Small Intestinal Complications of Intestinal Transplant-Associated Microangiopathy Post-stem Cell Transplantation.

We present the case of a patient who underwent human leukocyte antigen-haploidentical transplantation for T-cell acute lymphoblastic leukemia. Seven weeks after transplantation, the patient developed intestinal transplant-associated microangiopathy (iTAM). Although the iTAM was resolved temporarily, it recurred. Video capsule enteroscopy revealed multiple erosions and shallow ulcers in the jejunum and ileum. To the best of our knowledge, this is the first report to present images of possible small intestinal lesions in iTAM. The small intestinal mucosal images presented herein may potentially aid in the management of similar patients.

B-Cell Induction Therapies in Intestinal Transplantation.

Despite advancements in short-term outcomes since the inception of intestinal transplant, significant long-term graft failure persists. Early successes are attributed to the utilization of tacrolimus for maintenance therapy, coupled with T-cell modulating induction regimens, which effectively reduce the incidence of acute cellular rejection. However, the challenge of chronic allograft injury remains unresolved. There is increasing evidence indicating a correlation between donor-specific antibodies and the survival of visceral allografts. Strategies aimed at reducing the presence or load of these antibodies may potentially enhance long-term outcomes. Consequently, our focus is now turning toward B-cell induction therapies as a possible solution.

Intestinal Transplantation in the Developing World.

Intestinal failure (IF) remains as a life-threatening medical condition worldwide, but the disparity on the type and quality of medical care available, together with the different limitations to access among individual countries or regions, turned IF assessment and therapy into a difficult matter, which becomes a major hazard for the developing world. This article aims to provide an update regarding definitions used, the current general worldwide data, the developments, achievements, and the different access alternatives in Latin-America, Middle East, and Asia to exemplify what can be done to help patients with IF.

Intestinal Transplant for Hirschsprung's Disease: Stoma for Life or Not?

Hirschsprung's disease is a dysmotility disease caused by lack of ganglion cells in the bowel wall that can affect varying lengths of the intestine. In extreme circumstances, there can be little remaining ganglionated bowel, and the patient becomes dependent on parental nutrition (PN) for survival. Intestinal transplant has been utilized to salvage these patients suffering terminal complications of PN. The question as to whether to reestablish intestinal continuity, and thus not require a stoma is vexed. However, data and experience would suggest this can be safely done with good functional results.

Normothermic Preservation of the Intestinal Allograft.

Intestinal allotransplantation was first described in the 1960s and successfully performed in the 1980s. Since that time, less progress has been made in the preservation of the allograft before transplantation and static cold storage remains the current standard. Normothermic machine perfusion represents an opportunity to simultaneously preserve, assess, and recondition the organ for transplantation and improve the procurement radius for allografts. The substantial progress made in the field during the last 60 years, coupled with the success of the preclinical animal model of machine perfusion-preserved intestinal transplantation, suggest we are approaching the point of clinical application.

Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation.

BACKGROUND: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. METHODS: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated. RESULTS: The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%. CONCLUSIONS: This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

Clinical outcomes of intestinal transplant recipients receiving maintenance basiliximab, sublingual tacrolimus and prednisone: A case series.

INTRODUCTION: Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. METHODS: A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. RESULTS: A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. CONCLUSION: The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.

Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes.

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Nutrition support considerations in pediatric small bowel transplantation.

Enteral autonomy is the primary goal of intestinal failure therapy. Intestinal transplantation (ITx) is an option when enteral autonomy cannot be achieved and management complications become life-threatening. The purpose of this review is to summarize existing medical literature related to nutrition requirements, nutrition status, and nutrition support after pediatric ITx. Achieving or maintaining adequate growth after intestinal transplant in children can be challenging because of episodes of rejection that require the use of corticosteroids, occurrences of infection that require a reduction or discontinuation of enteral or parenteral support, and fat malabsorption caused by impaired lymphatic circulation. Nutrient requirements should be assessed and modified regularly based on nutrition status, growth, ventilatory status, wound healing, and the presence of complications. Parenteral nutrition (PN) should be initiated as a continuous infusion early postoperatively. Enteral support should be initiated after evidence of graft bowel function and in the absence of clinical complications. Foods high in simple carbohydrates should be limited, as consumption may result in osmotic diarrhea. Short-term use of a fat-free diet followed by a low-fat diet may reduce the risk of the development of chylous ascites. Micronutrient deficiencies and food allergies are common occurrences after pediatric ITx. Enteral/oral vitamin and mineral supplementation may be required after PN is weaned. Nutrition management of children after ITx can be challenging for all members of the healthcare team. Anthropometric parameters and micronutrient status should be monitored regularly so that interventions to promote growth and prevent or reverse nutrient deficiencies can be implemented promptly.

