Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome.

Background: Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. Methods: In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Results: Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P = .010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P = .217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P = .163) versus 6.4% in the primary transplantation group (P = .009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Conclusions: Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option.

Intestinal Re-Transplantation.

The history of intestinal transplantation can be traced back to the turn of the twentieth century. Although advancements have been made, the intestine still presents a greater challenge to transplantation than does that of other solid organs, experiencing higher rates of graft rejection and lower long-term survival. Increasingly, intestinal re-transplantation (re-ITx) is seen as a viable option and is now the fourth most common indication for ITx. Changes to immunosuppression protocols, technical modifications, and infectious disease monitoring have contributed to improved outcomes. The authors review the literature on re-ITx in regard to the history, management considerations, and future directions.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

A change of heart: Characteristics and outcomes of multiple cardiac retransplant recipients.

BACKGROUND: Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described. METHODS: Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. RESULTS: Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p < .001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p < .001). Mortality was highest amongst recipients aged >60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher. CONCLUSIONS: Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup.

Lung Re-transplantation after prolonged veno-venous extracorporeal membrane oxygenation (ECMO) in a child with chronic lung allograft dysfunction.

BACKGROUND: Extracorporeal Membrane Oxygenation (ECMO) may be used as a bridge to lung transplantation in selected patients with end-stage respiratory failure. Historically, ECMO use in this setting has been associated with poor outcomes Puri V et.al, J Thorac Cardiovasc Surg, 140:427. More recently, technical advances and the implementation of rehabilitation and ambulation while awaiting transplantation on ECMO have led to improved surgical and post-transplant outcomes Kirkby S et.al, J Thorac Dis, 6:1024. METHODS: We illustrate the case of a 6-year-old child who received prolonged ECMO support as a bridge to lung re-transplantation secondary to Chronic Lung Allograft Dysfunction (CLAD). RESULTS: Early rehabilitation was key in improving the overall pre-transplant conditioning during ECMO. CONCLUSIONS: Despite challenges associated with awake/ambulatory ECMO, the use of this strategy as a bridge to lung transplantation is feasible and has resulted in improved pre-transplant conditioning and post-transplant outcomes.

Off-pump lung re-transplantation avoiding clamshell thoracotomy is feasible and safe: a single-center experience.

Background: Lung re-transplantation (re-LTx) is the only therapeutic option for selected patients with advanced allograft dysfunction. This study aims to describe our center's experience to illustrate the feasibility and safety of off-pump re-LTx avoiding clamshell incision. Methods: We performed a retrospective analysis of 42 patients who underwent bilateral re-LTx between 2007 and 2021. Patients were classified according to their surgical approach and extracorporeal life support (ECLS)-use. Demographics, surgical technique, and short- and long-term outcomes were compared between groups. Continuous data were examined with an independent-sample t-test or non-parametric test. Pearson's chi-squared and Fisher's exact were used to analyze categorical data. Results: Twenty-six patients (61.9%) underwent re-LTx by anterior thoracotomy without ECLS. Compared to the more invasive approach (thoracotomy with ECLS and clamshell with/without ECLS, n=16, 38.1%), clamshell-avoiding off-pump re-LTx patients had a shorter operative time (471.6±111.2 vs. 704.0±273.4 min, P=0.010) and less frequent grade 3 primary graft dysfunction (PGD-3) at 72 h (7.7% vs. 37.5%, P=0.038). No significant difference was found in PGD-3 incidence within 72 h, mechanical ventilation, intensive care unit (ICU) and hospital stay, and the incidence of reoperation within 90 days between groups (P>0.05). In the long-term, the clamshell-avoiding and off-pump approach resulted in similar 1- and 5-year patient survival vs. the more invasive approach. Conclusions: Our experience shows that clamshell-avoiding off-pump re-LTx is feasible and safe in selected patients on a case-by-case evaluation.

Has the risk of liver re-transplantation improved over the two decades?

