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Insufficient hemodynamics during agonal phase-i.e. the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2>60% or SpO2 80 mmHg or SBP

In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor-specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.

This review gives an outline of the indications for faecal microbiota transplantation (FMT) for diseases other than Clostridium difficile (C. difficile) infection. The remarkable efficacy of FMT against C. difficile infection has already been demonstrated. The use of FMT for other diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and metabolic syndrome, is now being evaluated. The currently available data suggest that FMT might be beneficial for IBD (including ulcerative colitis and, to some extent, Crohn's disease), IBS, and insulin resistance. Several randomized clinical trials are currently being performed, and data are eagerly awaited. A new field of research for the implementation of FMT is the eradication of pathogenic and multiresistant enteric microorganisms. A few animal studies have been performed within this field, but hardly any research data from human studies are available at present.

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time. (C) 2014 Published by Elsevier B.V.

T cells play a dual role in transplantation: They mediate transplant rejection and are crucial for virus control. Memory T cells generated in response to pathogens can cross-react to alloantigen, a phenomenon called heterologous immunity. Virus-specific CD8+ T cells cross-reacting to donor-alloantigen might affect alloimmune responses and hamper tolerance induction following transplantation. Here, we longitudinally studied these cross-reactive cells in peripheral blood of 25 kidney transplant recipients with a cytomegalovirus and/or Epstein-Barr virus infection. Cross-reactive T cells were identified by flow cytometry as virus-specific T cells that proliferate in response to donor cells in a mixed-lymphocyte reaction. In 13 of 25 patients, we found cross-reactivity to donor cells for at least 1 viral epitope before (n = 7) and/or after transplantation (n = 8). Cross-reactive T cells were transiently present in the circulation, and their precursor frequency did not increase following transplantation or viral infection. Cross-reactive T cells expressed interferon-γ and CD107a in response to both alloantigen and viral peptide and resembled virus-specific T cells in phenotype and function. Their presence was not associated with impaired renal function, proteinuria, or rejection. In conclusion, virus-specific T cells that cross-react to donor-alloantigen are transiently detectable in the circulation of kidney transplant recipients.

Summary Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4+ T cells remain depleted for up to 2 years, whereas the CD8+ T cell compartment is refilled rapidly by highly differentiated CD27–CD45RA+CD57+effector-type cells. Because the presence of these highly differentiated CD8+ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV+) to that in three CMV+ patients without reactivation (non-reactivating CMV+), and to that in three CMV-seronegative recipients receiving a kidney from a CMV-seronegative donor (CMV−/−). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8+ T cells were determined. In reactivating CMV+ patients, total CD8+ T cells reappeared rapidly, whereas in non-reactivating CMV+ patients they lagged behind. In CMV−/− patients, CD8+ T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8+ T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8+ T cells showed increased skewing in their Vβ repertoire in both CMV−/− and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.

Summary Several assays to measure pre-existing allospecific T cell immunity in renal transplant candidates have been developed in the past years. In 46 patients, we used flow cytometry-based mixed lymphocyte culture to measure the precursor frequency and phenotype of alloreactive T cells before renal transplantation, using donor-specific or third-party cells for allostimulation. Allostimulation induced up-regulation of co-stimulatory molecules, chemokine receptors relevant for migration of T cells into the graft and effector proteins. Recipients prone for acute rejection had a higher precursor frequency of alloreactive CD8+ T cells and a lower percentage of interleukin (IL)-7Rα expressing alloreactive CD8+ T cells than non-rejectors. These data point to quantitative and qualitative differences between T cells of patients who will experience acute cellular rejection episodes from those who will not.

