Post-transplant Follow-up Research Articles

Unique problems for the design of the first trials of transplanting porcine kidneys into humans

Over the past year, 3 scientific teams conducted experiments of genetically edited porcine organs into human recipients, 3 of whom were deceased and 1 living. In this editorial, we describe challenges for the design of initial xenotransplantation clinical trials and focus on patient selection, consent, and requisite post-transplant follow-up. Given the uncertain clinical benefit of xenotransplantation, we propose that patient selection criteria might include novel elements, such as approaching patients who have a low quality of life and a strong aversion to continued dialysis therapy. We set expectations related to the importance of informing and protecting family members and medical teams who could be exposed to zoonotic viral infection from the donor organ and/or receive unwanted publicity. Meeting these challenges in trial design and oversight will require multidisciplinary expertise, a conceptual model that extends beyond the individual patient, and creative collaboration between scientists and regulatory agencies.

Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma.

Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.

P6.01: Actuarial Perspective on the Immunosuppressive Medication Costs and Coverage for Transplant Recipients in the Argentine´S Public System: 2009-2021

Introduction: In 2007, a National Post-Transplant Follow-up Program (PNSPT) was created, which is managed by the Special Programs Coordination Unit (UCPE). One of the objectives of this Unit is to provide immunosuppressive drugs to patients with exclusive public coverage and some special programs. The PNSPT program includes stages that involve the purchase of medicines requested by the Ministry of Health (according to the history of consumption and the balance between registrations and withdrawals of the beneficiary); and the collection in Logistics Operators (medical prescription, request for medicines from each jurisdiction, distribution logistics, patient care and stock management). The cost of immunosuppressive drugs is high, highly variable, and poorly understood. Therefore, the objective of this study was to analyze the evolution of the PNSPT program in compliance with the coverage of immunosuppressive drugs. Methods: This is a descriptive study. The data was obtained from INCUCAI’s National Purchasing and Transplant Information System (SINTRA). The different program regulations were reviewed and medication shipments to the provinces registered and systematized. Subsequently, the following were evaluated annually: the number of patients in the program and the formulary; the amount of medicines distributed, the investment in US dollars made according to the prices paid for each medicine according to the purchase order of the last tender (to control the inflationary effect that occurred during the period analyzed). Results: PNSPT coverage has steadily increased from 705 patients (2009) to 4,351 (2021). Investments in medicines increased even more, going from US$1.1 million in 2009 to US$13.1 million in 2021. Thus, the direct increase in the average investment per patient doubled between the periods analyzed (2009: u $1,559.9; 2021: $3,010.6). The largest investment was in 2019 and there was a slight decrease in the following 2 years, as a result of changes in the management of the Program, related to the search for efficiency in the use and purchase of medicines. Throughout the analyzed period, the vademecum included drugs such as Everolimus, Azatriopine, Tracolimus XL, Meprednisone, Sirolimus, Thymoglobuline, Valganciclovir, Ganciclovir, Basiliximab and Belatacept; Oral sirolimus and eye drops for pre and post corneal transplant treatment. Conclusions: From the creation of the PNSPT, the INCUCAI increased the coverage and the annual investment for transplant patients with exclusive public coverage and for the beneficiaries belonging to the other coverage under the program. The expansion of the vademecum allowed patients under the program in all regions of the country to have full coverage of induction and immunosuppression drugs. Taking into account that the medication favors the patient´s adherence to the treatment, it is probable that the correct execution of the program benefits the patient, increasing the survival of the graft and the patient.

Successful treatment with daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report

BackgroundTransplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients.Case presentationA 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared.ConclusionsDaratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.

Donor Selection and Outcome for Pediatric Living Donor Kidney Transplant.

