Chronic Graft Rejection Research Articles

Experiences and outcomes of inverted kidney transplantation from a single Vietnamese institute.

Inverted kidney transplant (KT) has been applied in many transplant centers, but the experiences and outcomes of this technique was limited. To describe the technical characteristics, indications and evaluate the outcomes of inverted kidney transplantation. Retrospective study from January 2016 to December 2023, included 74 patients who underwent inverted kidney transplantation with 72 cases of right kidney transplant into the right iliac fossa and 2 cases of left kidney transplant into the left iliac fossa performed in Viet Duc University Hospital. 63 cases in stage 1 (ipsilateral kidney transplant), all kidney graft were transplanted on the same side and 11 cases in stage 2 in which the kidney transplant was performed in some special cases such as recipients with severe atherosclerotic iliac arteries or incompatibility between the arteries and venous. The operation time was significantly higher (192.8 vs. 173.7min, p = 0.037). However, the kidney function showed no difference when being discharged and remained stable until the latest follow-up. 3-year graft survival was 98.3%. There was 1 case of graft loss due to chronic graft rejection- immunosuppression incompliance requiring retransplantation after 2 years. Main complications included acute pancreatitis (2.7%), and ureteral stenosis at the ureter-bladder junction (6.8%), not significantly different compared to conventional KT. Inverted kidney transplantation is a simple, safe and effective technique and could be a feasible solution for some specific circumstances.

NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection.

Chronic graft rejection represents a significant threat to long-term graft survival. Early diagnosis, understanding of the immunological mechanisms and appropriate therapeutic management are essential to improve graft survival and quality of life for transplant patients. Knowing which immune cells are responsible for chronic vascular rejection would allow us to provide effective and appropriate treatment for these patients. It is now widely accepted that natural killer (NK) cells play an important role in chronic vascular rejection. They can either initiate chronic vascular rejection by recognizing missing self on the graft or be recruited by donor-specific antibodies to destroy the graft during antibody-mediated rejection. Whatever the mechanisms of activation of NK cells, they need to be primed to become fully activated and damaging to the graft. A better understanding of the signaling pathways involved in NK cell priming and activation would pave the way for the development of new therapeutic strategies to cure chronic vascular rejection. This review examines the critical role of NK cells in the complex context of chronic vascular rejection.

Complications associated with kidney transplantation, causes of graft failure and mortality following kidney transplantation in patients with systemic lupus erythematosus: a meta-analysis

IntroductionDespite improvement in the management of systemic lupus erythematosus (SLE) during the past two decades, 10–22% of patients with lupus nephritis (LN) will progress to end-stage renal disease (ESRD). Kidney transplantation is among the possible treatment for patients with SLE progressing to ESRD. However, the issue with kidney transplantation in patients with SLE is controversial. In this analysis, we aimed to compare the complications associated with kidney transplantation, causes of graft failure and causes of mortality following kidney transplantation in patients with SLE with ESRD.MethodsThe sources of data included http://www.ClinicalTrials.gov, EMBASE, MEDLINE, Google Scholar, Web of Science and the Cochrane database. Revman software version 5.4 was used for the data analysis whereby risk ratio (RR) with 95% confidence intervals (CI) were used to represent data following analysis. In addition, the Q statistic test and the I2 statistic test were used to assess heterogeneity. A random effect statistical model was used and a subgroup outcome with a P-value less than 0.05 was considered statistically significant.ResultsA total number of 149,330 participants enrolled between the years 1968 and 2018 were included in this analysis with 7534 participants with SLE.Results of this analysis showed that mortality (RR 1.07, 95% CI 0.89–1.29; P = 0.45), graft failure (RR 1.22, 95% CI 0.99–1.55; P = 0.07) and delayed graft function (RR 1.01, 95% CI 0.44–2.34; P = 0.98) were not significantly higher in renal transplant patients with SLE versus a control group. When the causes of graft failure were analysed in renal transplant patients with SLE versus without SLE, acute graft rejection (RR 1.20, 95% CI 0.98–1.47; P = 0.07), chronic graft rejection (RR 0.76, 95% CI 0.57–1.03; P = 0.08), graft thrombosis (RR 1.47, 95% CI 0.83–2.63; P = 0.19), recurrence of disease (RR 3.08, 95% CI 1.00–9.47; P = 0.05) and chronic allograft nephropathy (RR 1.08, 95% CI 0.60–1.95; P = 0.80) were also not significantly higher in patients with SLE. On the basis of the analysis, mortality from any cardiac cause (RR 0.82, 95% CI 0.67–1.01; P = 0.06), sepsis (RR 1.19, 95% CI 0.93–1.53; P = 0.17), malignancy (RR 0.79, 95% CI 0.51–1.24; P = 0.31) and cerebrovascular attack (RR 0.76, 95% CI 0.44–1.30; P = 0.31) were not significantly different in kidney transplantation patients with versus without SLE.ConclusionsComplications associated with kidney transplantation including mortality, graft failure and delayed graft function were not significantly higher in patients with SLE when compared with a control group. The causes of graft failure and mortality after kidney transplantation were also comparable in both groups. Therefore, kidney transplantation represents a promising treatment in patients with SLE with ESRD.