Donor-specific antibodies (DSA) form a significant barrier in solid organ transplantation of highly pre-sensitized candidates. Although avoiding transplantation over a positive cross-match test can largely prevent the occurrence of hyperacute antibody-mediated rejection, transplantation of highly pre-sensitized candidates is often complicated by the occurrence of acute and chronic antibody-mediated graft rejection leading to diminished graft function and survival. The pre-existent HLA and/or non-HLA-specific antibodies are without any doubt important contributing factors underlying humoral-mediated graft injury. Furthermore, increasing evidence underlines the association of newly formed de novo DSA after transplantation with poor graft function and survival. There is still a need to further develop desensitizing therapies not only to make transplantation of highly pre-sensitized candidates feasible, but also to reduce the new formation of allo-antibodies. Here, we summarize current views on desensitization therapies and the impact of the presence of DSA on the fate of the kidney graft.

Summary Cyclopentenyl cytosine (CPEC) has been shown to induce apoptosis in human T lymphoblastic cell lines and T cells from leukaemia patients. In this study we have addressed the question of whether CPEC is able to decrease proliferation and effector functions of human alloresponsive T lymphocytes and induce T cell anergy. The proliferative capacity of human peripheral blood mononuclear cells in response to allogeneic stimulation was measured by 5,6-carboxy-succinimidyl-diacetate-fluorescein-ester staining. Flow cytometric analysis was performed using surface CD4, CD8, CD25, CD103 and intracellular perforin, granzyme A, granzyme B, caspase-3 and forkhead box P3 (FoxP3) markers. The in vivo immunosuppressive capacity was tested in a murine skin graft model. Addition of CPEC at a concentration of 20 nM strongly decreased the expansion and cytotoxicity of alloreactive T cells. Specific restimulation in the absence of CPEC showed that the cells became anergic. The drug induced caspase-dependent apoptosis of alloreactive T lymphocytes. Finally, CPEC increased the percentage of CD25high FoxP3+ CD4+ and CD103+ CD8+ T cells, and potentiated the effect of rapamycin in increasing the numbers of alloreactive regulatory T cells. Treatment with CPEC of CBA/CA mice transplanted with B10/Br skin grafts significantly prolonged graft survival. We conclude that CPEC inhibits proliferation and cytotoxicity of human alloreactive T cells and induces alloantigen non-responsiveness in vitro.

BACKGROUND The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function. METHODS Retrospective cohort study in adult renal allograft recipients with 1-year follow-up after transplantation (Tx). Renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease formula) and 24-h urine protein excretion. RESULTS A total of 431 renal allograft recipients were analyzed; 57 (13.2%) developed AGPN within 1 year after Tx. Median time between Tx and AGPN was 50 days. Risk factors for AGPN were the presence of a urological catheter (odds ratio [OR] = 18.93, 95% confidence interval [CI] = 8.00-44.81, P < 0.001) and preceding asymptomatic bacteriuria (ASB) (OR = 2.16, 95% CI = 1.20-3.90, P = 0.009). In 72.7%, the causative microorganism of ASB was identical to that of the succeeding AGPN episode. Multivariable linear regression analysis showed that experiencing AGPN did not decrease the eGFR (P = 0.61) nor did increased proteinuria (P = 0.29) 1 year after Tx. For the eGFR, an interaction was found between AGPN/bacteriuria (BU) and acute rejection (AR): the group experiencing BU preceding AR had significantly (P < 0.001) lower eGFR compared with the group that experienced only AR (21 mL/min/1.73 m2 vs. 48 mL/min/1.73 m2 ), as a result of increased prevalence of combined rejections within the BU group. CONCLUSION Indwelling urological catheters and preceding ASB are associated with developing AGPN. An incident of AGPN itself does not impair renal allograft function 1 year after Tx. However, a relevant interaction occurs between BU and AR, in which the sequence of occurrence of these 2 events synergistically impairs the eGFR.