Preemptive related living donor kidney transplant carries the best outcomes for pediatric patients with end-stage kidney disease. Donor age, sex, and comorbidities are to be considered in selecting donors, including marginal extended criteria donors. Kidney size and number of vessels, to match recipient weight and vasculature, are also important parameters. Genetic screening is occasionally required according to the recipient's primary disease. Posttransplant, follow-up and assessment of living related donors are mandatory to evaluate not only the clinical parameters but also to assess quality of life and social and psychological status. In a 1-year follow-up of 50 donors at Abo El-Reesh Hospital (Cairo, Egypt), there were no significant changes in serum creatinine versus glomerular filtration rate (at normal levels), a 16% elevation of blood pressure, and a tendency of impaired glucose tolerance among female donors. Donors reported positive social and psychological effects. Prompt donor selection before transplant is crucial, and posttransplant care and follow-up are mandatory.

The Effect of the COVID-19 Pandemic in Intestinal Rehabilitation and Transplant Patients: Initial Results of the Intestinal Rehabilitation and Transplant Association's International Survey.

The Effect of the COVID-19 Pandemic in Intestinal Rehabilitation and Transplant Patients: Initial Results of the Intestinal Rehabilitation and Transplant Association's International Survey.

Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients.

Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in several solid organ transplants. We present a technically improved molecular method based on digital PCR that targets the mismatch between the recipient and donor at the HLA-DRB1 locus. Blood samples collected sequentially post-transplantation from a cohort of lung recipients were used to obtain proof-of-principle for the validity of the assay, correlating results with transbronchial biopsies and lung capacity tests. The results revealed an increase in dd-cfDNA during the first 2 weeks after transplantation related to ischemia-reperfusion injury (6.36 ± 5.36%, p < 0.0001). In the absence of complications, donor DNA levels stabilized, while increasing again during acute rejection episodes (7.81 ± 12.7%, p < 0.0001). Respiratory tract infections were also involved in the release of dd-cfDNA (9.14 ± 15.59%, p = 0.0004), with a positive correlation with C-reactive protein levels. Overall, the dd-cfDNA percentages were inversely correlated with the lung function values measured by spirometry. These results confirm the value of dd-cfDNA determination during post-transplant follow-up to monitor acute rejection in lung recipients, achieved using a rapid and inexpensive approach based on the HLA mismatch between donor and recipient.

Risk factors and incidence of cytomegalovirus viremia and disease in pediatric patients with allogeneic hematopoietic stem cell transplantation: An 8-year single-center experience in Latin America.

Cytomegalovirus infection represents a significant cause of morbidity and mortality after hematopoietic stem cell transplantation. This study aimed to evaluate the incidence of viremia and disease due to cytomegalovirus and the risk factors in pediatric patients with hematopoietic stem cell transplantation in our institution. This was a retrospective cohort of patients under 19 years of age who underwent allogeneic hematopoietic stem cell transplantation due to any indication between 2012 and 2019. The analysis included the diagnosis of cytomegalovirus viremia or disease during post-transplant follow-up, evaluation of risk factors, and outcomes. The statistical analysis included univariate and multivariate analyses, and the cumulative incidence of cytomegalovirus viremia was determined by the Kaplan-Meier method using STATA 14 statistical software. A total of 182 transplants were included. At 100 days, the cumulative incidence of cytomegalovirus viremia was 70.5%, and that of cytomegalovirus disease was 4.7%. Overall survival at 2 years was 74%, and event-free survival was 64%. The remaining demographic characteristics were not predictors of infection. There was no association between viremia and relapse or survival of the patients. Higher mortality was noted in cytomegalovirus disease. During the study period, the incidence of cytomegalovirus disease was similar to that of other pediatric reports, but the incidence of viremia was higher. Pre-emptive therapy has diminished disease rates and death due to infection. Viral load cutoff points should be standardized to guide treatment and avoid myelotoxicity.

Investigating Defects of Esophageal Motility in Lung Transplant Recipients.

