The hepatocyte growth factor mimetic, ANG-3777, in kidney transplant recipients with delayed graft function: Results from a randomized phase 3 trial.

In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Kidney retransplantation outcomes in adults aged 70 and older: Analysis of risk factors and survival.

BACKGROUND: An increasing number of older patients are undergoing kidney transplant. Because of a finite longevity, more patients will be faced with failing allografts. At present there is a limited understanding of the benefits and risks associated with kidney retransplantation in this challenging population. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 undergoing kidney retransplant from January 1, 2014 to December 31, 2022. We examined patient and graft survival of retransplanted patients compared to first time transplants. We also analyzed the risk factors that impacted the survival. RESULTS: During the study period there has been a significant rise in the number of retransplants performed, with 631 patients undergoing the procedure. Although clinically insignificant, overall graft, and patient survival rates were slightly lower in the retransplant group compared to the primary transplant group. With retransplant, patient survival was 91.3%, 75.6%, and 56.9% compared to 93.4%, 81.4%, and 64.4% with primary transplant at 1, 3, and 5 years, respectively. With retransplant, graft survival was 89.5%, 73.5%, 57.4% compared to 91.5%, 79.0%, and 63.6% in a primary transplant group at 1, 3, and 5 years, respectively. Multivariable analysis showed that factors predicting poor survival included longer time on dialysis before retransplantation and decreased functional capacity. No survival difference was noted between recipients of deceased versus living donor kidneys. Patients who underwent retransplantation before initiating dialysis had better patient and graft survival. CONCLUSION: Patients aged ≥70 achieve satisfactory outcomes following kidney retransplantation, highlighting that chronologic age should not preclude this medically complex population from this life-saving procedure. Improvement in functional status and timely retransplantation are the key factors to successful outcome.

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

BACKGROUND: The optimal treatment for chronic active antibody-mediated rejection (ca-AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL-6, has been proposed as a therapeutic option. We reported our experience treating ca-AMR with TCZ either as the first line option or as a rescue therapy. METHODS: We studied 11 adult kidney transplant recipients with biopsy-proven ca-AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd-cfDNA. Clinical monitoring included dd-cfDNA and DSA testing every 3 months during the treatment with TCZ. RESULTS: In this cohort, ca-AMR was diagnosed at a median of 90 months (range 14-224) post-transplant, and 4 of 11 patients had DSA negative ca-AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd-cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd- cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd-cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections. CONCLUSIONS: In our early short-term experience, TCZ appears to reduce graft injury as measured by dd-cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.

Immunosuppression in HIV-positive kidney transplant recipients.

PURPOSE OF STUDY: The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients. RECENT FINDINGS: Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided. SUMMARY: Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.

Deceased donor kidneys are discarded at higher rates when labeled as high kidney donor profile index.

The kidney donor risk index (KDRI) and percentile conversion, kidney donor profile index (KDPI), provide a continuous measure of donor quality. Kidneys with a KDPI >85% (KDPI85 ) are referred to as "high KDPI." The KDPI85 cutoff changes every year, impacting which kidneys are labeled as KDPIHIGH . We examine kidney utilization around the KDPI85 cutoff and explore the "high KDPI" labeling effect. KDRI to KDPI Mapping Tables from 2012 to 2020 were used to determine the yearly KDRI85 value. Organ Procurement and Transplantation Network data was used to calculate discard rates and model organ use. KDRI85 varied between 1.768 and 1.888. In a multivariable analysis, kidney utilization was lower for KDPI 86% compared with KDPI 85% kidneys (p = .046). Kidneys with a KDRI between 1.785-1.849 were classified as KDPIHIGH in the years 2015-2017 and KDPILOW in the years 2018-2020. The discard rate was 44.9% when labeled as KDPIHIGH and 39.1% when labeled as KDPILOW (p < .01). For kidneys with the same KDRI, the high KDPI label is associated with increased discard. We should reconsider the appropriateness of the "high KDPI" label.

Conversion from Calcineurin Inhibitor- to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b Trial.

BACKGROUND: Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients. METHODS: Stable adult kidney transplant recipients 6-60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months. RESULTS: Overall, 446 renal transplant recipients were randomized to belatacept conversion ( n =223) or CNI continuation ( n =223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, -2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m 2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder. CONCLUSIONS: Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA.Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572.