SUMMARYT3/4.A is a non-mitogenic murine IgA mAb to human CD3 that was selected for clinical studies to provide an alternative for the mitogenic, T cell-activating, therapeutic mAb OKT3. Previously, we reported that T3/4.A is better tolerated in humans than the IgG2a-CD3 mAb T3/4.2a. Here we report the results of a phase II clinical trial to assess the immunosuppressive potential of T3/4.A. Eighteen first kidney transplant recipients with a first rejection episode were included. Baseline immunosuppression consisted of cyclosporin and prednisolone. Rejection treatment consisted of 5 mg mAb per day during 10 days. Fourteen patients responded, of whom four experienced a second rejection within 2 weeks, one experienced chronic rejection after 2·5 years, whereas the others remained rejection-free after treatment (median duration of follow-up 42 months). Four patients did not respond and eventually lost their graft. These results are similar to treatment results with OKT3, as reported in the literature. Following the first dose of T3/4.A, side effects were limited, and reduced compared to OKT3-treated controls. On the second day, 15 patients developed transient vomiting and/or diarrhoea, which coincided with elevated serum levels of proinflammatory cytokines. Minimal or even no side effects occurred during the remaining days, which is in sharp contrast to that seen generally during OKT3 treatment. Both T cell numbers and TCR expression were reduced during the therapy. We conclude that T3/4.A is a good alternative for OKT3 to treat rejection episodes in renal transplant recipients.

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8(+) cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA(-)CD27(+)CCR7(-) CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4(+) T cells is necessary for recovery of infection.

Background The use of potent immunosuppressive drugs and increased travel by renal transplant recipients (RTR) has augmented the risk for infectious complications. Immunizations and changes in lifestyle are protective. The Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group has developed guidelines on vaccination following solid organ transplantation. The degree of adherence to these guidelines is unknown, as is which barriers must be overcome to improve adherence. Methods We performed a cross-sectional national survey among Dutch nephrologists to assess vaccination policy and adherence to the KDIGO guidelines. In addition, to investigate awareness and attitude of RTR regarding their risk of infection, we performed a cross-sectional survey of RTR in our outpatient clinic. Results A total of 132 (63%) nephrologists completed the survey. Reported immunization rates were 90.8% for influenza and 27.3% for hepatitis B. However, pneumococcal, tetanus toxoid, and meningococcal immunization rates were low. Twenty-seven percent of respondents were familiar with the guideline contents. The most frequent perceived barrier to guideline adherence was expectation of low effectiveness. A total of 403 RTR (62%) completed the survey. Sixty-eight percent perceived more risk for complicated infection. A significant correlation was found between education level and variables concerning awareness and attitude toward risk of infection. Conclusions Our results show that nephrologists' knowledge of and adherence to the recommendations regarding immunization after renal transplantation is suboptimal. Most Dutch RTR are aware of their increased risk and the possible seriousness of infectious complications. However, their behavior does not match their awareness. This disparity points to an important role for nephrologists in providing adequate counseling.

Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (-15%), and a trend was observed for everolimus (-7%) and tacrolimus (-16%). Patients carrying at least one CYP3A5*1 allele had 1.5-fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated.CPT: Pharmacometrics Systems Pharmacology (2014); 3, e100; doi:10.1038/psp.2013.78; published online 12 February 2014.

In an attempt to decolonise the patient from the ESBL producing E. coli, he underwent donor feces infusion in May 2013. Prior to this intervention, the presence of ESBL producing E. coli in the large intestine was again confirmed by a positive rectal culture. In addition his throat and perineum were also screened for the presence of ESBL producing Enterobacteriaceae, but both were negative. Culture of the urine was not possible because of the anuric condition of the patient. The donor feces infusion was performed according to the protocol as used in the FECAL trial [1]. In summary, donor feces were obtained from a young healthy Caucasian adult, who was periodically screened for various infectious and gastro-intestinal diseases. Feces from the donor were collected and processed within 6 h after production. First, the feces were diluted with sterile saline, and then poured through unfolded gauze in a funnel, in order to obtain a solution which was free of debris and solid particles. This solution was immediately infused in the patient through a nasoduodenal tube. Donor feces infusion was preceded by full colon lavage without prior use of antibiotics. Within the first 2 days after donor feces infusion the patient experienced mild diarrhoea and abdominal cramps, but no other adverse events occurred. Follow-up ESBL swab cultures of the rectum, perineum and throat were taken at week one, two, four, and twelve after the donor feces infusion. During these four follow-up time points the ESBL cultures of the