BackgroundLung transplant patients are at risk of developing chronic lung allograft dysfunction (CLAD) of which bronchitis obliterans syndrome (BOS) is the most common. These patients also are noted to develop gastrointestinal (GI) disease. Gastroesophageal reflux disease (GERD) is implicated in BOS, and diagnosis and treatment of GERD may help to decrease incidence of BOS.MethodsA total of 131 lung transplant recipients with post-transplant evaluation between 2012 and 2019 were studied. Of 60 post-transplant evaluations with at least 6 months of post-transplant follow-up that included impedance testing, high-resolution manometry (HRM), and pH testing, procedures were performed according to recognized standards.ResultsOf 60 patients, 56 (93%) were alive at 1-year post-transplant. The patients were found to have high rates of GI motility diseases: 37 patients (62%) had abnormal impedance testing, 50 patients (83%) had abnormal HRM results, 22 patients (37%) had abnormal pH test results. There was associated high rejection rates in patients with abnormal esophageal motility. There were 37 patients that had abnormal impedance test results and of those 25 patients (67%) developed rejection. Fifty patients had abnormal post-transplant HRM studies, 33 (66%) had an acute cellular rejection episode. Twenty-two patients had abnormal pH results, with 14 (63%) having an acute cellular rejection.ConclusionsPatients undergoing lung transplantation were found to have increased incidence of abnormal GI motility studies of the esophagus. These patients were further found to have increased rejection rates and BOS which has been associated with worsened mortality. Developing a formalized pre- and post-transplant motility study process, using evolving technologies for these patients, may provide guidance of at-risk patients for CLAD and early treatment to prevent CLAD.

FC 114: Monoclonal Gammopathy in Kidney Transplanted Patients: Novel Insights into Long-Term Outcomes

Abstract BACKGROUND AND AIMS As in the general population the prevalence of monoclonal gammopathies (MG) in kidney transplant (KT) candidates increases with age. Little is known about the epidemiology and long-term consequences of MG on overall survival, graft outcomes and infectious and neoplastic complications in patients undergoing KT. METHOD We retrospectively identified patients with MG at the time of transplant (KTMG) or appearing de novo after the KT (DNMG) in 3059 patients who underwent a KT from January 2007 to June 2019 at Necker Hospital Paris (N = 1978) and from January 1998 to December 2017 at CHU Poitiers, France (N = 1081). Using a propensity score, we established a control cohort of KTMG from Necker Hospital, matched on the main covariates influencing post KT outcomes. RESULTS We identified 70 (2.3%) KTMG and 114 (3.7%) DNMG patients, presenting with identical demographic characteristics except for an older age in KTMG (62 versus 57 years; P = 0.03). MG isotypes among the 184 KT recipients with MGUS were IgG (n = 117, 64%), IgA (n = 16, 9%) or IgM (n = 16, 9%). Interestingly, DNMG patients presented more frequently with bi- or triclonal MG than KTMG patients (n = 28, 25% versus n = 7, 10%, respectively; P = 0.02). At the time of KT, among 62 patients with available sFLC measurement in KTMG, 11 (17%) had an abnormal kappa/lambda ratio. Because of systematic evaluation of SPEP during follow-up, we observed that MG disappeared during follow up more frequently in DNMG compared to KTMG (n = 51, 45% versus n = 17, 24%, respectively; P = 0.007). Figure 1 represents the results of SPEP during follow-up. FIGURE 1: Monoclonal gammopathy timescale. Serum protein electrophoresis follow-up from KT;each patient is represented by one line. Blueand green lines represent negative SPEP, performed before and after the detection of MG, and red lines represent positive SPEP with MG identification. Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft. Overall survival was poorer in KTMG than in DNMG (87 versus 176 months; P &amp;lt; 0.001). Cox model including age, sex, rank of transplantation and KTMG or DNMG revealed that age, rank of transplantation and KTMG were independent risk factors for death. Graft survival, occurrence of rejection and haematological complications were comparable between the two groups. To better evaluate the effect of MGUS at the time of KT, KTMG patients from Necker Hospital were compared with matched KT recipients. There was no difference between KTMG and controls regarding the main baseline predictors of post-KT outcomes except for lower level of residual gammaglobulins [7.5 g/L (IQR 6–9.9)] in KTMG versus 10.7 g/l (IQR 8.9–13.1) in controls (P &amp;lt; 0.0001). KTMG patients developed more frequently solid cancers (15% versus 5%; P = 0.04) and bacterial infections (63% versus 48%; P = 0.08). There was no significant difference regarding survival, frequency of rejection or haematological complications. However, KTMG patients with an abnormal kappa/lambda ratio at the time of KT tended to have poorer overall survival than those with normal kappa/lambda ratio and controls (respective medians 72, 87 and 103 months; P = 0.08) (Figure 2). CONCLUSION We report here the largest cohort of KT recipients who underwent systematic SPEP screening at the time of KT and yearly during post-transplant follow-up. We observed that MGUS prevalence in KT candidates is close to that reported in the general population. We confirm that outcomes of patients harboring MGUS at the time of KT are similar to those of matched controls without MGUS, supporting that MGUS should not be a contraindication for KT. Nevertheless, we observed that KTMG patients developed more frequently and earlier solid cancers and infections, suggesting that MGUS is associated with a relative immunodeficiency in these patients. We also showed that patients with abnormal sFLC kappa/lambda ratio experienced poor outcomes, claiming for systematic measurement of sFLC in the pre-KT workup. Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft.