Buschke – Lowenstein Tumor. Case Report in a Patient with a History of Kidney Transplantation with Chronic Graft Rejection

Buschke-Lo wenstein tumor is a rare disease characterized by aggressive local infiltration in the perineal region, associated with human papillomavirus infection. It primarily affects immunocompromised patients, with surgical resection being the mainstay of treatment. We report the case of an adolescent with a history of chronic immunosuppression due to vasculitis and subsequent renal complications, including terminal chronic kidney disease and renal transplant failure. At 16 years old, she was diagnosed with Buschke-Lo wenstein tumor and underwent surgical treatment with complete lesion excision.

T cell-mediated rejection and cancer risk in 579,905 organ transplant recipients.

10552 Background: Prolonged immunosuppression following organ transplant raises post-transplant malignancy (PTM) risk without affecting chronic rejection graft failure (CRGF) rates. Our study investigated if T cell responses during rejection could protect against cancer, whereas T cell suppression in PTM might prevent rejection. Methods: Data from 1987 to 2023 on adult first-time single-organ transplant recipients were collected from the UNOS-OPTN database, excluding those with a history of malignancy. Time-dependent Cox regression and landmark analyses (at 1, 2, 3, 5, 10, 15, and 20 years) were used to explore the link between rejection-induced graft failure (RGF) and PTM. Results: The study included 579,905 recipients (kidney 386,878, liver 108,390, heart 45,046, lung 37,643, pancreas 1,948), with a mean follow-up of 7.3 years. RGF occurred in 9.5% of recipients (kidney 12.1%, liver 1.8%, heart 3.9%, lung 12.0%, pancreas 10.2%; p<0.001), with 2.1% experiencing acute rejection graft failure (ARGF) and 7.4%, CRGF. PTM occurred in 12.0% of recipients (kidney 9.9%, liver 12.4%. heart 20.9%, lung 22.6%, pancreas 11.3%; p<0.001), including breast (0.5%), digestive (1.2%), genitourinary (1.7%), gynecologic (0.1%), head and neck (0.3%), hematologic (1.4%), musculoskeletal (0.1%), neurologic (0.0%), respiratory (1.1%), and skin/Kaposi sarcoma (6.4%). In recipients with RGF, PTM risk significantly decreased (HR 0.21 [0.19-0.24]; p<0.001), with consistent trends observed across seven time landmarks (HR 0.20-0.07; p<0.001). Both ARGF and CRGF were associated with lower PTM risk (HR 0.23 [0.18-0.29], 0.21 [0.19-0.24]; p<0.001). In organ-specific analyses, kidney transplants showed similar outcomes for RGF, ARGF, and CRGF (HR 0.21-0.22; p<0.001). Lung transplants exhibited significant risk reductions with RGF (HR 0.44 [0.22-0.89]; p=0.02) and CRGF (HR 0.47 [0.24-0.94]; p=0.03), with no significant results in other organs. All findings remained consistent even after excluding re-transplantations and deaths due to rejection. Excluding PTM-related deaths from PTM cases significantly lowered RGF risk (HR 0.69 [0.65-0.73]; p<0.001), a trend that was consistent across all time landmarks (HR 0.51-0.80; p<0.001). This inverse pattern was seen in kidney, liver, heart, and lung transplants (HR 0.90 [0.84-0.95], 0.21 [0.11-0.38], 0.21 [0.14-0.31], 0.18 [0.14-0.23]; p<0.001) but not in pancreas transplants (HR 1.62 [0.69-3.77]; p=0.27). Conclusions: This study shows that rejection lowers cancer risk in kidney and lung transplants and that PTM reduces rejection risk in kidney, liver, heart, and lung transplants. Implementing enhanced cancer screening for those who have not experienced rejection may be considered. Further research is needed to elucidate the underlying T cell biology specific to each type of transplant.

