and up to 7 d of corticosteroids. The primary endpoint was the rate of biopsy-proven acute rejection at month 6. Results: Because of an unanticipated BELA supply constraint, enrollment was prematurely terminated at 68 patients, of whom 58 were randomized and transplanted (intention-to-treat [ITT] population: n = 26, BELA+EVL; n = 32, TAC+MMF). However, 25 patients received BELA+EVL' and 33 received TAC+MMF (modified ITT population). In the ITT population, the 6-mo biopsy-proven acute rejection rates were 7.7% versus 9.4% in the BELA+EVL versus TAC+MMF group. The corresponding 24-mo biopsy-proven acute rejection rates were 19.2% versus 12.5% in the ITT population and 16.0% versus 15.2% in the mITT population; all events were Banff severity grade ≤IIA and similar between groups. One patient in each group experienced graft loss unrelated to acute rejection. The 24-mo mean unadjusted estimated glomerular filtration rates were 71.8 versus 68.7 mL/min/1.73 m2 in the BELA+EVL versus TAC+MMF groups. Posttransplant lymphoproliferative disorder was reported for 1 patient in each group. No deaths or unexpected adverse events were observed. Conclusions: A steroid-free maintenance regimen of BELA+EVL may be associated with biopsy-proven acute rejection rates comparable to TAC+MMF.

A Composite End Point of Graft Status and eGFR at 1 Year to Improve the Scientific Registry of Transplant Recipients' Five-Tier Rating System.

BACKGROUND: Performance of kidney transplant programs in the United States is monitored and publicly reported by the Scientific Registry of Transplant Recipients (SRTR). With relatively few allograft failure events per program and increasing homogeneity in program performance, quantifying meaningful differences in program competency based only on 1-year survival rates is challenging. METHODS: We explored whether the traditional end point of allograft failure at 1 year can be improved by incorporating a measure of allograft function (i.e., eGFR) into a composite end point. We divided SRTR data from 2008 through 2018 into a training and validation set and recreated SRTR tiers, using the traditional and composite end points. The conditional 5-year deceased donor allograft survival and 5-year eGFR were then assessed using each approach. RESULTS: Compared with the traditional end point, the composite end point of graft failure or eGFR <30 ml/min per 1.73 m2 at 1-year post-transplant performed better in stratifying transplant programs based on long-term deceased donor graft survival. For tiers 1 through 5 respectively, the 5-year conditional graft survival was 72.9%, 74.8%, 75.4%, 77.0%, and 79.7% using the traditional end point and 71.1%, 74.4%, 76.9%, 77.0%, and 78.4% with the composite end point. Additionally, with the five-tier system derived from the composite end point, programs in tier 3, tier 4, and tier 5 had significantly higher mean eGFRs at 5 years compared with programs in tier 1. There were no significant eGFR differences among tiers derived from the traditional end point alone. CONCLUSIONS: This proof-of-concept study suggests that a composite end point incorporating allograft function may improve the post-transplant component of the five-tier system by better differentiating between transplant programs with respect to long-term graft outcomes.

Sustained Improvement in Patient Experience by Optimizing Patient Flow in Ambulatory Settings.

Patient experience has become a priority for healthcare institutions as it affects clinical quality of care, financial reimbursement, provider, and patient satisfaction. We report our experience of improving patient experience measured by Press Ganey surveys in a busy multidisciplinary clinic over 65 months. We optimized patient flow in the clinic by technology-facilitated communication among the clinic staff and by a modest space redesign. We noted a significant improvement in "clinic visit" scores from baseline of 82.1 to 84.6 at year 1, 86.1 at year 2, 88.7 at year 3, and 88.9 at year 4 (P < .001). In comparison with previous short-term studies, we were able to sustain improvement in patient experience scores over 4 years due to optimized patient flow and monitoring of clinic operations. A similar approach can be implemented in other ambulatory settings and is likely to cause a long-term positive impact on patient experience.

Developing simultaneous liver-kidney transplant medical eligibility criteria while providing a safety net: A 2-year review of the OPTN's allocation policy.

The OPTN's simultaneous liver-kidney (SLK) allocation policy, implemented August 10, 2017, established medical eligibility criteria for adult SLK candidates and created Safety Net kidney allocation priority for liver-alone recipients with new/continued renal impairment. OPTN SLK and kidney after liver (KAL) data were analyzed (registrations as of December 31, 2019, transplants pre-policy [March 20, 2015-August 9, 2017] vs. post-policy [August 10, 2017-December 31, 2019]). Ninety-four percent of SLK registrations met eligibility criteria (99% CKD: 50% dialysis, 50% eGFR). SLK transplant volume decreased from a record 740 (2017) to 676 (2018, -9%), with a subsequent increase to 728 (2019, 1.6% below 2017 volume). For KAL listings within 1 year of liver transplant, waitlist mortality rates declined post-policy versus pre-policy (27 [95% CI = 20.6-34.7] vs. 16 [11.7-20.5]) while transplant rates increased fourfold (46 [32.2-60.0] vs. 197 [171.6-224.7]). There were 234 KAL transplants post-policy (94% Safety Net priority eligible), and no significant difference in 1-year patient/graft survival vs. kidney-alone (patient: 95.9% KAL, 97.0% kidney-alone [p = .39]; graft: 94.2% KAL, 94.6% kidney-alone [p = .81]). From pre- to post-policy, the proportion of all deceased donor kidney and liver transplants that were SLK decreased (kidney: 5.1% to 4.3%; liver: 9.7% to 8.7%). SLK policy implementation interrupted the longstanding rise in SLK transplants, while Safety Net priority directed kidneys to liver recipients in need with thus far minimal impact to posttransplant outcomes.

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection.

BACKGROUND: Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. METHODS: Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. RESULTS: An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. CONCLUSIONS: Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.

Consensus conference on heart-kidney transplantation.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States.

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.