MO988: Malignancy After Kidney Transplantation: A Two-Center Experience

Abstract BACKGROUND AND AIMS Kidney transplantation (KT) is the preferred treatment option for patients with end-stage renal disease (ESRD) as it provides better patient survival and quality of life. While longer graft survival is maintained with potent immunosuppressive drugs used to prevent allograft rejection, de novo malignancy development after transplantation has become a substantial issue. In this study, we aimed to investigate the incidence and risk factors of post-transplant malignancy in kidney transplant recipients, including its demographic, clinical and laboratory features. METHOD A retrospective cohort study was conducted at two tertiary care kidney transplant centers in the same province. We recruited adult (&amp;gt;18 years of age) kidney transplant recipients who underwent kidney transplantation between 1986 and 2020. We excluded KT recipients who lost to follow-up in the early post-transplant period and/or with incomplete records. Malignancies that occurred after graft failure were also excluded. Kidney transplant recipients with malignancy were matched to KT recipients without malignancy using a 1:1 ratio. RESULTS In this study, 2750 eligible patients were reviewed for the development of malignancy after kidney transplantation. A total of 278 KT recipients (10.1%) had biopsy confirmed malignancies during the follow-up period. The median post-transplant follow-up time was 217 months (IQR: 148–290 months). The most common malignancies were nonmelanoma skin cancer (28.8%), urinary tract cancer (16.5%), Kaposi's sarcoma (9.7%), gastrointestinal tract cancer (6.5%) and post-transplant lymphoproliferative disease (6.5%). The median time from kidney transplantation to the diagnosis of malignancy was 127 months (IQR: 62–198 months). In comparison to the control group, patients with malignancy were older (P ≤ 0.001), had a higher family history of malignancy (P ≤ 0.001), had a greater history of smoking (P = 0.005), and usage of erythropoietin in the pre-transplant period was higher (P ≤ 0.001). There was no significant difference between the two groups in terms of gender and the type of induction therapy. Overall mortality was higher in patients with malignancy (OR: 2.491 [CI: 1.586–3.912], P &amp;lt; 0.001). CONCLUSION The most common malignancy in kidney transplant recipients was found to be non-melanoma skin cancer. Elderly recipients, patients with a family history of malignancy and patients using erythropoietin in the pre-transplant period should be closely monitored for the development of malignancy.