Post liver transplant refractory dyslipidemia

ABSTRACT A 53-year-old male presented with intractable pruritus and jaundice. He underwent liver transplantation for liver cirrhosis a year prior to the current presentation. Post-transplantation, he developed diabetes mellitus. He experienced an episode of early acute graft rejection, 2 months after transplantation, which was successfully treated. Subsequently, about a year after transplantation, he developed chronic graft rejection. He was treated with everolimus and prednisolone. Incidentally, he was found to have elevated blood cholesterol, triglycerides, and low density lipoprotein (LDL) levels. The lipid levels were significantly higher than those commonly encountered in post-liver transplant patients. Dyslipidemia was treated with maximum dose of high-intensity statin, ezetimibe, and fenofibrate. However, there was not much reduction in lipid levels, indicating resistance to treatment. Subsequently, injection evolocumab 140 mg subcutaneously was added, administered once every 2 weeks. Following that, after only three doses of injection, there was about 65% reduction in the LDL level, which sustained at lower levels with continued treatment using evolocumab. Evolocumab was proven to be highly effective in reducing lipid levels in post-liver transplant patients who are refractory to treatment with conventional lipid-reducing medications.

Could the Cytomegalovirus Viral Load Be Correlated with Cellular Rejection in Asymptomatic Heart Transplant Recipients? A Brief Report

Abstract Introduction: Cytomegalovirus (CMV) infection is mainly associated with acute or chronic graft rejection in various solid organs. This study was conducted with the aim of evaluating the plasma viral load of CMV infection in postheart transplant patients and its correlation with the grading of cellular graft rejection in endomyocardial biopsies. Materials and Methods: In a cross-sectional study, 90 samples from 65 asymptomatic heart transplant recipients scheduled for routine endomyocardial biopsy were obtained. All the recipients had a history of positive serology for CMV infection before transplantation. Evaluation of their DNA was tracked using the polymerase chain reaction technique and the use of specific virus DNA primers, and based on this, the peak virus load (the number of virus copies per milliliter) was determined. A peak viral load >10,000 copies/mL was considered positive. Graft rejection grading was determined based on the ISHLT grading system. Results: The mean (standard deviation) age of the patients (37 men) was 67 (37.3) years. The graft rejection grading was as follows: 22.2% grade 0, 38.9% Quilty effect (QE), 35.6% grade 1, and 3.3% grade 2. The mean plasma viral load level of CMV infection was 2197.4 (1256.2) μg/μL, 1970.4 (1150.3) μg/μL, and 4567.2 (1669.1) μg/μL in grades 0, QE, and 1 and/or 2, respectively (P < 0.001). The virus load was significantly higher in those with higher grades of cellular rejection. Conclusion: The relationship between the plasma level of CMV viral load and the grading of cellular graft rejection in heart transplant patients could emphasize the role of CMV virus in the pathophysiology of graft rejection. A closer surveillance for CMV infection using the viral load is also recommended in particular in those who have higher grades of graft rejection.

Management of Kidney Transplant Outpatients With COVID-19: A Single Center Experience.

