Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.

While the guidelines for vaccination in renal transplant recipients recommend the use of pneumococcal polysaccharide (PPS) and tetanus toxoid (TT), their efficacy in immunocompromised renal transplant recipients is not known. Here we tested the effect of everolimus on immune responses after vaccination by measuring the capacity of 36 stable renal transplant recipients to mount cellular and humoral responses after vaccination. Twelve patients in each treatment arm received immunosuppressive therapy consisting of prednisolone (P) plus cyclosporine (CsA), mycophenolate sodium (MPA), or everolimus. Patients were vaccinated with the T-cell-dependent antigens immunocyanin and TT, and the T-cell-independent PPS. Treatment with CsA partially inhibited and MPA completely abolished the capacity to mount a primary humoral response, whereas everolimus left this largely intact. Recall responses were inhibited by MPA only. All drug combinations inhibited cellular responses against TT. In patients treated with MPA, B-cell numbers were severely reduced. Thus, combined with P, treatment with MPA completely disturbed primary and secondary humoral responses. Everolimus or CsA allowed the boosting of T-cell-dependent and -independent secondary humoral responses. Treatment with everolimus allowed a primary response.

A significant correlation was observed between interstitial infiltrates of CD20+ cells and CD3+ cells (r=0.720, P<0.001) suggesting that if B-cell infiltrates are present during rejection, they occur with T-cell infiltrates in a concurrent fashion. In contrast to previous reports, no relation was found between the number of CD20+ cells, in aggregates or in a scattered interstitial pattern, and response to conventional therapy. Remarkably, CD3+T cell aggregates did predict a favorable renal outcome.

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We observed a significant increase in (CMV-specific) effector-type CD8 and CD4 T-cell counts in everolimus-treated patients. These findings may at least in part explain the reported low incidence of CMV-related pathology in everolimus-treated patients.

Summary Phenotypic characterization of T and B lymphocytes allows the discrimination of functionally different subsets. Here, we questioned whether changes in peripheral lymphocyte subset distribution reflect specific clinical and histopathological entities after renal transplantation. Sixty‐five renal transplant recipients with either histologically proven (sub)clinical acute rejection or chronic allograft dysfunction, or without abnormalities were studied for their peripheral lymphocyte subset composition and compared with 15 healthy control individuals. Naive, memory and effector CD8+ T‐cell counts were measured by staining for CD27, CD28 and CD45RO/RA. In addition, we studied the CD25+ CD4+ T‐cell population for its composition regarding regulatory Foxp3+ CD45RO+ CD127– cells and activated CD45RO+ CD127+ cells. Naive, non‐switched and switched memory B cells were defined by staining for IgD and CD27. We found a severe decrease in circulating effector‐type CD8+ T cells in recipients with chronic allograft dysfunction at 5 years after transplantation. Percentages of circulating CD25+ CD127low CD4+ regulatory T cells after transplantation were reduced, but we could not detect any change in the percentage of CD127+ CD45RO+ CD4+ activated T cells in patients at any time or condition after renal transplantation. Regardless of clinical events, all renal transplant recipients showed decreased total B‐cell counts and a more differentiated circulating B‐cell pool than healthy individuals. The changes in lymphocyte subset distribution probably reflect the chronic antigenic stimulation that occurs in these transplant recipients. To determine the usefulness of lymphocyte subset‐typing in clinical practice, large cohort studies are necessary.

Introduction: The incidence of urological complications after renal transplantation ranges from 2.5 to 30%. Often surgical revision is necessary. The risk factors for surgical revision and which surgical techniques to apply are not elucidated. This study investigates the outcome and risk factors for surgical revision of the ureterocystostomy. Materials and Methods: Between January 1995 and March 2009, 1,157 consecutive kidney transplantations were performed. All patient charts and surgical reports were reviewed. Results: Urological complications occurred in 142 (12.3%) patients. In 60 patients (5.2%) surgical revision was necessary. Of these 60 patients, 43 (71.7%) received neoureterocystostomy, 10 (16.7%) ureteropyelostomy reconstruction and 7 (11.7%) other techniques. Independent risk factors for surgical revision were donor ureteral reconstruction (odds ratio (OR) 48.66, 95% confidence interval (CI) 5.01–472.97), recipient age <18 years (OR 4.85, 95% CI 1.50–15.72) and delayed graft function (OR 2.70, 95% CI 1.36–5.36). Ureteral stenting was a protective factor for surgical revision (OR 0.30, 95% CI 0.12–0.81). The urological complication rates after neoureterocystostomy, ureteropyelostomy reconstruction and other techniques were 16, 0 and 0%, respectively. The overall surgical success rate was 92%. Conclusions: Ureteral stenting, recipient age, delayed graft function and perioperative ureteral reconstruction are significant factors associated with surgical revision of the ureterocystostomy. Surgical revision of the ureterocystostomy is a successful therapy with a low recurrence rate.

Summary Interleukin‐17 (IL‐17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL‐17 in transplantation. Our study investigated whether quantifying IL‐17+ cells in renal transplant biopsies during acute rejection could have additional prognostic value for better stratifying patients at risk for nonresponsiveness to anti‐rejection therapy and future graft dysfunction. Forty‐nine renal biopsies with acute rejection were double immunostained and quantitatively analyzed for IL‐17 and CD3 (IL‐17+ T‐lymphocytes), tryptase (IL‐17+ mast cells) or CD15 (IL‐17+ neutrophils). Total IL‐17+ cell count correlated with total percentage of inflamed biopsy and estimated GFR during rejection. Most IL‐17+ cells were mast cells and neutrophils. We could hardly find any IL‐17+ T‐lymphocytes. IL‐17+ mast cells correlated with interstitial fibrosis/tubular atrophy (IF/TA). None of the IL‐17+ cell counts had an additional prognostic value for response to anti‐rejection treatment. Multivariate analysis correcting for C4d positivity and time from transplantation to biopsy showed that total IL‐17+ cell count independently predicts graft dysfunction at the last follow‐up, which was validated in an independent cohort of 48 renal biopsies with acute rejection. We conclude that intragraft IL‐17+ cell count during acute allograft rejection could have an additional value for predicting late graft dysfunction.