Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis.

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

ABO-incompatible living-donor kidney transplantation: Study of 48 patients after desensitisation. / Trasplante renal de donante vivo ABO incompatible. Estudio de 48 pacientes tras desensibilización.

BACKGROUND: ABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes. OBJECTIVE: Our aim was to show the results obtained with this technique in our hospital. METHODS: Forty-eight patients with a mean age of 50.9±10.9 years were included. Follow-up was 44.6±30.9 months. Conditioning: rituximab 375mg/m2, tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titres for transplantation:<1:8. RESULTS: Pre-process IgG titre 1:124±1:140, IgM titre 1:77±1:55. After 6±3 sessions, IgG decreased to<1:8 in 47 patients and to<1:16 in one. IgM was<1:8 in all cases. Twenty-four patients (50%) had haematoma, 7 re-intervention (14.6%), 29 (60%) required transfusion. At 5 years, acute rejection had occurred in 5 cases (8.7%), CMV infection in 9 (19.7%), BK viraemia in 5 (12.4%), post-transplant diabetes in 10 (23.4%) and lymphocele in 3 (6.4%). Patient survival was 97.1% at 5 years and graft survival 95.7% at one year and 93% at 5 years. Causes of graft loss: thrombosis (n=1); mixed rejection (n=1); and death (n=2). Serum creatinine levels were 1.4±0.4mg/dl at one and 3 years and 1.3±0.3mg/dl at 5 years. Proteinuria was 0.2±0.2g/24h at one, 3 and 5 years. CONCLUSIONS: ABO-incompatible living-donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes. There is a low incidence of acute rejection and no increase in infectious complications. An increased tendency for postoperative bleeding was found.

Correlation between glycemic control and the incidence of peritoneal and catheter tunnel and exit-site infections in diabetic patients undergoing peritoneal dialysis.

BACKGROUND: Diabetes mellitus, especially if complicated by poor glycemic control, portends an increased risk of infection. The significance of this association in the case of diabetic patients undergoing peritoneal dialysis (PD) has not been assessed. METHODS: Using a retrospective observational design, we analyzed the association between glycemic control at the start of PD (estimated from glycosylated hemoglobin levels) and the risk of peritoneal and catheter tunnel and exit-site infections during follow-up in 183 incident patients on PD. We used the median value of glycosylated hemoglobin to classify patients into good (group A) or poor (group B) glycemic control groups. We applied multivariate strategies of analysis to control for other potential predictors of PD-related infection. RESULTS: Groups A and B differed significantly in age, dialysis vintage, use of insulin, and rate of Staphylococcus aureus carriage. Neither the incidence (0.60 episodes in group A vs 0.56 episodes in group B per patient-year) nor the time to a first peritoneal infection (median: 42 months vs 38 months) differed significantly between the study groups. In contrast, group B had a significantly higher incidence of catheter tunnel and exit-site infections (0.23 episodes vs 0.12 episodes per patient-year) and shorter time to a first infection episode (64 months vs 76 months, p = 0.004). The difference persisted in multivariate analysis (adjusted hazard ratio: 2.65; 95% confidence interval: 1.13 to 6.05; p = 0.013). We observed no differences between the study groups in the spectrum of causative organisms or in the outcomes of PD-related infections. CONCLUSIONS: Poor glycemic control is a consistent predictor of subsequent risk of catheter tunnel and exit-site infection, but not of peritoneal infection, among diabetic patients starting PD therapy.