In recent years solid organ transplantation has been rapidly developed as a therapeutic intervention that is life-saving and greatly contributes to a better quality of life in organ recipients. The rapid development has been made possible because of a drastic expansion in the immunosuppressive repertoire. Unfortunately, the side effects of these drugs can be severe, which is one of the reasons that life expectancy of transplant patients still significantly falls short of that of the general population. In this review manuscript we will discuss current and future immunosuppressive strategies that are employed in solid organ transplantation. Expanding our understanding of the human immune system will hopefully provide us with newer, smarter drugs that promote immunotolerance without the side effects observed today.

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

Introduction Complications of the transplant ureter are the most important cause of surgical morbidity after renal transplantation. The presence of ureteral duplication in the renal graft might result in an increased complication rate. We analyzed our data of double-ureter renal transplantations using a case-control study design. Additionally, we performed a review of the literature. Methods From January 1995 to April 2012, 12 patients received a donor kidney with a double ureter (0.8%). We created a control group of 24 patients matched in age, sex, donor type, and ureteral stenting. Patient charts and surgical reports were reviewed retrospectively. Results In 7 patients both ureters were separately anastomosed to the bladder. In 4 patients a common ostium was created. In 1 patient 1 of the 2 ureters was ligated. No postoperative urologic complications occured. In the single-ureter group, the urologic complication rate was 17% (P = .71). Mean creatinine levels after transplantation were comparable between both groups. Discussion A double-ureter donor kidney is not associated with an increased complication rate after renal transplantation and yields equal outcomes as compared to single-ureter donor kidneys. We conclude that transplantation of a kidney with a duplicated ureter is safe.

Pre-existing occlusion of the inferior vena cava may complicate renal transplantation. Suppurative abdominal wall phlebitis following renal transplantation was diagnosed in a patient with pre-existing thrombosis of the inferior vena cava of unknown cause. The phlebitis developed in the subcutaneous collateral veins of the abdominal wall contra-laterally to the renal transplant. Cultures from abdominal wall micro-abscesses yielded Prevotella bivia as the causative agent. This complication has not been described before in the context of renal transplantation. The pathogenesis and management of this serious complication are discussed in this paper.

In this study, we assessed the safety of the new organ preservation solution polysol solution in the clinical setting of living kidney transplantation. We conducted a prospective pilot study in nine adult donor-recipient couples using polysol solution for washout and cold storage of kidney grafts. Adverse reactions possibly related to the use of polysol solution as well as renal function at 1, 6, and 12 months after transplantation were monitored. All living kidney transplantation performed in adults in our center within 2002 to 2008 using the University of Winconsin solution served as controls (n = 190). The use of polysol solution was associated with a higher acute rejection rate compared to University of Wisconsin solution at all time points. Also, antibody-mediated rejection occurred more frequently in the polysol group. Renal function at all time points was also comparable between the groups. This pilot study in living kidney transplantation is the first clinical study on the use of polysol solution. Although the study was not powered on the endpoint rejection, we observed a high number of acute rejection and antibody-mediated rejection episodes in recipients of polysol solution preserved grafts as compared to University of Wisconsin solution controls. As a consequence the study was terminated prematurely.

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 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.