Fallo intestinal crónico secundario a síndrome de intestino corto: papel actual de la cirugía, la rehabilitación médica y el trasplante intestinal. Informe evolutivo a 16 años de manejo multidisciplinario / Chronic intestinal failure due to short bowel syndrome: current role of surgery, medical rehabilitation, and intestinal transplantation. A progress report after 16 years of multidisciplinary management

RESUMEN Antecedentes: la insuficiencia intestinal, en su grado más grave, se conoce como fallo intestinal crónico (FIC). Las últimas décadas han sido testigo de la incorporación, evolución y perfeccionamiento de tratamientos que, en su conjunto, se denominan rehabilitación intestinal y abarcan tanto procedimientos quirúrgicos como tratamientos médicos que, llevados a cabo por equipos multi e interdisciplinarios, alcanzan altas tasas de éxito. Objetivo: describir los resultados de 16 años en el tratamiento de pacientes con FIC secundario a síndrome de intestino corto (SIC), y la evolución del papel de la cirugía, la rehabilitación médica y el trasplante. Material y métodos: análisis retrospectivo de una base de datos prospectiva de pacientes con fallo intestinal crónico secundario a SIC entre febrero de 2006 y marzo de 2022. Resultados: se incluyeron 492 pacientes (368 adultos-A y 124 pediátricos-P). Grupo A: 111 pacientes recibieron cirugía de reconstrucción autóloga del tracto gastrointestinal (CRATGI), 16 péptido semisintético similar al glucagón de tipo 2 (sGLP-2); el 83% logró la rehabilitación, con un 77% de supervivencia a 10 años; el 6,8% (17 pacientes) requirió trasplante intestinal (TxI), con un 89% de independencia de la nutrición parenteral (NP) al año y supervivencia post-TxI del 29% a los 10 años. Grupo B: 18 recibieron CRATGI; 9, enteroplastia serial transversa (STEP); y 6, sGLP-2; el 52% se rehabilitó, con una supervivencia del 69% a los 10 años; 28 pacientes recibieron TxI, con 69% de independencia de nutrición parenteral (NP) al año y supervivencia del 39% a los 10 años. Conclusión: los resultados presentados resaltan el papel central de la cirugía y la rehabilitación médica para alcanzar la suficiencia intestinal.

ABSTRACT Background: Severe intestinal insufficiency is known as chronic intestinal failure (CIF). In recent decades, medical treatments and surgical procedures have been incorporated, developed and improved under the name intestinal rehabilitation. When performed by multiand interdisciplinary teams, these treatments have high success rates. Objective: The aim of present study is to describe the 16-year outcomes in the management of patients with CIF secondary to short bowel syndrome (SBS) and the role of surgery, medical rehabilitation, and transplantation. Material and methods: We conducted a retrospective analysis on a prospective database of patients treated with chronic intestinal failure due to SBS between February 2006 and March 2022. Results: A total of 492 patients (368 adults (Group A) and 124 pediatric patients (Group B)] were included. Group A: 111 patients underwent autologous gastrointestinal reconstruction surgery (AGIRS), 16 were treated with semisynthetic glucagon-like peptide-2 (sGLP2); 83% achieved rehabilitation, with 77% survival at 10 years; 6.8% (17 patients) required intestinal transplantation (ITx), with 89% independence from parenteral nutrition (PN) at 1 year and post-ITx survival of 29% at 10 years. Group B: 18 patients underwent AGIRS; 9 underwent serial transverse enteroplasty (STEP); and 6 received sGLP2; 52% were rehabilitated, with 69% survival at 10 years; 28 patients received ITx, with 69% independence from PN at 1 year and 39% survival at 10 years. Conclusion: These results highlight the central role of surgery and medical rehabilitation in the recovery of intestinal function.