Defining the roles and responsibilities of the kidney transplant medical director: A necessary step for future training, mentoring, and professional development.

The management of a kidney transplant program has evolved significantly in the last decades to become a highly specialized, multidisciplinary standard of care for end-stage kidney disease. Transplant center job descriptions have similarly morphed with increasing responsibilities to address a more complex patient mix, increasing medical and surgical therapeutic options, and increasing regulatory burden in the face of an ever-increasing organ shortage. Within this evolution, the role of the Kidney Transplant Medical Director (KTMD) has expanded beyond the basic requirements described in the United Network for Organ Sharing bylaws. Without a clear job description, transplant nephrology trainees may be inadequately trained and practicing transplant nephrologists may face opaque expectations for the roles and responsibilities of Medical Director. To address this gap and clarify the key areas in which the KTMD interfaces with the kidney transplant program, American Society of Transplantation (AST) formed a Task Force of 14 AST KTMDs to review and define the role of the KTMD in key aspects of administrative, regulatory, budgetary, and educational oversight of a kidney transplant program.

KDOQI US Commentary on the 2020 KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation.

Evaluation of patients for kidney transplant candidacy is a comprehensive process that involves a detailed assessment of medical and surgical issues, psychosocial factors, and patients' physical and cognitive abilities with an aim of balancing the benefits of transplantation and potential risks of surgery and long-term immunosuppression. There is considerable variability among transplant centers in their approach to evaluation and decision-making regarding transplant candidacy. The 2020 KDIGO (Kidney Disease: Improving Guidelines Outcome) clinical practice guideline on the evaluation and management of candidates for kidney transplantation provides practice recommendations that can serve as a useful reference guide to transplant professionals. The guideline, covering a broad range of topics, was developed by an international group of experts from transplant and nephrology through a review of literature published until May 2019. A work group of US transplant nephrologists convened by NKF-KDOQI (National Kidney Foundation-Kidney Disease Quality Initiative) chose key topics for this commentary with a goal of presenting a broad discussion to the US transplant community. Each section of this article has a summary of the key KDIGO guideline recommendations, followed by a brief commentary on the recommendations, their clinical utility, and potential implementation challenges. The KDOQI work group agrees broadly with the KDIGO recommendations but also recognizes and highlights the decision-making challenges that arise from lack of high-quality evidence and the need to balance equity with utility of organ transplantation.

High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury.

The clinical importance of subclinical, early T cell-mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] -16.22% to -1.39%) (-3.50 mL/min/1.73 m2 IQR -8.00 to -1.00) vs 0% (-4.92%, 4.76%) in low dd-cfDNA patients (P = .004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P < .0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P = .003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Maternal obesity is associated with congenital anomalies of the kidney and urinary tract in offspring.

BACKGROUND: Congenital abnormalities of the kidney and urinary tract (CAKUT) are diagnosed in up to 1 % of pregnancies and account for 20-30 % of the abnormalities identified in the prenatal period. In previous studies, maternal obesity has been associated with congenital malformations in offspring. Our aim was to evaluate the association between maternal obesity [body mass index (BMI) ≥ 30 kg/m2] and CAKUT in offspring. METHODS: We conducted a population-based, case-control study using linked birth-hospital discharge records from Washington State, 2003-2012. We identified 3093 CAKUT cases using International Classification of Diseases, Ninth Revision (ICD-9) codes. Controls were defined as births without any ICD-9 codes denoting congenital malformations, matched to cases by year of birth in an approximate 4:1 ratio. RESULTS: Compared to controls, mothers giving birth to infants with CAKUT were more likely to be obese [odds ratio (OR) 1.24, 95 % confidence interval (CI) 1.11-1.38]. We found a significant positive trend between odds of CAKUT in offspring and increasing severity of obesity (score test for trend of odds p < 0.001). This association remained significant in offspring with isolated CAKUT (OR 1.19, 95 % CI 1.06-1.35) and upper urinary tract anomalies (OR 1.26, 95 % CI 1.13-1.41). Maternal overweight (BMI 25-29.9 kg/m2) was not associated with CAKUT in offspring. CONCLUSIONS: Our results demonstrate a positive association between maternal obesity and CAKUT in offspring, as well as between obesity severity and the odds of CAKUT in offspring. These findings provide additional evidence for the public health importance of obesity, particularly as a potentially modifiable risk factor.

