Search

Background: Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact., Methods: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome., Results: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge., Conclusions: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.

Background: Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities. Compliance describes the degree to which patients follow medical advice and take their medications. Adherence has been defined as the extent to which a patients' behavior coincides with clinical prescriptions., Materials and Methods: Patients were randomized 7 to 14 days after transplantation into groups with (n = 40) and without (n = 40) an electronic medication dispenser (EMD). The EMD, which was used for the 1-year study period, recorded the date and time the patient took their medications and was monitored via a web-based application. Patients were monitored for 1 year regarding outpatient follow-up visits, emergency hospitalizations, renal biopsies, rejection episodes, renal function, and blood concentration of medications., Results: Compliance in the intervention group was 97.8% (the control group was not assessed). Number of missed doses varied significantly by weekday (P = 0.033); patients were most likely to miss doses on Saturdays and Thursdays. Patients missed a total of 11 follow-up visits. During the study, 92 biopsies were performed on 55 patients (intervention group: 32 [17]; control group, 60 [38]). Biopsy-verified rejection was three times more common among controls (13 patients vs. 4; P = 0.054, not significant). Average P-creatinine level was slightly lower in the intervention group than the control group (131 vs. 150 μmol/L, not significant), whereas mean tacrolimus was similar (7.32 vs. 7.22 ng/mL, n.s.)., Conclusions: The EMD is associated with high compliance, and there are also indications of a lower rejection rate.

Background: Patients with autosomal dominant polycystic kidney disease (ADPKD) often need to undergo native nephrectomy and are candidates for kidney transplantation. The necessity and timing of nephrectomy are controversial. Some authors recommend simultaneous bilateral native nephrectomy (SBN) as the preferred option in living-donor kidney transplantation (LDKT). These recommendations are based on small study populations. We therefore set out to study outcomes of LDKT with SBN, compared with LDKT alone in a larger single-center cohort., Methods: A consecutive series of 159 patients with ADPKD undergoing LDKT were included in the study. Of the 159 patients, 2 were excluded because of missing data, 79 underwent LDKT alone (group A), and 78 underwent LDKT with SBN (group B). Demographic data and intraoperative and postoperative data were collected from patient charts and the national kidney registry., Results: There were no differences regarding background data. Group B experienced significantly longer operating times (183.7 vs. 319.3 min, P<0.001), a greater need for blood transfusions (0.1 vs. 1.6 units, P<0.001) and plasma products (35.1 vs. 438.3 mL, P<0.001), and longer hospital stays (11.8 vs. 15.4 days, P<0.001). It also experienced more intraoperative events and postoperative complications but fewer reoperations/reinterventions. There were no differences in patient and graft survival rates., Conclusions: SBN in patients undergoing LDKT for ADPKD does not have a significant negative impact on patient and graft survival rates. It obviates a separate surgical procedure but requires longer hospital stay. It may be associated with more postoperative complications and risk of graft loss. These considerations should be communicated to the recipient and the donor.

Background: Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation., Methods: All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day -30 and postoperative day 30. C1q was measured on day -30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma., Results: Patient and graft survival were 100% for a median follow-up of 40 months (range, 12-60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day -30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected., Conclusions: The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.

Background: Hand-assisted and retroperitoneoscopic techniques reduce the risk of bleeding and intraabdominal complications in living donor nephrectomy (LDN). This study reports on our four-center experience, development, and learning curves from the first 413 LDNs using a hand-assisted retroperitoneoscopic (HARS) technique., Methods: The first 413 consecutive donors operated on using HARS were included in the study. Donor demographics, perioperative and postoperative data, complications, and recipient outcomes have been compiled. The data were analyzed as a whole and separately for each center, looking at center differences and learning curves over time., Results: Significant differences were found in donor demographics between centers for the variables: age, body mass index, number of arteries, and side of operation. Mean operating time was 170.2 min, with significant differences between centers. Operating time was also significantly influenced by learning curves, sex/body mass index, and side of operation. Warm ischemia time differed significantly between centers and was influenced by center-wise learning and number of arteries. Overall conversion rate was 2.4% and differed significantly between centers. There was no mortality and no intraabdominal complications. Apart from the conversions and one pulmonary embolism, there were no major intraoperative or postoperative complications. Overall 3-month graft survival was 99%, with 96% immediate onset of function and 1% ureteral complications., Conclusions: The HARS technique reduces the risk of intraabdominal complications. It can be implemented with excellent donor and recipient outcomes despite different population demographics and center/surgeon-related tradition and experience. On the basis of our experience, we recommend the technique to increase the safety margin of LDN.