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56years), serum creatinine 127 (101-153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1-3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15-22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106-159) µmol/L post-COVID-19 infection and 128 (101-161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.

Diagnostic significance of TGF-β1 in kidney recipients with graft dysfunction

Development of minimally invasive diagnosis techniques for complications in recipients, based on analysis of the levels of molecular and genetic biomarkers, is an urgent task facing modern transplantology. Transforming growth factor beta 1 (TGF-β1), which has multiple effects in the body, among the potential indicators of complications.Objective: to assess the diagnostic significance of serum TGF-β1 in kidney recipients with graft dysfunction.Materials and methods. The study included 129 kidney recipients aged 17 to 68 years and 35 healthy subjects. Serum TGF-β1 levels in the recipients were determined by immunoenzyme technique.Results. Kidney recipients included 95 patients with laboratory and clinical signs of graft dysfunction, who underwent biopsy of the transplanted kidney, followed by morphological examination, and 34 recipients with normal graft function. Serum TGF-β1 levels in the kidney recipients were significantly higher than in their healthy counterparts (p = 0.00001); it did not correlate with most blood test parameters; with the glomerular filtration rate (GFR). Kidney recipients with graft dysfunction had significantly higher TGF-β1 levels than other recipients (p = 0.018). In recipients with graft dysfunction, morphological study revealed the following: acute tubular necrosis (ATN, n = 11), acute T-cell mediated rejection (ACR, n = 26), acute antibody-mediated rejection (AMR, n = 35), non-immune-mediated nephrosclerosis with signs of calcineurin inhibitor nephrotoxicity (CNI nephrotoxicity, n = 13), and recurrent glomerulonephritis (chronic graft rejection, n = 10). Recipients with immune-mediated graft injury (ACR, AMR and chronic rejection) had higher serum TGF-β1 levels than recipients with graft dysfunction resulting from other causes, p < 0.0001. Kidney recipients with serum TGF-β1 levels above the threshold value of 94.3 ng/mL had a higher risk of immune-mediated graft dysfunction than other kidney recipients (RR = 2.2 ± 0.22 [95% CI 1.46–3.46]) with 77.5% test sensitivity and 60.3% specificity.Conclusion. The calculated threshold serum TGF-β1 level in kidney recipients can be considered as an auxiliary indicator of graft dysfunction resulting from acute or chronic rejection.

Monocytic myeloid-derived suppressor cells mediate the resolution of lung ischemia-reperfusion injury via MerTK-dependent efferocytosis

Abstract Ischemia-reperfusion injury (IRI) after lung transplantation results in primary graft dysfunction leading to acute and chronic graft rejection. We investigated the role of monocytic myeloid-derived suppressor cells (M-MDSCs) to mediate inflammation-resolution of lung IRI. A murine model of lung hilar ligation was used in Balb/c (WT) and cebpβ −/−(M-MDSC deficient) mice. Lung function, inflammation and M-MDSC infiltration were assessed after 6- or 24hrs in mice undergoing sham control or IRI surgeries. CD11b +Ly6G −Ly6C +iNOS +M-MDSC lung infiltration in WT mice was significantly increased after 24hrs of IRI compared to 6hrs of IRI (9.9×10 3±1.2×10 3vs. 6.5×10 3±0.4×10 3; p=0.02; n=8/group), The upregulation of M-MDSC infiltration at 24hrs was accompanied by increased pulmonary compliance (5.3±0.2 vs. 2.9±0.1 μl/cm H 2O; p<0.0001; n=12/group), decreased neutrophil infiltration as well as decreased pro-inflammatory IL-17, TNF-α, and CXCL1 secretion compared to 6hrs of lung IRI. The resolution of lung IRI at 24hrs was blocked in cebpβ −/−mice compared to Balb/c mice as demonstrated by decreased pulmonary compliance (3.1±0.1 vs. 5.3±0.2 μl/cm H 2O; p<0.0001; n=7–12/group), that was accompanied by a decrease in M-MDSC lung infiltration (3.3×10 3±0.20×10 3vs. 9.9×10 3±1.2×10 3; p=0.003; n=5–8/group). In vitro analysis using a hypoxia-reoxygenation model of lung IRI displayed an increase in efferocytosis as shown by M-MDSC-dependent uptake of apoptotic neutrophils as well as alveolar epithelial cells via a MerTK-dependent mechanism, Collectively, our results indicate that lung IRI entails dysregulated inflammation-resolution which can be mitigated by M-MDSC-mediated MerTK-dependent efferocytosis.