Effect of Bronchoscopic Interventions on Long-Term Lung Function Among Lung Transplant Recipients due to Cystic Fibrosis: A Single-Center Study

Patients with end-stage lung disease owing to cystic fibrosis may require lung transplant, provided other therapeutic options were exhausted. During the posttransplant period, bronchial anastomoses' healing may sometimes be complicated and require bronchoscopic intervention (BI). The main aim of this study was to assess BI and its effect on long-term lung function among cystic fibrosis lung transplant recipients who have reached 2-year survival. This retrospective study includes 22 patients with cystic fibrosis who underwent primary double lung transplant in a single center between 2018 and 2020 and have checked in for their 2-year follow-up visit. BI is defined as performing endoscopic bronchoplasty through balloon dilatation, cryoprobe, argon plasma, and/or laser treatment. All patients, who did not require BI during the first year, did not need bronchoplasty during the second posttransplant year as well. Results of forced expiratory volume in 1 second as percentage of predicted value and the 6-minute walk distance were similar at 2-year follow-up to those obtained at the end of 1 year for all patients. Significant time effects were observed for forced vital capacity (FVC) (weak effect), FVC as percentage of predicted value (weak effect), and forced expiratory volume in 1 second/FVC (moderate effect). Patients who had never had bronchoscopic intervention owing to airway stenosis, as well as those who did in the first posttransplant year, maintained forced expiratory volume in 1 second as percentage of predicted value at a comparable level at the second posttransplant year follow-up visit. The number of BIs significantly decreased among patients, who were undergoing such procedures during the first posttransplant year.

Chronic Lung Allograft Dysfunction: More Than Meets the Eye?

<h3>Purpose</h3> Currently, chronic lung allograft dysfunction (CLAD) is defined as the presence of an irreversible or partly reversible (to ≤ 80% of baseline) decline in FEV1 compared with baseline FEV1 values, persistent for at least 3 months. In established CLAD, total lung capacity (TLC) and chest computed tomography (CT) are required to determine the CLAD phenotype, as this has therapeutic and prognostic significance. Current CLAD phenotypes comprise bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS), Mixed, or Undefined (in patients who do not fit in either of the other phenotypes). However, some patients may present with persistent (> 3 months) chest CT abnormalities suggestive for chronic lung allograft injury/remodelling, without clear spirometric evidence of physiologic lung allograft impairment. <h3>Methods</h3> We report a series of 7 lung transplant recipients demonstrating chronic radiological abnormalities comparable to that seen in CLAD (RAS/mixed), after exclusion of other underlying causes for the observed radiological abnormalities, yet without (significant) pulmonary function decline. <h3>Results</h3> All patients had clear, persistent (> 3 months) radiological signs of chronic lung allograft injury/remodelling, however, not qualifying for formal CLAD diagnosis (i.e. FEV1 decline ≥ 20% from baseline), but instead looming in the potential CLAD area (FEV1 decline ≥ 10% from baseline) or even presenting with normal spirometry on regular pulmonary function testing. <h3>Conclusion</h3> A subgroup of lung transplant recipients may atypically present with chronic parenchymal/interstitial (‘RAS-like') abnormalities on chest CT, without qualifying for the phenotypic definition of CLAD, according to current consensus. This warrants further reflection on the role of spirometry for detection of interstitial lung disease after lung transplantation, the potential need for regular chest CT during post-transplant follow-up, and accuracy of the current CLAD definition regarding physical lung allograft characteristics.