Unlabelled: We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event., Results: We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depletion of CD19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66+/-22 mL/min in the study group and 67+/-23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections., Conclusion: We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.

Aim: The aim of this study was to evaluate risk factors for venous thromboembolism (VTE) and deep vein thrombosis after living donor nephrectomy in a center using extensive preoperative screening and perioperative venous duplex scan., Material and Methods: Thrombophilia screening and pre- and postoperative ultrasonographies were performed in 130 consecutive living kidney donors (laparoscopic 105, open 25). Donors were followed prospectively for at least 3 months. All donors received prophylaxis with the low molecular weight heparin enoxaparin and compression stockings. Donors with increased risk received a double dose of enoxaparin and the prophylaxis was continued for 6 weeks. Donors with venous thrombosis at discharge duplex also received prolonged prophylaxis., Results: The frequency of thrombophilia was similar to what can be expected in the Swedish population (four with factor V Leiden and one each with protein S deficiency, prothrombin gene mutation, and anticardiolipin antibodies). Preoperative duplex was normal. Three donors had small postoperative deep vein thrombosis. Twelve donors (9.2%) received an intensified and prolonged prophylaxis. No further thromboembolic complications developed in 3 postoperative months., Conclusion: With the present protocol for preoperative evaluation, perioperative duplex screening, and prophylaxis, the risk of postoperative VTE is low after living donor nephrectomy. Given that 9.2% had risk factors or developed deep vein thrombosis, the extraordinary situation of an operation being performed on a healthy person who has no therapeutic benefit and the low incidence of VTE in the present study, we recommend the presented approach to be implemented more broadly and that further studies are performed in larger cohorts.

Background: A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany., Methods: The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period., Results: Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala., Conclusions: The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.

Background: The two major life-threatening complications associated with laparoscopic live donor nephrectomy are sudden severe bleeding and intestinal injury. A combined technique-hand-assisted and retroperitoneoscopic (HARS)-reduces the risk of these life-threatening complications. In this study, we report on our experience from the first 75 consecutive HARS operations., Methods: The data has been collected prospectively according to intention to treat and includes all consecutive donors operated with the HARS technique. Warm ischemia time, operating time, and blood loss were recorded. Complications, convalescence, and allograft outcome were followed postoperatively with a mean follow-up of 701 (range 60-1438) days., Results: The mean operating time was 138 (range 85-260) minutes and the mean warm ischemia time 175 (85-510) seconds. The operative time was significantly longer in male donors. The mean bleeding was 176 (50-700) ml. There were no conversions to open surgery. Major complications comprised one pulmonary embolus and one donor required 2 units of blood transfusion. One donor was reoperated due to suspicion of trocar hernia. Nine patients experienced minor complications (fever, n=4; urinary tract infection, n=2; chylous ascites, n=1; orchialgia, n=1; subcostal pain, n=1). All except two kidneys had immediate onset of function. Neither of these could, however, be attributed to the donor operation. One recipient experienced urinary leakage and one a stenosis. Recipient and graft survival were 99% and 96%, respectively., Conclusions: We conclude that HARS facilitates the procedure by enabling short operating times and at the same time significantly reducing the risks associated with endoscopic live donor nephrectomy.