CD8+ T-cell responses against latent viruses can cover considerable portions of the CD8+ T-cell compartment for many decades, yet their initiation and maintenance remains poorly characterized in humans. A key question is whether the clonal repertoire that is raised during the initial antiviral response can be maintained over these long periods. To investigate this we combined next-generation sequencing of the T-cell receptor repertoire with tetramer-sorting to identify, quantify and longitudinally follow virus-specific clones within the CD8+ T-cell compartment. Using this approach we studied primary infections of human cytomegalovirus (hCMV) and Epstein Barr virus (EBV) in renal transplant recipients. For both viruses we found that nearly all virus-specific CD8+ T-cell clones that appeared during the early phase of infection were maintained at high frequencies during the 5-year follow-up and hardly any new anti-viral clones appeared. Both in transplant recipients and in healthy carriers the clones specific for these latent viruses were highly dominant within the CD8+ T-cell receptor Vβ repertoire. These findings suggest that the initial antiviral response in humans is maintained in a stable fashion without signs of contraction or changes of the clonal repertoire., Author Summary Several viruses have found ways to evade the human immune system and cause latent infections. Examples include HIV and herpes-viruses. Most humans carry these herpes-viruses. The human immune system mounts continuous responses against these viruses to prevent them from causing disease. If this balance is disturbed, these viruses can cause extensive pathology. We do not know how the immune response against these viruses evolves over time. Understanding this response might help to understand why the immune system does not clear these viruses and might help in preventive and therapeutic strategies. Here we used a new technology that allowed us to track virus specific immune cells (CD8+ T cells) over time in a quantitative manner. When we used this technology to study the evolution of latent responses against herpes-viruses (from infection until 5 years later) we found that immune responses were very rigid and did not evolve over time. Collectively our data shows that – for these herpes-viruses – the initial immune response is maintained despite the fact that this does not result in clearance of the virus. Therefore, if a virus survives the initial response, it will not be cleared in the future. This is an important consideration in understanding latent infection and for vaccination-design.

In the present study the consequences of administration of low-dose (0.5 mg) OKT3 for respiratory side-effects and pulmonary sequestration of labelled granulocytes are compared with the known effects of 5 mg OKT3. Ten renal transplant patients were studied, of whom five were treated with 0.5 mg OKT3 and five with 5 mg OKT3. None of the patients in the 0.5 mg group and two of the patients in the 5 mg group experienced dyspnoea. Sequestration of labelled granulocytes in the lungs was significantly lower in the patients receiving 0.5 mg OKT3 compared with the patients receiving 5 mg OKT3. The simulataneously occurring peripheral blood granulocytopenia was significantly more severe in the 5 mg group than in the 0.5 mg group. We suppose that this sequestration of circulating granulocytes in the lungs is at least partly mediated by complement activation products. In vitro it is demonstrated that fixation of complement activation products on peripheral blood lymphocytes depends on the concentration of OKT3 present in the culture medium. We conclude that respiratory side-effects shortly following infusion of OKT3 are related to complement-induced pulmonary leucostasis, the degree of which is dependent on the administered dose of OKT3.

A 28-year-old man with a thyroid stimulating hormone/prolactin (TSH/PRL)-secreting pituitary macroadenoma is discussed in relation to dopamine D2 and somatostatin receptor single-photon emission tomography (SPET). The patient presented with decreased vision in the left eye as a result of a temporal visual field defect and with mild hyperthyroidism. Medical therapy was tried. A test dose of both octreotide and bromocriptine resulted in an acute reduction in serum levels of TSH, alpha-subunits and PRL, whereas there was no response to TRIAC. Somatostatin and dopamine D2 receptors were present on the tumour as visualised by SPET with the ligands indium-111 diethylene triamine penta-acetic acid (DTPA)-octreotide (111In-SMS) and iodine-123 iodobenzamide (123I-IBZM), respectively. Therefore, treatment with octreotide 150 micrograms t.i.d. subcutaneously and bromocriptine 10 mg b.i.d. orally was given for > 12 and > 6 weeks, respectively. Following this treatment the visual defects disappeared, although tumour size, as measured by CT scanning, and serum TSH levels did not decrease. SPET with 111In-SMS and 123I-IBZM after therapy revealed no change or a possible increase in somatostatin receptor binding potential and a possible decrease in dopamine D2 receptor binding potential. The lack of long-term effects of the medical treatment is discussed. It is concluded that a high somatostatin and dopamine D2 receptor binding potential in vivo in a TSH/PRL-producing adenoma does not necessarily predict a successful outcome of medical treatment

Background. Delayed graft function (DGF) has a negative effect on the results of living-donor kidney transplantation. Objective. To investigate potential risk factors for DGF. Methods. This prospective study included 200 consecutive living donors and their recipients between January 2002 and July 2007. Delayed graft function was defined as need for dialysis within the first postoperative week. Results. Delayed graft function was diagnosed in 12 patients (6%). Intraoperative complications occurred in 10 donors (5%), and postoperative complications in 24 donors (13.5%). One-year kidney graft survival with vs without DGF was 52% and 98%, respectively (P

De nieren liggen min of meer goed beschermd in de retroperitoneale ruimte en zij worden samen met de bijnieren omgeven door de fascia van Gerota.

