Antibody-mediated rejection of the kidney after simultaneous pancreas-kidney transplantation.

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (

Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection.

Commonly available clinical parameters fail to predict early acute cellular rejection (EAR, occurring within 6 months after transplant), a major risk factor for graft loss after kidney transplantation. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective cohort study (Genomics of Chronic Allograft Rejection [GoCAR]) and evaluated the relationship of pretransplant transcriptomic profiles with EAR. EAR was associated with downregulation of NK and CD8+ T cell gene signatures in pretransplant blood. We identified a 23-gene set that predicted EAR in the discovery (n = 81, and AUC = 0.80) and validation (n = 74, and AUC = 0.74) sets. Exclusion of recipients with 5 or 6 HLA donor mismatches increased the AUC to 0.89. The risk score derived from the gene set was also significantly associated with acute cellular rejection after 6 months, antibody-mediated rejection and/or de novo donor-specific antibodies, and graft loss in a cohort of 154 patients, combining the validation set and additional GoCAR patients with surveillance biopsies between 6 and 24 months (n = 80) posttransplant. This 23-gene set is a potentially important new tool for determination of the recipient's immunological risk before kidney transplantation, and facilitation of an individualized approach to immunosuppressive therapy.

Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.

BACKGROUND: An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab. METHODS: To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64). RESULTS: Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios. CONCLUSIONS: In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.

Defining the phenotype of antibody-mediated rejection in kidney transplantation: Advances in diagnosis of antibody injury.

The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause). In this article we review not only the ABMR phenotypes acknowledged in the most recent Banff classification, but also the phenotypes related to novel pathogenic antibodies (non-HLA DSA, antibody isoforms and subclasses, complement-binding functionality) and molecular diagnostic tools (gene transcripts, metabolites, small proteins, cytokines, and donor-derived cell-free DNA). These novel tools are also being considered for the prognosis and monitoring of treatment response. We propose that improved classification of ABMR based on underlying pathogenic mechanisms and outcomes will be an important step in identifying patient-centered therapies to extend graft survival.

High-dose mycophenolate mofetil in the treatment of posttransplant glomerular disease in the allograft: a case series.

BACKGROUND: Glomerular disease is an important cause of allograft loss. Treatment regimens for posttransplant glomerular disease are not well defined. Several reports have demonstrated that mycophenolate mofetil (MMF) is effective in treating native kidney glomerular disease. The effects of MMF are dose related. Therefore, we hypothesized that high-dose MMF (3 g/day) would be effective in treating glomerular disease in the allograft, minimizing the need for intravenous steroids and/or cyclophosphamide. This case series describes the results of the use of high-dose MMF in 6 patients. METHODS: High-dose MMF (3 g/day) was used to treat biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, proliferative lupus nephritis, and perinuclear antineutrophil cytoplasmic antibodies glomerulonephritis) in 6 renal transplant recipients. Patients were offered this treatment if they had failed or did not tolerate standard treatment regimens. Remission was defined by a decrease or stabilization of serum creatinine, decrease in proteinuria and, where applicable, improvement in immunological markers of disease. RESULTS: All 6 patients had disease remission after starting MMF with the most common side effect being leukopenia, which responded to dose reduction. CONCLUSIONS: High-dose MMF may be an effective agent in treating glomerular disease in the allograft.

Combined percutaneous mechanical and chemical thrombectomy for renal vein thrombosis in kidney transplant recipients.

Renal vein thrombosis occurring after the immediate post-transplant period often leads to loss of the transplant organ. We report two cases of renal vein thrombosis in the setting of de novo membranous nephropathy occurring 5 and 26 months post-transplantation. Both cases were treated with percutaneous mechanical thrombectomy and localized catheter-directed thrombolysis with resolution of clot burden, and regained kidney function after thrombolysis without subsequent thromboses. Percutaneous mechanical thrombolysis can be safely done in renal transplant recipients and should be considered in patients with renal vein thrombosis beyond the immediate post-operative period in order to minimize exposure to systemic thrombolysis.

West Nile virus encephalitis in a kidney transplant recipient.

We describe a case of West Nile virus encephalitis in a 54-year-old kidney transplant recipient. The clinical course was rapid and fatal. Serial CSF samples showed an evolving mononuclear pleiocytosis and serial MRIs showed increasing signs of cytotoxic edema in her basal ganglia. Seroepidemiological testing indicated that the infection was most likely acquired from transfusion of fresh frozen plasma at the time of transplantation.