Stabilization of renal function after the first year of follow-up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus-associated nephropathy.

BACKGROUND: BK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV-associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow-up periods. METHODS: We reviewed the outcome of our screening and immunosuppression reduction protocol in 305 patients who received a kidney transplant between March 2008 and January 2013. Quantitative BKPyV DNA surveillance in plasma was performed at 1, 2, 3, 6, 9, and 12 months after transplantation. Patients with significant viremia and/or biopsy-proven BKPVAN were treated with immunosuppression reduction and leflunomide. RESULTS: During the first post-transplant year, 24 patients (7.9%) developed significant viremia at a median time of 95 days, and 18 patients had BKPVAN; 23 of the 24 (7.5%) were treated according to our protocol (group BKV+); 225 patients (73.8%) did not develop any BK viremia (group BKV-). Allograft function was similar in both groups at 1 month post transplantation (P=.87), but significantly worse at 1 year in the BKV+ group (P=.002). Thereafter, kidney function stabilized in the BKV+ group and no differences in patient and graft survival were seen between the groups after a median follow-up of 4 years. CONCLUSIONS: We confirm the early occurrence of BKPyV replication after transplantation and the short-term decline in renal function. However, early detection of BKPyV replication, prompt diagnosis, and reduction in immunosuppression may offer long-term benefits for graft function.

BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches.

BK polyomavirus is ubiquitous, with a seropositivity rate of over 75% in the adult population. Primary infection is thought to occur in the respiratory tract, but asymptomatic BK virus latency is established in the urothelium. In immunocompromised host, the virus can reactivate but rarely compromises kidney function except in renal grafts, where it causes a tubulointerstitial inflammatory response similar to acute rejection. Restoring host immunity against the virus is the cornerstone of treatment. This review covers the virus-intrinsic features, the posttransplant microenvironment as well as the host immune factors that underlie the pathophysiology of polyomavirus-associated nephropathy. Current and promising therapeutic approaches to treat or prevent this complication are discussed in relation to the complex immunopathology of this condition.

Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score.

PURPOSE: Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years. PATIENTS AND METHODS: A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses. RESULTS: Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 µmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high-risk recipients. CONCLUSION: This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Prevention of CMV disease in pediatric kidney transplant recipients: evaluation of pp67 NASBA-based pre-emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high-risk patients.

A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre-emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV-IG in high risk (R-/D+) children. Thirty-one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R-/D+ patients were given prophylactic CMV-IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D- patients and 10 (72%) of the R-/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R-/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV-IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA-based pre-emptive ganciclovir therapy, combined with prophylactic CMV-IG in high-risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV-IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high-risk populations.

Complete robotic-assistance during laparoscopic living donor nephrectomies: an evaluation of 38 procedures at a single site.

OBJECTIVE: To evaluate our initial experience with entirely robot-assisted laparoscopic live donor (RALD) nephrectomies. METHODS: From January 2002 to April 2006, we carried out 38 RALD nephrectomies at our institution, using four ports (three for the robotic arms and one for the assistant). The collateral veins were ligated, and the renal arteries and veins clipped, after completion of ureteral and renal dissection. The kidney was removed via a suprapubic Pfannenstiel incision. A complementary running suture was carried out on the arterial stump to secure the hemostasis. RESULTS: Mean donor age was 43 years. All nephrectomies were carried out entirely laparoscopically, without complications and with minimal blood loss. Mean surgery time was 181 min. Average warm ischemia and cold ischemia times were 5.84 min and 180 min, respectively. Average donor hospital stay was 5.5 days. None of the transplant recipients had delayed graft function. CONCLUSIONS: Robot-assisted laparoscopic live donor nephrectomy can be safely carried out. Robotics enhances the laparoscopist's skills, enables the surgeon to dissect meticulously and to prevent problematic bleeding more easily. Donor morbidity and hospitalization are reduced by the laparoscopic approach and the use of robotics allows the surgeon to work under better ergonomic conditions.

Robot-assisted laparoscopic and open live-donor nephrectomy: a comparison of donor morbidity and early renal allograft outcomes.

BACKGROUND: Robot-assisted laparoscopic donor (RALD) nephrectomy, a new procedure for the removal of a kidney from a living donor, was performed on 13 subjects at our centre. METHODS: The immediate post-operative courses for these donors, and their respective recipients, were compared with those of 13 previous open live-donor nephrectomies (OPEN), performed in our facility. RESULTS: We found no significant differences between these two donor groups with respect to age, gender, body mass index or renal vasculature. The average operative times and the warm ischaemia times were greater in the RALD group, 185.5'' vs 113.4'' (P = 0.0001) and 7'15'' vs 1'41'' (P = 0.0001), respectively. There was no conversion to the open procedure in the RALD group. The estimated blood loss was slight in both groups. Following nephrectomy, deep venous thrombosis occurred in one RALD patient and acute pyelonephritis in one OPEN patient. The average duration of hospitalization was shorter after the RALD procedure (5.84+/-1.8 days vs 9.69+/-2.2 days, P = 0.0001). The estimated creatinine clearance rate (eClcreat) was equivalent for all donors, at 5 days and 1 month after nephrectomy. All kidneys started functioning immediately after the transplantation. The mean recipient eClcreat (ml/min) was 58.16+/-26.7 for OPEN group kidneys and 62.23+/-17.59 for RALD group kidneys (P = 0.65), 5 days after transplantation. CONCLUSIONS: RALD nephrectomies were associated with very low morbidity among donors, in which both the operative and warm ischaemia times were of longer duration, but had no observable adverse effects upon short-term graft function.