Biostatistical Analysis of Relation between HLA-A/B and HLA-DR Eplet Mismatches and Renal Graft Outcome

Abstract: Despite all the clinical interventions that happened during the last 2 decades, the unavailability of a potent donor for renal transplantation remains a concern in the field of transplantation immunology. Recent studies promise the establishment of an effective clinical method to find a potent renal transplant donor, in the near future. Combining the use of molecular techniques with biostatistical methods can be a great tool for clinicians in choosing a potent donor. The present study was conducted from a cohort of 1144 (n=572 pair) renal transplant recipients and their donors to analyse eplet matches and mismatches. Initial observation of increased serum creatinine level which ranged from 2.0 to 21.0 mg/dL in patients treated for end-stage renal disease implied a single event of graft rejection. The statistical correlation between eplet mismatches and graft survival was observed to be significant with P value 0.003. A value of -0.215 at 0.01 significance showed the positive linear correlation between the increased numbers of HLA DR eplet mismatches towards chronic renal graft rejection. The correlation coefficient of -0.888 observed between the number of HLA DR eplet mismatches and days of graft survival clearly implies the effect of increased HLA DR eplet mismatch delayed graft rejection. The study gives an idea on the minimization of class II HLA DR eplet mismatches to decreased frequency of graft rejection as indicated by increased survival rate.

On indications for repeat liver transplantation

Objective: to study the causes of graft loss and indications for repeat liver transplantation (rLT).Materials and Methods. We studied the experience garnered from 250 orthotopic full-size cadaveric liver transplantations in 228 patients from 1998 to 2021. The severity of the patient’s condition at the time of intervention was estimated according to the MELD scale. Repeat surgeries were performed in 22 cases in 19 patients (analyzed group).Results. Organ preservation parameters, length of stay in intensive care unit (ICU), severity of postoperative complications in primary transplantations in general and in the analyzed group did not differ significantly. The main causes of graft loss were graft arterial insufficiency (57.9%) and hepatic artery thrombosis (21%). Severe early allograft dysfunction (EAD) and primary nonfunction accounted for 10.5%, portal vein thrombosis occurred in 5%, and chronic graft rejection was noted in 5% of cases.Conclusion. Arterial insufficiency is one of the leading causes of graft loss after liver transplantation. Early correction of arterial and biliary complications help in preserving graft viability.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.

Immunosuppressive drugs in renal transplantation

A kidney transplant, sometimes known as a renal transplant, is the treatment of choice for kidney failure at end stage renal disease (ESRD). The renal transplant surgery is followed by a lifetime course of immunosuppressive agents, divided into initial induction phase and later maintenance phase. It is seen that the risk of acute rejection is maximum in the initial months after transplantation (induction phase) and then reduces later (maintenance phase). In induction phase there is use of high-intensity immunosuppression immediately after transplantation, when the risk of rejection is maximum and then the dose reduced for long- term therapy. The main challenge in the renal transplantation community is long- term transplant survival. Long-term graft loss is mainly due to acute and chronic graft rejection, and also due to complications of immunosuppressive therapy. Currently, there is triple therapy as conventional immunosuppressive protocol: a calcineurin inhibitor, an antimetabolite agent, and a corticosteroid. The main aim of development of new immunosuppressive agents is not only improvement of short- term outcomes but also to increase the long- term graft survival by less nephrotoxicity, and minimal side-effects.

Expression of Class II Human Leukocyte Antigens on Human Endothelial Cells Shows High Interindividual and Intersubclass Heterogeneity.

