Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.

Anticoagulant-related nephropathy (ARN) classically presents with hematuria followed by acute kidney injury (AKI) during a period of overanticoagulation with supratherapeutic international normalized ratio (INR). The corresponding renal histology is acute tubular injury (ATI) associated with red blood cells (RBCs) within the Bowman space and obstructive tubular RBC casts.1 It has been observed that ARN is more common among patients with chronic kidney disease (CKD), and it was shown to accelerate CKD progression and increase mortality.

A case of transfusion-dependent anemia in a simultaneous pancreas and kidney (SPK) transplant recipient that masqueraded as gastrointestinal bleeding (GIB) is described. The anemia was attributed to bleeding from the donor duodenal cuff based on balloon enteroscopy findings. The patient underwent multiple contrast-enhanced computed tomography scans and multiple endoscopies with confounding features until, eventually, the diagnosis was established. We discuss the diagnostic difficulties and the therapeutic dilemma, along with the pitfalls in ascertaining the final diagnosis.

Faecal Microbiota Transplantation (FMT) is widely utilised for recurrent Clostridioides difficile infection. Use of FMT for the intestinal eradication of multidrug-resistant organisms (MDROs) has been described in the literature with decolonisation rates from 37.5% to 87.5%. We perform FMT via naso-gastric tube using donor stool prepared anaerobically, using prevention of invasive disease as an endpoint. FMT was considered for either; 1) Patients who were colonised with >1 MDRO (carbapenem-resistant Enterobacteriaceae, vancomycin resistant Enterococci or extended-spectrum beta lactamase (ESBL) and at risk of invasive MDRO disease or 2) patients who had recurrent MDRO-mediated invasive disease. Sixteen MDRO colonised/infected patients underwent FMT. Nine patients had a haematological disorder. Eight of these patients had had prolonged admissions (range 6-20 weeks) complicated by septic episodes (5/9 had a MDR bacteraemia) pre-FMT. Post FMT all patients had shorter admissions including five who received higher intensity immunosuppression. Only 1/9 developed MDRO-mediated invasive disease. Seven FMT patients had recurrent ESBL urinary tract infections (UTIs). 4/7 were renal transplant patients. Following FMT the 3 non-transplant patients had no further UTIs up to six month period. Four transplant patients had reduced number of infections, admissions and use of antibiotics. 5/13 (39%) patients were not MDRO colonised on rectal screens post-FMT (follow up range 12 weeks – 24 months). Although decolonisation rates were low, patient outcomes post-FMT were apparently improved. Mechanisms of FMT have not fully been established, improvement of colonisation resistance by restoration of microbiota composition or functionality in at risk groups could be more important than intestinal eradication.

BACKGROUND Pancreas transplantation has proven to be the most effective therapeutic option for insulin-dependent diabetes mellitus. However, despite advances in surgical technique and continuously improving outcomes, pancreas transplantation has the highest complication rate among all solid-organ transplants. Vascular complications in particular can be catastrophic, with graft- and life-threatening potential. Ectopic variceal bleeding is less common and is rarely reported in the literature. CASE REPORT A 51-year-old man presented with recurrent intermittent gastrointestinal bleeding (GIB) associated with hepatic dysfunction and portal hypertension 4 years after a successful pancreas-after-kidney transplant. Apart from positive serology for hepatitis E virus, all the other liver disease screening results were negative. He was extensively investigated with 6 computed tomography (CT) scans, 3 esophago-gastro-duodenoscopies (EGD), 3 colonoscopies, and 1 visceral arteriogram before the plausible diagnosis of ectopic trans-anastomotic variceal bleeding involving the pancreas transplant was established. Selective variceal catheterization and embolization were done with 3% sodium tetradecyl sulphate (STD). He remained free of bleeding after embolization. CONCLUSIONS This case report adds to the scanty literature on the management of ectopic variceal bleeding in a pancreas transplant recipient. Diagnosis of ectopic varix is usually challenging and frequently requires a visceral arteriogram. We describe a novel minimally-interventional technique to obtain source control and also discuss the complexity involved in the management, along with future implications.

De novo HLA donor-specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyze the development of HLA transfusion-specific antibodies (TSA) to blood donors of transfusions given posttransplant and examine the impact on clinical outcomes. A total of 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244 (61.5%) blood donors. In 70/150 (46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+ = TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+ = TSA+ patients had increased risk of allograft failure (P = .0025) and AMR (P = .02) compared with the DSA+ ≠ TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes.

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re‐transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX−, n = 48). Sera were assessed for HLA‐A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non‐DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NX− group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut‐off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NX− group. Nephrectomy is followed by the long‐term production of DSA and non‐DSA HLA antibodies and negatively impacts on the chances of finding a HLA‐compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re‐transplantation in the NX− group.

Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial.

BACKGROUND:Patients who require acute initiation of dialysis have higher mortality rates when compared with patients with planned starts. Our primary objective was to explore the reasons and risk factors for acute initiation of renal replacement therapy (RRT) among patients with end-stage kidney disease (ESKD). Our secondary objective was to determine the difference in glomerular filtration rate (GFR) change in the year preceding RRT between elective and acute dialysis starts. METHODS:We conducted a single-centre retrospective observational study. ESKD patients either started dialysis electively (planned starters) or acutely and were known to renal services for >90 (unplanned starters) or <90 days (urgent starters). RESULTS:In all, 825 consecutive patients initiated dialysis between January 2013 and December 2015. Of these, 410 (49.7%) patients had a planned start. A total of 415 (50.3%) patients had an acute start on dialysis: 244 (58.8%) unplanned and 171 (41.2%) urgent. The reasons for acute dialysis initiation included acute illness (58%) and unexplained decline to ESKD (33%). Cardiovascular disease [n = 30 (22%)] and sepsis [n = 65 (48%)] accounted for the majority of acute systemic illness. Age and premorbid cardiovascular disease were independent risk factors for acute systemic illness among unplanned starts, whereas autoimmune disease accounted for the majority of urgent starts. The rate of decline in GFR was greater in the month preceding RRT among acute dialysis starters compared with planned starters (P < 0.001). CONCLUSIONS:Cardiovascular disease and advancing age were independent risk factors for emergency dialysis initiation among patients known to renal services for >3 months. The rapid and often unpredictable loss of renal function in the context of acute systemic illness poses a challenge to averting emergency dialysis start.