Transcriptome Analysis in Infections Post Heart-Transplantation

<h3>Purpose</h3> The aim of our study is to investigate a possible transcriptomic signature to discriminate the inflammatory infiltrate observed in monitoring endomyocardial biopsies (EMBs) in post-transplanted patients with or without Citomegalovirus (CMV) viremia. <h3>Methods</h3> We selected 16 patients who underwent cardiac transplantation in our centre between January 2018 and December 2020 and monitored for CMV infection and allograft rejection. We identified three groups: a control group (n=5) with patients negative at BEM for rejection and CMV infection, a rejection group (n=5) with patients positive at BEM for Acute Cellular Rejection (ACR, ≥3A-2R ISHLT grade) but negative for CMV viremia and an infection group (n=6) with patients positive at BEM for ACR (≥1A-1R ISHLT grade) in the setting of CMV viremia (>1000 copies/mL).We extracted total RNA from FFPE-EMBs and performed a transcriptome profiling by a microarray platform (Clariom-S) without any bias of transcript selection. Then, we analysed the messenger RNA profile using TAC (Transcriptome Analysis Console) software. <h3>Results</h3> The bioinformatic analysis showed differential expressed genes among the three groups (gene level fold change <-2 or >2). Notably, 293 genes were differentially expressed between Control and Infection groups (82 up-regulated and 211 down-regulated), 407 genes between Control and Rejection groups (126 up-regulated and 281 down-regulated) and 18 genes between Infection and Rejection groups (10 up-regulated and 8 down-regulated) (p-value <0.005). After, we investigated the role of the single genes, identified in the latter comparison, that could discriminate between infection and rejection in WikiPathways. This analysis revealed that these genes are mainly involved in cardiomyocytes metabolism, Il-7 signalling, regulatory circuits of the STAT3 signalling, DNA replication and cardiac progenitor differentiation pathways. <h3>Conclusion</h3> This is a first explorative but promising analysis that identified new transcriptomic signatures that could discriminate between rejection and infection in post cardiac transplant follow-up.

The ISHLT CLAD Consensus is Broadly Applicable in Stem Cell Transplant

<h3>Purpose</h3> Pulmonary chronic graft-versus-host disease (PcGvHD) is a devastating complication of allogeneic hematopoietic stem cell transplant. The 2014 NIH cGvHD Consensus Criteria only describe the obstructive phenotype of PcGvHD. On the other hand, the 2019 ISHLT Chronic Lung Allograft Dysfunction (CLAD) criteria define obstructive, restrictive and mixed phenotypes of CLAD after lung transplantation. In this study, we adapted the 2019 ISHLT criteria to define phenotypes of PcGvHD and compare its performance to the NIH criteria. <h3>Methods</h3> 350 consecutive patients enrolled on a cGVHD natural history protocol (NCT00092235) were included. We adapted ISHLT CLAD criteria by using populational predictive PFT, instead of within subject best PFT. An independent committee of one transplant hematologist, two transplant pulmonologist, and one cardiothoracic radiologist reviewed clinical data to adjudicate subjects for PcGvHD based on the CLAD-PcGvHD or NIH Criteria (Table 1). <h3>Results</h3> Over a median 112.5 (range, 8-392) months of post-transplant follow-up, half of the patients met the CLAD-PcGvHD criteria (n=166), including 12 (3.4%) obstructive, 67 (19.1%) restrictive, 47 (13.4%) mixed, and 40 (11.4%) undefined. Less than half of them (n= 78) met NIH PcGvHD Criteria (NIH+); the rest (n=88) did not (NIH-) mainly due to restriction without obstruction on PFT. The NIH+ and NIH- groups were similar in age, Karnofsky performance status, race, HCT indication and regimen, and cGvHD severity. The NIH- group had more male recipients, skin and joints/fascia cGvHD (64.8% vs 44.9%, 84.1% vs 65.4%, 77.3% vs 57.7%, respectively, all p<.05) than the NIH+ group. Overall survival post-HCT were similar between the NIH+ and NIH- groups, but significantly poorer than the no CLAD-PcGvHD subjects (figure 1). <h3>Conclusion</h3> The CLAD-PcGvHD criteria identified high risk patients with PcGvHD that were missed by the NIH criteria. The proposed criteria could become a valuable clinical tool in studying lung disease in cGvHD.

