DQ DSAbs are associated with inferior allograft outcomes. This study shows the importance of establishing the DQ match before transplantation to define immunologic risk.

This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.

In renal transplant patients with de novo donorspecific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-

We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell-dependent allo-specific reactivity was shown by depletion of CD25(+) cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19(+) cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.

Background and objectives Venous thromboembolism (VTE) occurs in 7%-40% of nephrotic patients. The risk of VTE depends on the severity and underlying cause of nephrotic syndrome. This study investigated the use of low-dose prophylactic anticoagulation to prevent VTE in patients with nephrotic syndrome caused by primary glomerulonephritis.Design, setting, participants, & measurements Since 2006, all patients presenting with nephrotic syndrome to Imperial College Kidney and Transplant Centre have been considered for treatment with a novel anticoagulation prophylaxis regimen. All cases of nephrotic syndrome secondary to primary membranous nephropathy, minimal-change disease, and FSGS over a 5-year period were retrospectively reviewed. Patients with serum albumin,2.0 g/dl received prophylactic-dose low-molecular-weight heparin or low-dose warfarin; patients with albumin levels of 2.0-3.0 g/dl received aspirin, 75 mg once daily. All thrombotic events and bleeding complications were recorded.Results A total of 143 patients received the prophylactic anticoagulation regimen. Median follow-up was 154 weeks (range, 30-298 weeks). The cohort had features associated with a high risk of developing VTE; 40% of the cohort had an underlying diagnosis of membranous nephropathy, and the initial median serum albumin was 1.5 g/dl (range, 0.5-2.9 g/dl). No VTE occurred in patients established on prophylaxis for at least 1 week. VTE was diagnosed in 2 of 143 patients (1.39%) within the first week after presentation and starting prophylaxis. In both cases, it is unclear whether the thrombus had developed before or after the start of prophylaxis. One of 143 (0.69%) patients receiving prophylaxis was admitted urgently with gastrointestinal hemorrhage. Two of 143 patients (1.40%) had elective blood transfusions and procedures to manage occult gastrointestinal bleeding. No other bleeding events occurred in patients receiving prophylaxis.Conclusions This regimen of prophylactic antiplatelet or anticoagulant therapy appears effective in preventing VTE in nephrotic syndrome, with relatively few hemorrhagic complications.

Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.

Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.

It has been shown that low-level preformed donorspecific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. The relevance of preformed DSAbs in patients receiving alemtuzumab induction and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p = 0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibodymediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive regime incorporating alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.