Infectious risk in pediatric organ transplant recipients: is it increased with the new immunosuppressive agents?

The risk of infection in pediatric organ transplant recipients is determined by several factors, including age, the types of organ transplanted and the immunosuppressive treatment which has dramatically changed over the past 10 yr. Little information has been reported regarding the infectious complications related to the current immunosuppressive protocols used in these children. This paper reviews (i) the immunosuppressive agents, focusing on their mechanisms of action and on the new regimens, (ii) the infections related to excessive immunosuppression and also anti-infectious properties or infectious adverse reactions associated with specific immunosuppressive agents. With the new immunosuppressive protocols, the advances in immunologic monitoring, microbiological diagnosis, anti-infectious prophylactic and preemptive treatments, strategies to minimize the risk of infection related to the immunosuppressive therapy are proposed.

Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation.

BACKGROUND: Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium. METHODS: All pancreata offers to the University of Geneva Cell Isolation and Transplantation Center from within the network in 2002 and 2003 were reviewed. Islet preparations were attributed to the most suitable recipient on a centrally managed waiting list. All shipments were performed by ambulance in less than 5 hr. RESULTS: Over the period of study, 260 pancreata were offered, from a total of 1,304 cadaveric donors in the four allocation regions (20%). Fifty-two patients were on the waiting list at any time during this 2-year period. The percentage of organs offered varied in the range of 0.5% to 42%, depending on region of origin, with a correlation with number of patients on the waiting list in each region. Of these, 104 (40%) were accepted for processing. Ninety-two pancreata were actually processed, resulting in 42 islet preparations being transplanted. The number of international equivalents of transplanted preparations was 378,500+/-16,000 versus 165,400+/-15,400 (P<0.0001) for nontransplanted preparations. Total cold ischemia time was 6+/-0.3 hr for transplanted preparations versus 6.7+/-0.4 hr for nontransplanted preparations (not significant). CONCLUSIONS.: A high rate of pancreas offers, successful isolation, and islet transplantation can be achieved in multicenter networks such as GRAGIL. Such an approach can expand both the donor pool and the recipient population.

Is routine chest radiography necessary for the initial evaluation of fever in neutropenic children with cancer?

BACKGROUND: The yield of routine chest radiography (CXR) as part of the initial management of febrile neutropenic pediatric oncology patients is questionable. PROCEDURE: We retrospectively analyzed the clinical records of neutropenic (absolute neutrophil count < or = 0.5 x 10(9)/L) children with cancer, admitted with oral temperature > or = 38 degrees C to our institution, between January 2001 and October 2002. Following admission, patients received tobramycin plus (piperacillin or ticarcillin-clavulanic acid). Admission routine CXRs were reviewed. Clinical and radiological features were compared with the discharge diagnosis. Age, underlying disease, and the presence of pulmonary symptoms or signs were studied as possible predictors of CXR findings related to pneumonia. RESULTS: In total, 88 patients experienced 170 episodes of fever. A routine admission CXR was obtained for 157 of the episodes. Radiologists found 20 (12.7%) abnormal CXR (6 with a segmental or lobar consolidation considered as a pneumonia). In addition, two patients with abnormal admission CXR developed lobar consolidation on a repeat film, later in their hospital course. There were no differences in age and type of underlying disease between children with or without pneumonia. Respiratory symptoms were initially present in 58 cases. Seven (12%) had pneumonia. Among the 99 asymptomatic cases only one (1%) patient had a pneumonia (P = 0.0041). This child had a positive blood culture for P. aeruginosa at the time of admission. None of the children had initial therapy modified on the basis of radiologic findings. CONCLUSION: In this study, pneumonia is an unusual cause of fever (5%), especially in the absence of respiratory signs or symptoms (1%). Admission CXR should be reserved for the neutropenic pediatric oncology patient presenting with fever and abnormal respiratory findings.

Influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients within the Swiss-French GRAGIL network.

BACKGROUND: The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network. PATIENTS AND METHODS: From December 2001 to April 2003, 16 human pancreatic islet transplants were performed in 9 type 1 diabetic patients with an established kidney graft (functioning for at least 6 months) in four centers of the GRAGIL network. Islet isolation was performed in a core laboratory in Geneva, and the islet preparations were shipped by ambulance to each center for transplantation. One month after transplantation, the efficiency of the graft was assessed according to islet transportation time (ITT): ITT less than 2 hours (group 1, n=5), and ITT greater than 4.5 hours (group 2, n=4, mediant 5 hours). RESULTS: Primary graft dysfunction was observed in one patient in group 1 after one month. Two patients became insulin independent in groups 1 and 2. All other patients in both groups had a plasma C-peptide level greater than 0.5 ng/ml. The HbA1c level and the exogenous insulin needs decreased in both groups. CONCLUSIONS: ITT does not seem to influence the efficiency of pancreatic islet allotransplantation in type 1 diabetic patients. These results emphasize the scope for multicenter networks such as the GRAGIL group.

Anti-HBs cellular immune response in kidney recipients before and 4 months after transplantation.

Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.