Evolution of Kidney Disease in Single Ventricle Patients After Cardiac Transplantation

<h3>Purpose</h3> Unlike Fontan-associated liver disease, the impact of heart transplant (HT) on Fontan associated kidney disease has not been well described. In this single center study, we sought to characterize the natural history of chronic kidney disease in a small cohort of Fontan patients from listing to follow up after HT. <h3>Methods</h3> We conducted a retrospective review of pediatric patients at our institution with prior Fontan palliation that underwent HT between 2000-2020. We collected demographic information, data regarding baseline renal function/anatomic abnormalities, presence of protein losing enteropathy/liver disease/renal insufficiency/diabetes, and cardiac hemodynamics. Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Cr) using the Cr-based "Bedside Schwartz" formula which was used to determine the stage of kidney disease. We trended data at listing, at transplant, and then at post-transplant follow-up visits (90 days, 180 days, then annually). <h3>Results</h3> Fourteen patients with prior Fontan palliation who underwent HT were identified. At listing, 10 out of 14 patients were noted to have a normal eGFR (GFR ≥ 90). By transplant, four of these patients declined to Stage 2 kidney disease (GFR 60 - 90, not inclusive). All four normalized by 1 year follow-up. The <b>4</b> patients with eGFR < 90 at listing all had further decline in renal function by the time of HT. Post-transplant, 2 normalized, 1 remained with eGFR <90, and 1 required dialysis. The progression of eGFR of all the patients is summarized in the figure below. <h3>Conclusion</h3> In this small single center series, Cr based eGFR at listing and at transplant appear to be risk factors for progressive renal insufficiency in Fontan patients undergoing HT. The predictive value of other pre-transplant variables is limited by our population size. Cr-based eGFR calculations may help identify Fontan patients at increased risk for a decline in renal function post HT who may benefit from enhanced longitudinal renal surveillance.

Rapid Access in Donation After Circulatory Death (DCD): The Single-Center Experience With a Classic Pathway in Uncontrolled DCD Algorithm

In Poland, 95% of organs for transplantation come from donation after brain death (DBD). In 2010, Poland officially joined the European countries in which donation after circulatory death is accepted by law. Currently, the Pomeranian Medical University Transplant Center is the only active location for uncontrolled donation after circulatory death (uDCD) in Poland. To estimate the results of uDCD kidney transplantation with a classical approach to organ recovery, we analyzed data from an early phase of uDCD program. Prospective observation of uDCD kidney allografts (group 1; n=8) compared with DBD kidney allografts (group 2; n=30). The organ recovery protocol was set up on rapid abdominal access without regional perfusion before procurement. The organs recovered from uDCD during a 24-month period increased the volume of kidneys transplanted at the center by 9.2%. Delayed graft function was diagnosed in 100% vs 46% of allografts (P=.03), respectively. Nevertheless, early posttransplant follow-up did not reveal any graft loss or recipient death cases in the DCD group. After 12 months of follow-up, the mean glomerular filtration rate was 44.5 vs 57.9 mL/min (P < .02), respectively. Crucial factors for acceptable results of uDCD are strict pretransplant assessment of recovered organs and efficient coordination of the transplant team. Conservative recovery protocol in uDCD under strict prerequisites is feasible to consider in the organ procurement pathway. Preliminary results provide space for an increase in the organ donor pool.

Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes.

BackgroundWhile Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN.MethodsWe included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort. The relationships between AGPN and patient and graft survival were analyzed with a time-dependent multivariate Cox model.ResultsThe cumulative incidence of AGPN was 20.9%. A first episode of early AGPN is associated with a non-significant increase in the risk of graft failure (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 0.90 to 1.79). Though, cumulative number of AGPN episodes (HR = 1.51; 95% CI, 0.89 to 2.57 for two episodes and HR = 2.08; 95% CI, 1.17 to 3.69 for three or more episodes) is associated with an increased risk of graft failure. In contrast, when the first episode of AGPN occurred late (i.e., 6 months post transplantation), the risk of graft failure is significantly increased (HR = 2.25; 95% CI, 1.65 to 3.07), and this risk remains relatively stable with the recurrence of late AGPN episodes. The onset of late AGPN were also associated with a higher risk of patient death. ConclusionThis analysis shows that late AGPN and recurrent AGPN are both risk factors for a poor long-term graft outcome and mortality. Late AGPN should not be considered benign infections in post-transplantation follow-up.