Donor-specific antibodies against class II HLA are a major cause of chronic kidney graft rejection. Nonetheless, some patients presenting with these antibodies remain in stable histological and clinical condition. This study describes the use of endothelial colony-forming cell lines to test the hypothesis of the heterogeneous expression of HLA molecules on endothelial cells in humans. Flow cytometry and immunofluorescence staining revealed substantial interindividual and interlocus variability, with HLA-DQ the most variable. Our data suggest that the expression of HLA class II is predicted by locus. The measurement of endothelial expression of HLA class II in the graft could present a novel paradigm in the evaluation of the alloimmune risk in transplantation and certain diseases. HLA antigens are important targets of alloantibodies and allospecific T cells involved in graft rejection. Compared with research into understanding alloantibody development, little is known about the variability in expression of their ligands on endothelial cells. We hypothesized individual variability in the expression of HLA molecules. We generated endothelial colony forming cell lines from human peripheral blood mononuclear cells ( n =39). Flow cytometry and immunofluorescence staining were used to analyze the cells, and we assessed the relationship between HLA-DQ expression and genotype. Two cohorts of kidney transplant recipients were analyzed to correlate HLA-DQ mismatches with the extent of intragraft microvascular injury. Large variability was observed in the expression of HLA class II antigens, not only between individuals but also between subclasses. In particular, HLA-DQ antigens had a low and heterogeneous expression, ranging from 0% to 85% positive cells. On a within-patient basis, this expression was consistent between endothelial cell colonies and antigen-presenting cells. HLA-DQ5 and -DQ6 were associated with higher levels of expression, whereas HLA-DQ7, -DQ8, and -DQ9 with lower. HLA-DQ5 mismatches among kidney transplant recipients were associated with significant increase in graft microvascular. These data challenge the current paradigm that HLA antigens, in particular HLA class II, are a single genetic and post-translational entity. Understanding and assessing the variability in the expression of HLA antigens could have clinical monitoring and treatment applications in transplantation, autoimmune diseases, and oncology.

Protocol Biopsy After Kidney Transplant: Clinical Application and Efficacy to Detect Allograft Rejection.

Background Kidney transplant rejection is a major cause of graft dysfunction and failure. In recent years, there has been increased interest in renal allograft protocol biopsies to allow earlier detection of acute or chronic graft dysfunction or rejection to improve long-term graft survival and reduce graft failure. This study aimed to determine if renal allograft protocol biopsies performed within the first 12 months after transplantation help detect subclinical graft dysfunction or rejection. Methods We performed a retrospective analysis utilizing SUNY Upstate University Hospital data from January 2016 to March 2022 to assess transplant outcomes and biopsies. The study population was divided into two subgroups: non-protocol biopsies and protocol biopsies within the 12 months post-transplant. Results A total of 332 patients met our inclusion criteria and were included in the study. Patients were divided into two subgroups: 135 patients (40.6%) in the protocol biopsy group and 197 patients (59.4%) with non-protocol indication biopsies during the first year after the transplant. The overall number of rejection episodes reported was eight episodes (4.6%) in the protocol biopsy group and 56 episodes (18.3%) in the non-protocol indication biopsy group, which was significantly higher in the non-protocol biopsy group (P=0.001). Antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR) diagnoses were significantly higher in the non-protocol biopsy group (P=0.03 and P=0.03, respectively). We also mentioned a trend in terms of mixed antibody-mediated rejection and T-cell-mediated rejection diagnosis (P=0.07). One year after the rejection, the mean glomerular filtration rate(GFR) was 56.78 mL/min/1.73m2 in the protocol biopsy group and 49.14 mL/min/1.73m2 in the non-protocol indication biopsy group, and there was no significant difference anymore (P=0.11). The patient survival rate was not significantly higher in the protocol biopsy group compared to the non-protocol indication biopsy group (P=0.42). Conclusion This study suggests that performing protocol biopsies does not significantly benefit rejection rates, graft survival, or renal function within the first 12 months post-transplant. Given these results and the small but non-zero risk of complications associated with protocol biopsies, they should be reserved for those patients at high risk of rejection. It may be more feasible and beneficial to utilize less invasive tests, such as DSA and dd-cfDNA testing, for early diagnosis of a rejection episode.