A fatal case is reported concerning a severely immunocompromised 50-year-old female renal transplant recipient who developed fever and confusion. Cerebral imaging with contrast-enhanced computed tomography (CT) scans showed no abnormalities while subsequently performed magnetic resonance imaging (MRI ) showed clear abnormalities in the basal ganglia. By that time serology and polymerase chain reaction had confirmed the diagnosis of cerebral toxoplasmosis. Because of the suboptimal sensitivity of these tests negative results should be handled with care. Once cerebral toxoplasmosis is suspected in at-risk patients, treatment should be started empirically pending the confirmation of the diagnosis. A normal cerebral CT scan does not preclude cerebral toxoplasmosis.In these situations MRI can give important additional information.

Recently two major outbreaks of mumps have occurred: in the UK more than 56,000 cases were notified between 2004 and 2005, and in the United States, 6,584 cases were reported in 2006. Most patients were young healthy adults, in whom mumps normally has a benign course. Little is known about mumps in the immunocompromised patient. Here, we report a case of a 56-year renal transplant recipient who developed acute irreversible transplant failure due to interstitial nephritis caused by mumps. RNA of the mumps virus was detected in the urine as well as in a renal biopsy. In view of the ongoing presence of the mumps virus in the population, one should be aware of the possible occurrence of this infection in immunocompromised patients.

The number of renal transplant recipients is increasing steadily. Physicians from all specialties are ever more likely to encounter this vulnerable group of patients. They constitute a susceptible group because of increased mortality and morbidity. Half of the renal transplants are lost due to chronic transplant failure. The primary cause of chronic transplant failure is chronic allograft nephropathy. Other causes of transplant failure are calcineurin inhibitor toxicity, recurrence of the original renal disease such as glomerulonephritis and diabetes mellitus, stenosis of the renal artery in the transplant, and urological complications. The other half of the renal transplants are lost due to the death of the recipient. The primary cause of death is cardiovascular disease due to former chronic renal, hypertension and dyslipidemia following the use of immunosuppressants. In addition malignancies, infections and bone abnormalities do occur more frequently as compared to the normal populations. Alertness is warranted following kidney transplantation by both the patients themselves as well as all the treating specialists. Careful periodical monitoring for life is required because of the risk of the abovementioned complications.

To evaluate the results of the first 100 hand-assisted donor nephrectomies in our hospital.Prospective, descriptive.In the period January 2000-July 2004, 100 consecutive donors underwent laparoscopic nephrectomy as part of a living-related kidney transplantation at the Academic Medical Center in Amsterdam, the Netherlands. The operation was performed laparoscopically using a hand port (hand-assisted nephrectomy). The incision made for the hand port was also used for the removal of the kidney.Mean operating time was 168 min (range: 88-285). Median warm ischaemia time was 3 min (1.0-4.5) and median blood loss was 50 ml (20-1500). None of the operations required conversion to an open procedure and there were no deaths among donors or recipients. Postoperatively, 12 complications occurred in 10 donors. Median hospital stay for the donors was 5 days. In 3 recipients, the transplanted kidney had to be removed within 14 days. 1n 3 other recipients, surgical re-intervention was necessary due to urological complications. One-year graft survival was 94%.Hand-assisted laparoscopic donor nephrectomy was a safe and minimally invasive procedure for renal transplantation in this patient series.

We describe a case-report of a chylous ascites after laparoscopic donor nephrectomy, summarize the current literature, and hypothesize on the etiology of this complication.