Outcomes of 6 Human Leukocyte Antigen-Mismatched Living Donor Kidney Transplant: A Study With Biopsy Amendment.

In this study, we examined the graft and patient survival outcomes in patients with end-stage kidney disease who received 6 HLA-mismatched incompatible living donor kidney transplant. Patients who underwent living donor kidney transplant between January 2010 and March 2020 were evaluated retrospectively. Group A included kidney transplant recipients with 6 HLA mismatches, and group B included kidney transplant recipients with 0 to 5 HLA mismatches. Patients with <1 year of follow-up were excluded. All rejection episodes were diagnosed via Tru-Cut biopsy and histopathological evaluation. There were 15 patients in group A and 176 patients in group B. The mean follow-up was 54.1 ± 30 months. The number of patients who underwent pretransplant immune desensitization and received tacrolimus-based triple maintenance immunosuppression therapy was significantly higher in group A. In group A, there were 13 acute rejections seen in 9 patients (81<); in group B, there were 67 acute rejections seen in 51 patients (28.9<; P = .019). No differences were observed between the groups in terms of baseline glomerular filtration rate (60 ± 16 vs 61.6 ± 20 mL/min/1.72 m2; P = .76), final control glomerular filtration rate (60.7 ± 15 vs 58 ± 19 mL/ min/1.72 m2; P = .59), graft loss (0< vs 4<; P = .94), and mortality (6.6< vs 3<; P = .39). The presence of 6 HLA mismatches was associated with higher rates of biopsy-proven acute rejection. However, 6 HLA-mismatched incompatible living donor kidney transplant can be safely performed in centers where posttransplant followup is supported by indication and protocol biopsies and where there is a pathological infrastructure with extensive knowledge and experience.

The Effects of CNI and Mtori-Based Regimens on Bone Mineral Density After Renal Transplantation.

Background: Since glucocorticoids are used in low maintenance doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis has become clinically significant in osteoporosis after solid organ transplantation. However, there is evidence that the mammalian target of rapamycin inhibitors (mTORi) may be beneficial via osteoclast inhibition. Objective: The bone mineral density (BMD) changes are investigated in renal transplant patients under CNI or mTORi-based maintenance regimens during the first five-year post-transplant course. Methods: This study consists of thirty-three renal allograft recipients with less than one year of dialysis history. The exclusion criteria were: being older than 50 years old, history of bisphosphonate use, parathyroidectomy, CNI-mTORi switch after the post-transplant third month, diuretic use, and history of malignancy. First and fifth-year BMD scores and simultaneous laboratory parameters were evaluated. Results: CNI (n=21) and mTORi group (n=12) had similar demographics, dialysis vintages, first and fifth-year serum parathormone, calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur neck scores of the CNI group decreased from -0.82 (±0.96) to -1.52 (±0.92) (p=0.020). We observed a significant decrease in the CNI group compared to the mTORi group [-0.70 (±0.68) and 0.30 (±0.36), respectively; p<0.01] when the BMD score changes were evaluated among years. The mean femur neck score of the mTORi group increased insignificantly from -1.13 (±0.65) to -0.82 (±0.56) at the fifth-year DXA scan (p=0.230). Similar trends were also observed in L1-4 scores. Conclusion: Our study suggests that CNI-based treatment is associated with decreased femur neck BMD scores, and mTORi-based treatment tends to be beneficial in the post-transplant five-year follow-up.