Eculizumab use in kidney transplantation.

PURPOSE OF REVIEW: Eculizumab suppresses the effector functions of the complement system and represents a therapeutic breakthrough for patients with paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome (aHUS). Safety monitoring is ongoing; so far, most notable is the expected increase in infection risk with encapsulated organisms. Despite potential applicability in multiple complement-mediated disorders, the off-label use of eculizumab has been limited, mainly by its prohibitive cost. The purpose of this review is to summarize the current data relevant to the use of eculizumab in kidney transplantation. RECENT FINDINGS: In aHUS, prone to high rates of recurrence and allograft loss, eculizumab has made the most notable therapeutic impact. Further clarification of complement defects may help predict therapeutic responses and hopefully guide treatment duration. In C3 glomerulopathies, the clinical response to eculizumab appears more heterogeneous and less effective in processes mediated by upstream to C5 complement deregulation. A large clinical trial of eculizumab for prevention of delayed graft function is ongoing. In antibody-mediated rejection, the role of eculizumab is unclear as its use has been limited to very complex, mostly presensitized, patients in mixed combinations of therapeutic modalities. SUMMARY: Overall, eculizumab has raised awareness of complement-mediated disorders as an exciting, new therapeutic option with multiple potential applications in kidney transplantation. Further research is needed to develop a better understanding of eculizumab applicability, efficacy, and treatment monitoring and beyond, to future therapeutic tools targeting the complement.

Impact of Obesity on Kidney Transplant Outcomes in Older Adults.

BACKGROUND: The prevalence of obesity in older patients undergoing kidney transplantation is increasing. Older age and obesity are associated with higher risks of complications and mortality post-transplantation. The optimal management of this group of patients remains undefined. METHODS: We retrospectively analyzed the United Network for Organ Sharing database of adults ≥70 years of age undergoing primary kidney transplant from January 1, 2014, to December 31, 2022. We examined patient and graft survival stratified by body mass index (BMI) in 3 categories, <30 kg/m2, 30 to 35 kg/m2, and >35 kg/m2. We also analyzed other risk factors that impacted survival. RESULTS: A total of 14,786 patients ≥70 years underwent kidney transplantation. Of those, 9,731 patients had a BMI <30 kg/m2, 3,726 patients with a BMI of 30 to 35 kg/m2, and 1,036 patients with a BMI >35 kg/m2. During the study period, there was a significant increase in kidney transplants in patients ≥70 years old across all BMI groups. Overall, patient survival, death-censored graft survival, and all-cause graft survival were lower in obese patients compared with nonobese patients. Multivariable analysis showed worse patient survival and graft survival in patients with a BMI of 30 to 35 kg/m2, a BMI >35 kg/m2, a longer duration of dialysis, diabetes mellitus, and poor functional status. CONCLUSION: Adults ≥70 years should be considered for kidney transplantation. Obesity with a BMI of 30 to 35 kg/m2 or >35 kg/m2, longer duration of dialysis, diabetes, and functional status are associated with worse outcomes. Optimization of these risk factors is essential when considering these patients for transplantation.

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians.

BACKGROUND LCPT (Envarsus XR®) is a common once-daily, extended-release oral tacrolimus formulation used in kidney transplantation. However, there are minimal evidence-based recommendations regarding optimal dosing and treatment in the de novo and conversion settings. MATERIAL AND METHODS Using Delphi methodology, 12 kidney transplantation experts with LCPT experience reviewed available data to determine potential consensus topics. Key statements regarding LCPT use were generated and disseminated to the panel in an online Delphi survey. Statements were either accepted, revised, or rejected based on the level of consensus, perceived strength of evidence, and alignment with clinical practice. Consensus was defined a priori as ≥75% agreement. RESULTS Twenty-three statements were generated: 14 focused on de novo LCPT use and 9 on general administration or LCPT conversion use. After 2 rounds, consensus was achieved for 11/14 of the former and 7/9 of the latter statements. In a de novo setting, LCPT was recognized as a first-line option based on its safety and efficacy compared to immediate-release tacrolimus. In particular, African Americans and rapid metabolizer populations were identified as preferred for first-line LCPT therapy. In a conversion setting, full consensus was achieved for converting to LCPT to address neurological adverse effects related to immediate-release tacrolimus and for the time required (approximately 7 days) for steady-state LCPT trough levels to be reached. CONCLUSIONS When randomized clinical trials do not replicate current utilization patterns, the Delphi process can successfully generate consensus statements by expert clinicians to inform clinical decision-making for the use of LCPT in kidney transplant recipients.