Background: Living donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on a healthy individual. A new hand-assisted retroperitoneoscopic nephrectomy (HARS) technique was compared to transperitoneal laparoscopic nephrectomy (LAP) and open nephrectomy (OPEN). The aim was to examine the perioperative and postoperative morbidity, and the effects of the different surgical techniques with regard to renal function., Methods: Donors (n=36) were divided into three groups (HARS, LAP and OPEN) according to surgical technique. During the operations, renal function, hormone output, warm ischemia time (WIT) and operating time were recorded. Renal function, complications, convalescence and allograft outcome were followed postoperatively for one year., Results: OPEN and HARS groups showed similar operation times: 150 (95-218) minutes and 145 (124-225) minutes, respectively. LAP procedures took longer: 218 (163-280) minutes. OPEN had the shortest WIT at 91 (55-315) seconds; LAP had the longest WIT at 207 (100-319) seconds, with HARS at 180 (85-240) seconds. In all groups, glomerular filtration rate and urine production were decreased during surgery. Endoscopic techniques had a higher catecholamine release, and OPEN donors showed higher serum aldosterone. Endoscopic techniques showed shorter convalescence and less postoperative pain compared to OPEN. HARS had a smaller rise in creatinine than LAP, and HARS recipients a better creatinine clearance than the other groups in the early posttransplantation period., Conclusions: Evaluation of HARS shows that the operation is quick, the donors experience little pain, and recovery time is short. The renal function for donors and recipients is somewhat favorable to open surgery and transperitoneal laparoscopic approaches.

Background: Most living-donor nephrectomies are performed either by transperitoneal laparoscopy, with or without hand assistance, or by retroperitoneal open surgery, with or without video assistance. We therefore started to combine the benefits of these techniques: hand assistance to increase safety and control of the laparoscopic technique, and the retroperitoneal approach to minimize the risk of complications associated with the transabdominal approach. Herein, we report on our first 10 donors nephrectomized with hand-assisted retroperitoneoscopy., Results: Only left nephrectomies were performed. One donor had two renal arteries and two donors had retroaortic renal veins. There were no intra- or postoperative complications. Mean operating time was 155 min (110-230 min)., Conclusions: Hand-assisted retroperitoneoscopy in living-donor nephrectomy is a promising new method that could reduce the risks of traditional transperitoneal laparoscopy and should be further evaluated.

Background: Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects 50-90% of individuals in different populations. After primary infection, the virus persists latently in myeloid cells under the control of specific T-cells. Reactivation of CMV infection may cause lethal organ dysfunction and is frequently seen in immunosuppressed individuals. CD8+ cytotoxic T-cells (CTL) have a primary role in suppressing CMV reactivation, and the dominating CTL response is directed against pp65., Methods: MHC tetramers, that is, complexes between HLA class I (or class II) molecules and antigenic peptides conjugated to fluorochromes allow the direct visualization of antigen-specific receptor-carrying T-cells using flow cytometry. We constructed a novel MHC tetramer for identification of CMVpp65-specific CD8+ T-cells using HLA-A2 molecules folded with the immunodominant NLVPMVATV peptide., Results: The A2/pp65 tetramer specifically stained CMV-directed T-cell lines, and sorted cells showed CMV-specific cytotoxicity. High proportions (0.1-9%) of the CD8+ T-cells were A2/pp65 tetramer+ in healthy HLA-A2+ CMV carriers and in immunosuppressed kidney transplant patients with latent infection. Patients with reactivated CMV infection exhibited up to 15% A2/pp65 tetramer+ cells, which seemed to correlate with CMV load over time. A2/pp65 tetramer+ cells expressed T-cell activation markers., Conclusions: The construction of a novel A2/pp65 MHC tetramer enabled the design of a rapid and precise flow cytometric method allowing quantitative and qualitative analysis of CMV-specific T-cells. The number of A2/pp65 tetramer binding CTLs in blood may prove to be clinically relevant in assessing the immune response to CMV.