BACKGROUND: Despite advancements in liver transplantation (LT) over the past two decades, liver re-transplantation (re-LT) presents challenges. This study aimed to assess improvements in re-LT outcomes and contributing factors. METHODS: Data from the United Network for Organ Sharing database (2002-2021) were analyzed, with recipients categorized into four-year intervals. Trends in re-LT characteristics and postoperative outcomes were evaluated. RESULTS: Of 128,462 LT patients, 7254 received re-LT. Graft survival (GS) for re-LT improved (91.3%, 82.1%, and 70.8% at 30 days, 1 year, and 3 years post-LT from 2018 to 2021). However, hazard ratios (HRs) for GS remained elevated compared to marginal donors including donors after circulatory death (DCD), although the difference in HRs decreased in long-term GS. Changes in re-LT causes included a reduction in hepatitis C recurrence and an increase in graft failure post-primary LT involving DCD. Trends identified included recent decreased cold ischemic time (CIT) and increased distance from donor hospital in re-LT group. Meanwhile, DCD cohort exhibited less significant increase in distance and more marked decrease in CIT. The shortest CIT was recorded in urgent re-LT group. The highest Model for End-Stage Liver Disease score was observed in urgent re-LT group, while the lowest was recorded in DCD group. Analysis revealed shorter time interval between previous LT and re-listing, leading to worse outcomes, and varying primary graft failure causes influencing overall survival post-re-LT. DISCUSSION: While short-term re-LT outcomes improved, challenges persist compared to DCD. Further enhancements are required, with ongoing research focusing on optimizing risk stratification models and allocation systems for better LT outcomes.

Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation: A Novel Strategy?

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation. The pancreas allograft was removed because of progressively painful pancreatic panniculitis from clinically uncontrolled chronic rejection. The endocrine function was preserved. Induction treatment for this "islet alloautotransplantation" consisted of plasmapheresis, IVIg and alemtuzumab. At 1 year, the patient retained islet graft function with good glycemic control and absence of severe hypoglycemia, despite persistent low-grade HLA donor-specific antibodies. His panniculitis had resolved completely. In our point of view, islet alloautotransplantation derived from a chronically rejecting pancreas allograft is a potential option to salvage (partial) islet function, despite preformed donor-specific antibodies, in order to maintain stable glycemic control. Thereby it protects against severe hypoglycemia, and it potentially mitigates kidney graft dysfunction and other diabetes-related complications in patients with continued need for immunosuppression and who are otherwise difficult to retransplant.

Successful management of temporary veno-venous extracorporeal membrane oxygenation for a pediatric lung transplant recipient with bronchiolitis obliterans syndrome awaiting lung re-transplantation: a case report.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging. CASE PRESENTATION: A 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted. CONCLUSIONS: VV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Emergency, ABO-Incompatible Living Donor Liver Re-Transplantation for Graft Failure Complicated by Pneumonia-Associated Sepsis.

Although liver re-transplantation is the only therapeutic option for acute and chronic graft failure, few studies have addressed the use of ABO-incompatible living donors in the emergency setting. Here, based on our experience, we report a successful case of emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation (LDLT) for late graft failure from chronic rejection complicated by pneumonia-related sepsis. A fifty-five-year-old man had undergone LDLT for hepatocellular carcinoma accompanied by hepatitis C virus (HCV)-related cirrhosis in 30 September 2013. The voluntary donor was his 56-year-old wife, who was also a carrier of HCV. The donor and recipient blood types were the same: O and Rh positive. She underwent a right hepatectomy and was discharged on postoperative day (POD) seven. The patient was also discharged without complications on POD eleven and was followed up with on an outpatient basis. Abdominal distension and jaundice were developed at 6 months after LDLT, when the serum total bilirubin level was 2.7 mg/dL. The serum total bilirubin levels increased rapidly to 22.9 mg/dL over the next 4 months. Chronic rejection was diagnosed via liver biopsy. On 3 October 2014, he developed pneumonia-related sepsis and showed the progressive deterioration of liver function. Liver re-transplantation using the right liver from his ABO-incompatible, 20-year-old nephew was performed as an emergency in 15 October 2014. The donor blood type was A and Rh positive. The resection of the failed graft and the implantation of a new graft was performed by the intragraft dissection technique to re-use previously transplanted graft vessels in order to cope with severe adhesions. The recipient went through a gradual recovery process and was finally discharged on POD 50 with normal liver function, while the donor had an uneventful recovery and was discharged on POD 7. Biloma due to bile leak was detected three months after re-transplantation and was cured by percutaneous interventional procedures. Since then, the postoperative course has been event-free at regular outpatient follow-ups. The patient has so far had normal laboratory findings and no signs of complications. It has been 98 months since the re-transplantation, and the recipient and two donors are still in good condition with normal liver function, having complete satisfaction with the results obtained from this re-transplantation. In conclusion, long-term, satisfactory outcomes can be achieved in emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation for graft failure complicated by pneumonia-related sepsis in selected patients.