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.

Intention-to-treat Analysis of Patients Aged 70 Years and Older Awaiting Kidney Transplantation in Post-Kidney Allocation System Era.

BACKGROUND: The US population is aging, and so the number of patients treated for end-stage renal disease is on the rise. In the United States, 38% of people over 65 y old have chronic kidney disease. There continues to be a reluctance of clinicians to consider older candidates for transplant, including early referrals. METHODS: We conducted a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 y old undergoing kidney transplants from December 1, 2014, to June 30, 2021. We compared patient and graft survival in candidates who were transplanted while on hemodialysis versus preemptive with a living versus deceased donor kidney transplant. RESULTS: In 2021, only 43% of the candidates listed for transplant were preemptive. In an intention-to-treat analysis from the time of listing, candidate survival was significantly improved for those transplanted preemptively versus being on dialysis (hazard ratio 0.59; confidence interval, 0.56-0.63). All donor types, donor after circulatory death, donor after brain death, and living donor, had a significant decrease in death over remaining on the waiting list. Patients who were on dialysis or transplanted preemptively with a living donor kidney had significantly better survival than those receiving a deceased donor kidney. However, receiving a deceased donor kidney significantly decreased the chance of death over remaining on the waiting list. CONCLUSIONS: Patients ≥70 y old who are transplanted preemptively, whether with a deceased donor or a living donor kidney, have a significantly better survival than those who are transplanted after initiating dialysis. Emphasis on timely referral for a kidney transplant should be placed in this population.

Anti-GSTT1 antibodies and Null genotype correlate with histological changes of antibody mediated rejection in kidney transplantation.

BACKGROUND: The presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR). METHODS: We aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor's non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30). RESULTS: At an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2-16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63-404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1-190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn't confer a higher risk of failure within the study observation period. CONCLUSION: The presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up.

Survival Benefit in Older Patients Transplanted With Viremic Hepatitis C Positive Kidneys When Compared With High KDPI Kidneys.

BACKGROUND: Because of the continued demand in kidney transplantation, organs from donors with risk criteria for blood-borne viruses, high Kidney Donor Profile Index (KDPI) kidneys, and hepatitis C virus (HCV)-positive kidneys are being considered. There continues to be reluctance on the part of the providers and the candidates to accept HCV-positive kidneys. METHODS: We conducted a retrospective analysis of the Organ Procurement and Transplantation Network database of all adult (≥18 y old) recipients undergoing kidney transplant from May 10, 2013, to June 30, 2021. We compared patient and graft survival in candidates who received HCV-positive kidneys versus non-hepatitis C (Hep C) high KDPI kidneys by estimated posttransplant survival (EPTS) groups. RESULTS: HCV-viremic kidneys were transplanted in 5.6% of patients in the EPTS >61% group compared with 5.1% of patients in the 21%-60% EPTS group and 1.9% of 0%-20% EPTS group ( P < 0.001). Of all transplants performed in the EPTS 61%-100% group, 11.9% were KDPI >85% compared with 5.2% in the EPTS 21%-60%, and 0.5% in the EPTS 0%-20%. Patient survival was significantly longer at 1, 3, and 5 y in the EPTS >61% group who received Hep C-viremic or -nonviremic allografts compared with non-Hep C kidneys with KDPI >85%. When it comes to listing, only 25% of candidates in the EPTS >61% group were listed for Hep C nucleic acid testing-positive kidneys in 2021. CONCLUSIONS: Our findings could be used for counseling candidates on the types of kidneys they should consider for transplantation. Also, listing practices for viremic Hep C kidneys need continued re-evaluation.

Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report.

BACKGROUND: The liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis. CASE SUMMARY: A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation. CONCLUSION: This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.