Application of Intestinal Barrier Molecules in the Diagnosis of Acute Cellular Rejection After Intestinal Transplantation.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

Intestinal ultrasound may be a useful tool in monitoring acute rejection following intestinal transplantation.

BACKGROUND: Acute rejection is the leading cause of mortality and morbidity for children following intestinal transplantation. Rapid detection and prompt treatment are critical; however, the only reliable method of diagnosis and monitoring is endoscopic graft biopsies. The required regular anesthetics are particularly problematic in children, and non-invasive strategies are needed. METHODS: We describe the intestinal ultrasound findings of three children before and after treatment for rejection. Ultrasounds were performed within 24 h of endoscopically obtained biopsies which were used to establish a diagnosis of rejection and to define severity. A single sonographer performed the ultrasounds and was blinded to biopsy results at the time of the scanning. These findings are provided in the context of the ultrasound appearance of seven children who had no features of rejection on surveillance biopsies. RESULTS: Intestinal ultrasound demonstrated increased bowel wall thickness, vascularity, and mesenteric inflammation during moderate to severe rejection episodes. The submucosal layer was particularly thickened, which may represent a finding more specific for rejection. All patients demonstrated improvement in all quantitative ultrasound features correlating with the resolution of acute cellular rejection on histology. Patients with no evidence of rejection on biopsy had a bowel wall thickness range of 0.9-2.8 mm, suggesting a normal upper limit of 3 mm. CONCLUSION: Moderate and severe acute rejection may be detected and response to treatment can be monitored by intestinal ultrasound and, correlating with clinical improvement, can aid in follow-up.

Clinical characteristics and outcomes in CMV infection in intestinal transplant recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.

An analysis of the outcomes of Clostridioides difficile occurring in intestinal transplant recipients requiring hospitalization.

BACKGROUND: Organ transplantation is a known risk factor for Clostridioides difficile infection (CDI). There is limited published data on the impact of CDI in the intestinal transplant population. METHODS: We utilized the National Readmission Database (2010-2017) to study the outcomes of CDI in patients having a history of intestinal transplantation. Association of CDI with readmission and hospital resource utilization was computed in multivariable models adjusted for demographics and comorbidities. RESULTS: During 2010-2017, 8442 hospitalizations with the history of intestinal transplantation had indexed hospital admissions. Of these, 320 (3.8%) had CDI. CDI hospitalization in intestine transplant patients was associated with higher median cost $54 430 (IQR: 27 231, 109 980) as compared to patients who did not have CDI $48 888 (IQR: 22 578, 112 777), (ß: 71 814 95% confidence intervals [CI]: 676-142 953, p = .048). The median length of stay was also longer for patients with CDI 7 (IQR: 4, 13) days as compared to 5 (IQR: 3, 11) days in non-CDI (ß: 5.51 95% CI: 0.73-10.29, p = .02). The mortality rate, intestinal transplant complications, presence of malnutrition, acute kidney injury, ICU admissions, and sepsis were similar in both groups. CDI was the top cause of 30-day readmission in the intestinal transplant recipients with CDI during the index admission; the number of 30-day readmissions also increased from 2010 to 2017. CONCLUSION: CDI hospitalization in post-intestine transplant patients occurs commonly and is associated with a longer length of stay and higher costs during hospitalization. The CDI was the most common cause of readmission after the index admission of CDI in these patients.

The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function.

We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.

Pediatric intestinal transplantation.

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960's, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.

High-grade myelodysplastic syndrome in a pediatric multi-organ transplant recipient: A case report and literature review.

BACKGROUND: Pediatric myelodysplastic syndrome is a rare but life-threatening condition requiring prompt recognition and management. METHODS: We herein present the only reported case of a pediatric multi-organ transplant recipient developing myelodysplastic syndrome. RESULTS: The patient was a 14-year-old girl on chronic calcineurin inhibitor therapy who presented with peri-rectal pain approximately 13 years after liver, small bowel, and pancreas transplant. The initial workup revealed pancytopenia and parvovirus B19 viremia. Her definitive diagnosis was complicated by a lack of adequate bone marrow biopsy specimens and expert consultation that resulted in treatment for hemophagocytic lymphohistiocytosis. She was later diagnosed with high-grade myelodysplastic syndrome. Although curative treatment with chemotherapy and hematopoietic stem cell transplantation was strongly considered, it was not performed due to the child's rapid clinical progression, ventilator status, and active infections. The patient died approximately 6 months following symptom onset. CONCLUSIONS: This case emphasizes the importance of early recognition of myelodysplastic syndrome in multi-organ transplant recipients on chronic immunosuppression. Pancytopenia is a common presentation in the post-transplant period that requires thorough investigation. Multiple confounding considerations such as infection, immunosuppression, and systemic inflammation can delay the diagnosis of underlying hematological malignancies. Transplant care providers should be aware of myelodysplastic syndrome and advocate for a comprehensive evaluation, given early recognition and intervention can significantly improve outcomes.