Assessment of renal allograft rejection with diffusion tensor imaging.

To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Single-center experience of ex vivo lung perfusion and subsequent lung transplantation.

The safety of lung transplantation using ex vivo lung perfusion (EVLP) has been confirmed in multiple clinical studies; however, limited evidence is currently available regarding the potential effects of EVLP on posttransplant graft complications and survival with mid- to long-term follow-up. In this study, we reviewed our institutional data to better understand the impact of EVLP. Lungs placed on EVLP from 2014 through 2020 and transplant outcomes were retrospectively analyzed. Data were compared between lungs transplanted and declined after EVLP, between patients with severe primary graft dysfunction (PGD3) and no PGD3 after EVLP, and between matched patients with lungs transplanted with and without EVLP. In total, 98 EVLP cases were performed. Changes in metabolic indicators during EVLP were correlated with graft quality and transplantability, but not changes in physiological parameters. Among 58 transplanted lungs after EVLP, PGD3 at 72h occurred in 36.9% and was associated with preservation time, mechanical support prior to transplant, and intraoperative transfusion volume. Compared with patients without EVLP, patients who received lungs screened with EVLP had a higher incidence of PGD3 and longer ICU and hospital stays. Lung grafts placed on EVLP exhibited a significantly higher chance of developing airway anastomotic ischemic injury by 30days posttransplant. Acute and chronic graft rejection, pulmonary function, and posttransplant survival were not different between patients with lungs screened on EVLP versus lungs with no EVLP. EVLP use is associated with an increase of early posttransplant adverse events, but graft functional outcomes and patient survival are preserved.

Conversion to Belatacept in kidney transplant recipients with chronic antibody-mediated rejection (CAMR)

BackgroundThe costimulatory inhibitor Belatacept (Bela) has been shown to be an effective alternative in several clinical situations, including chronic antibody-mediated rejection, calcineurin toxicity, and de novo alloantibody formation. To further explore the usefulness of Belatacept under various clinical scenarios, we performed a retrospective analysis of a prospective database of all recipients who had a BPAR diagnosis of CAMR and were converted to a Belatacept maintenance immunosuppression regimen after kidney transplantation. Material and methodWe conducted a retrospective analysis of a prospectively collected database of all kidney transplants adult patients at SUNY Upstate Medical Hospital from 1 January 2013 to 31 December 2021. Our inclusion criteria were the patients who have been diagnosed with CAMR according to their renal biopsy based on the 2013 Banff criteria. The primary objective was to compare the kidney viability and function using GFR between the two interest groups and finally compare the outcomes. ResultsA total of 48 patients met our inclusion criteria based on the kidney biopsy result, which showed chronic antibody-mediated graft rejection (CAMR). Nineteen patients (39.6%) were converted to the Belatacept, and we continued the previous immunosuppression regimen in 29 patients (60.4%). The mean time from the transplant date to the diagnosis of CAMR was 1385 days in the Belatacept group and 914 days for the non-Belatacept group (P = 0.15). The mean GFR comparison at each time point between the groups did not show a significant difference, and Belatacept did not show superiority compared to the standard immunosuppression regimen in terms of kidney function preservation. 1 (5.2%) patient from the Belatacept group and 1 (3.4%) patient from the non-Belatacept group had a biopsy-proven acute rejection (BPAR) after CAMR confirmation, and it was comparable (P = 0.76). De novo synthesis of the DSA rate was 12.5% in the Belatacept group and 15% In the non-Belatacept group, which was comparable. (P = 0.90). The patient survival rate was 100% in both groups. ConclusionsWe conclude that compared to the standard Tacrolimus/MMF/Prednisone regimen, Belatacept did not significantly benefit in preserving the GFR in long-term follow-ups and stabilizing the DSA production, which is one of the main factors resulting in chronic graft failure.