Operational tolerance after intestine re-transplantation in childhood and immunological correlates. Case report and review.

BACKGROUND: Operational tolerance after retransplantation of the intestine has never been reported. PURPOSE: To two recently described intestine transplant recipients with operational tolerance, we now add a third. METHODS: Review of case record and immunological testing to confirm donor-specific hyporesponsiveness in multiple immune cell compartments. RESULTS: Re-transplanted with a multivisceral liver- and kidney-inclusive intestine allograft at age 12 years, this recipient self-discontinued immunosuppression 14 years after the retransplant and has been rejection free for 2 years thereafter. As in the two previous reports, immunological testing demonstrated decreased donor-specific inflammatory response of T-cytotoxic memory cells and B-cells, decreased presentation of donor antigen by B-cells and monocytes, absence of donor-specific anti-HLA antibodies, circulating FOXP3 + T-helper cells, and intact cellular and humoral immunity to cytomegalovirus and Epstein-Barr virus. Additionally, our recipient demonstrated enhanced donor-activation-induced apoptosis of alloreactive T-cytotoxic memory cells. CONCLUSIONS: Despite variable paths to tolerance which include graft versus host disease in two previous cases, and rejection-related loss of the primary isolated intestinal allograft in our recipient, the three cases with operational tolerance are bound by common themes: a relatively large donor antigenic load transmitted during intestine transplantation, and donor-specific hyporesponsiveness. Cell-based assays suggest enhanced donor-induced apoptosis of recipient T-cells and circulating T-regulatory cells as mechanistic links between antigenic load and donor-specific hyporesponsiveness.

Rationale for Surrogate Endpoints and Conditional Marketing Authorization of New Therapies for Kidney Transplantation.

Conditional marketing authorization (CMA) facilitates timely access to new drugs for illnesses with unmet clinical needs, such as late graft failure after kidney transplantation. Late graft failure remains a serious, burdensome, and life-threatening condition for recipients. This article has been developed from content prepared by members of a working group within the European Society for Organ Transplantation (ESOT) for a Broad Scientific Advice request, submitted by ESOT to the European Medicines Agency (EMA), and reviewed by the EMA in 2020. The article presents the rationale for using surrogate endpoints in clinical trials aiming at improving late graft failure rates, to enable novel kidney transplantation therapies to be considered for CMA and improve access to medicines. The paper also provides background data to illustrate the relationship between primary and surrogate endpoints. Developing surrogate endpoints and a CMA strategy could be particularly beneficial for studies where the use of primary endpoints would yield insufficient statistical power or insufficient indication of long-term benefit following transplantation.

Allograft liver failure awaiting liver transplantation in Japan.

BACKGROUND: Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. METHODS: Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test. RESULTS: The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. CONCLUSIONS: Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

ABO-incompatible Repeat Kidney Transplantation: Coping with the 'Twin Immunological Barrier'.

A repeat renal transplantation is believed to confer the best survival advantage for allograft failure. The scarcity of matching donors at one end, coupled with the expanding pool of ABO-incompatible (ABOi) donors at the other end, lead us to consider the option of ABOi kidney re-transplantation. However, ABOi kidney re-transplantation is associated with heightened immunological risk due to the presence of two substantial immunological barriers. Concern, queries, and uncertainty exist over the course and outcome of this option. We prospectively studied five patients who underwent live-related ABOi re-transplantation after a failed previous transplant. Four patients (mean age 40.8 ± 6.6 years, 4 males) underwent a second renal transplant, whereas one patient had a third renal transplant. All patients received desensitization with rituximab, plasmapheresis, and intravenous immunoglobulin as per routine protocol. One patient required immunoadsorption to achieve the desired Anti-ABO titer. All five patients had good graft survival. One of them developed combined antibody and cell-mediated rejection and another antibody-mediated rejection. Live-related ABOi kidney re-transplantation could be a viable option for patients with a previously failed graft.

Clinical and Economic Impact of Previous Bariatric Surgery on Liver Transplantation: a Nationwide, Population-Based Retrospective Study.