Effect of a C5a receptor antagonist on macrophage function in an intestinal transplant rat model.

BACKGROUND: C5a promotes alloreactivity via the C5a receptor 1 (C5aR1) on immune cells, but this has not been confirmed in the case of small intestine transplantation immunity. In the present study, we examined the effect of C5aR1 antagonist (PMX53) on macrophage function in small intestinal transplantation. METHODS: The model was created by heterotopic intestinal transplantation using donor Dark Agouti and recipient Lewis rats. PMX53 was administered starting on the day of operation until postoperative day 7. The graft survivals were compared, and HE staining of grafts, lymphocyte mixed reaction test (MLR, mixed culture of T cells from lymph nodes and spleen cells from donors), and changes in macrophage and T cell accumulation in grafts on day 6 after transplantation were evaluated. In addition, the effect of PMX53 on macrophage differentiation and activation was assessed using macrophages derived from bone marrow (BMDM). RESULTS: Graft survival was significantly prolonged in the therapeutic group compared to the untreated group. Histological evaluation showed that PMX53 inhibited the shortening of the graft villus, and the stimulation index of MLR was significantly lower in the therapeutic group compared to the untreated group. In the therapeutic group, the accumulation of macrophages in intestinal graft and monocyte in blood were reduced, compared with the untreated group. PMX53 decreased the differentiation in BMDM and the mRNA expression of IL-1ß and TNF-α in activated BMDM. CONCLUSION: Inhibition of C5a/C5aR1 signaling appears to regulate macrophage differentiation and suppress rejection in small intestine transplantation immunity.

De novo lupus-like glomerulonephritis after pediatric non-kidney organ transplantation.

BACKGROUND: We propose a novel clinically significant finding, de novo lupus-like glomerulonephritis (DNLLGN), in patients with autoantibodies and kidney abnormalities in pediatric liver transplant (LT) and intestinal inclusive transplants (ITx). METHODS: We describe the clinical, serologic, and histopathologic presentation and kidney outcomes in eight patients from our center found to have DNLLGN on kidney biopsy. RESULTS: Pediatric recipients of non-kidney solid organ transplants developed an unusual de novo immune complex glomerulonephritis with morphologic similarity to lupus nephritis. Six had isolated LT (0.9% of all pediatric LT at our center) and two had ITx (2.1% of all ITx). Five (63%) presented with nephrotic syndrome. Five patients had autoantibodies. Patients underwent kidney biopsy at a mean of 11.5 years in LT and 2.8 years in ITx after the index transplant. Biopsies demonstrated changes similar to focal or diffuse active lupus. Follow-up eGFR at a mean of 6 years after biopsy showed a mean decrease of 30 ml/min/1.73 m2 in all patients (p = 0.11). CONCLUSIONS: DNLLGN has not been previously recognized in this clinical setting, yet 8 kidney biopsies from pediatric recipients of LT and ITx at our center in 25 years demonstrated this finding. DNLLGN appears to be an under-reported phenomenon of clinical significance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Late Bleeding Episodes Following Intestinal Transplantation: It Is Not Always Rejection or Infection.

Ectopic varices have been reported in 5% of children presenting with variceal bleeding and are defined as portosystemic venous collaterals occurring anywhere in the abdomen except in the cardioesophageal region. The liver-intestinal transplant or isolated liver-intestinal transplant patient presenting several years post-transplant with ectopic variceal bleeding as a consequence of portal hypertension is a seldom reported complication. Etiologies such as rejection or infection are a more common source of bleeding, and only after excluding these can differentials such as portal hypertension secondary to a blocked portacaval shunt or native liver disease be considered.