PURPOSE: The present study aims to determine the impact of previous bariatric surgery (BS) on the length of hospital stay; the incidence of mortality, re-transplantation, and re-hospitalization after LT; and the related economic costs, through the analysis of the French National Health Insurance Information System. MATERIALS AND METHODS: All patients aged > 18 years who underwent LT in France in the period from 2010 to 2019 were included. Thirty-nine patients with a history of BS (study group) were compared with 1798 obese patients without previous BS (control group). RESULTS: At the time of LT, patients with a history of BS were significantly younger than those of the control group and had lower Charlson comorbidity index. Female sex was significantly more represented in the study group. No significant differences were detected between the two groups regarding the postoperative mortality rate after LT (10.3% in the study group versus 8.0% in the control group), long-term mortality (0.038 versus 0.029 person-year of follow-up, respectively), re-transplantation (adjusted hazard ratio (HR) = 2.15, p = 0.2437), re-hospitalization (adjusted analysis, IRR = 0.93, p = 0.7517), and costs of LT hospitalization (73,515 € in the study group versus 65,878 € in the control group). After 1:2 propensity score matching, the duration of the LT hospital stay was significantly longer in the study group (58.3 versus 33.4 days, p = 0.0172). CONCLUSION: No significant differences were detected between patients with previous BS versus obese patients without history of BS undergoing LT concerning the rates of mortality, re-LT, re-hospitalization after LT, and costs of hospitalization and re-hospitalizations.

Long-term outcomes of living-donor lobar lung transplantation.

OBJECTIVE: Although living-donor lobar lung transplantation (LDLLT) enables an intermediate survival similar to cadaveric lung transplantation, the long-term outcome remains unknown. We examined the long-term outcomes of 30 patients who received LDLLT more than 16 years previously. METHODS: We retrospectively reviewed the clinical data of 30 patients who underwent LDLLT (bilateral LDLLT, 29 patients; single LDLLT, 1 pediatric patient) between October 1998 and April 2004. RESULTS: LDLLT was performed for 25 female and 5 male patients ranging in age from 8 to 55 years. The diagnoses included pulmonary hypertension (n = 11), pulmonary fibrosis (n = 7), bronchiolitis obliterans (n = 5), and others (n = 7). At a median follow-up of 205 months, 22 patients were alive and 8 were dead. The causes of death were infection (n = 3), malignancy (n = 2), acute rejection (n = 2), and chronic lung allograft dysfunction (CLAD; n = 1). Unilateral CLAD occurred in 17 patients (56.7%), but only 1 of these patients subsequently developed bilateral CLAD. Two patients underwent bilateral cadaveric lung retransplantations. The 5-, 10-, and 15-year CLAD-free survival rates were 80.0%, 62.8%, and 44.3%, respectively. Malignancy occurred in 7 patients. Two of 5 patients with chronic kidney disease requiring hemodialysis underwent living-donor kidney transplantation. The 5-, 10-, and 15-year overall survival rates were 96.7%, 86.7%, and 73.3%, respectively. CONCLUSIONS: Although only 2 lobes are implanted, LDLLT provides encouraging long-term outcomes. In patients with unilateral CLAD, the functioning contralateral graft might contribute to a favorable long-term outcome.

Predictors of patient and graft survival following pediatric liver transplantation: Long-term analysis of more than 300 cases from single centre.

BACKGROUND: Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population. METHODS: Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival. RESULTS: Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p < .05) impact on patient survival: recipient age, weight, height, graft type (technical variant graft), transplant category (acute liver failure), the era of transplant, and invasive ventilation. The following variables had a significant (p < .05) impact on graft survival: recipient age, weight, height, transplant category (acute liver failure), and the era of transplant. Multivariate analysis precluded the era of transplant as the only significant factor for patient survival; patients transplanted after 2005 had significantly higher patient survival. No independent factor predicting graft survival was identified. For children transplanted after 2005, the only factor that predicted patient survival was pre-transplant invasive ventilation. CONCLUSIONS: Our study suggests that the learning curve and pre-transplant invasive ventilation in the recipient have a significant impact on patient survival. The traditional view of worse outcomes of smaller PLT candidates should be changed.

Chronic rejection after liver transplantation: Opening the Pandora's box.

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the "early" phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.

Re-transplantation in pediatric patients with failure of primary transplant due to recurrent focal segmental glomerulosclerosis: A pediatric nephrology research consortium study.

INTRODUCTION: Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns. METHODS: Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium. RESULTS: Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers. CONCLUSIONS: Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.