Mycosis fungoides in a lung transplant recipient with advanced ciclosporin nephropathy: management with mechlorethamine and subsequent renal transplantation.

Posttransplant cutaneous T cell lymphomas are rare and have been reported to have a poor prognosis. We report the case of a follicular mycosis fungoides in a lung transplant recipient who was successfully treated with topical mechlorethamine, prior to subsequent renal transplantation.

Facteurs influençant le retour au travail après transplantation chez 61 patients rénaux ou hépatiques

Le taux de retour au travail après greffe est généralement bas. Or, on sait que le retour au travail après greffe améliore la qualité de vie des transplantés. Le but de notre étude était donc de comprendre les raisons possibles à ce faible taux en montrant les facteurs professionnels, individuels ou médicaux pouvant l'influencer. Parmi les 61 greffés rénaux ou hépatiques suivis au centre de transplantation d'organe (CTO) du CHUV, 39% ont repris le travail après greffe. Trois facteurs étaient significatifs de retour au travail après greffe, à savoir «travail avant greffe», «diplôme» et «âge < 45 ans». Ainsi, il est utile pour la pratique médicale de connaître les facteurs potentiels influençant le retour au travail car cela permet d'évaluer, au stade prégreffe, les chances de retour au travail et si besoin de proposer des mesures spécifiques le favorisant.

Treatment of Recurrent Hepatitis C after Liver Transplantation with PEG-Interferon and Ribavirin.

Background and aim: Recurrent hepati tis C is a major cause of morbidity and mortality after li ver transpl ant ati on (LT), and optimal treatm ent algorithms have yet to be defined. Here, we present our experience of 22 patients with recurrent hepatitis C treated in our institution .Patients and methods: Twenty-two patients with hi stology-proven recurrent hepati tis Cafter LT were treated since 2003. Treatment was ini ti ated with pegylated interferon-a2a 135 IIg per week and ribavirin 400 mg per day in the majority of patients, and subsequent doses were adapted individllally based on on-treatment virologieal responses and c1inical and/or biochemical si de effeets.Results: On an intention-to-treat basis, ustained virological re ponse(SVR) was achieved in 12/21 (54.5%) patie nts (5/12 [41 .6%], 2/3 [67%], 4/5 [80%] and 1/2 [50%] of patients infected with genotypes 1,2,3 and 4, respectively). Two patients experieneed relap e and 6 did not respond to treatm ent (NR). Treatment duration ranged from 24 to 90 weeks. It was stopped prematurely due to adverse events in 6/22 (27.2%) patients (with SVR achieved in 2 patients, NR in 2 patients, and death of 2 patients: one patient awaiting retransplantation and a second patient with HCV-HJV co-infection and fibrosing cholestat ic hepatiti s, nine months after transplantation). Of note, SVR was achi eved in a patient \Vi th combined liver and kidney transplantation. Importantly, SVR \Vas ach ieved in some patients despite the lack ofan early virological response or HCV RNA negativity at week 24. Darbepoetin a and fil ~,'rasti m were used in 36% and 18%, respectively.Conclusion: Individually adapted treatment of recurrent hepatitis C canachieve SVR in a substantial proponion ofLT patients. Conventional stopping rules do not apply in this setting so that prolonged therapy may be useful in selected patients.

Urological complications in renal transplantation from cadaveric donor grafts: a retrospective analysis of 20 years.

INTRODUCTION: This study is a retrospective analysis of ureteral complications and their management from a monocenter series of 277 consecutive renal transplantations. MATERIALS AND METHODS: From September 1979 to June 1999, 277 renal transplantations (cadaveric origin) were performed in 241 patients. The ureter from the kidney graft was inserted into the bladder according to the technique of extravesical implantation described by Lich-Gregoir and Campos-Freire. The study analyzed the time of occurrence and the type of complications observed. The different procedures to restore the transplanted urinary tract are presented. RESULTS: Complications occurred in 43/277 renal transplantations (15.5%). Anastomotic urine leakage or ureteral stricture were the most frequent. The time to appearance of these complications was either short (<1 month) or late (>1 month) in a similar number of cases. Most cases were managed surgically: 33/43 cases (76.7%). The most frequent surgical repair was ureterovesical reimplantation (n=13), followed by: ureteroureteral end-to-end anastomosis (native ureter-ureter transplant, n=5); pyeloureteral anastomosis (native ureter-renal pelvis transplant, n=5); simple revision of ureterovesical implantation (n=4); resection and end-to-end anastomosis of the transplant ureter (n=2); calico-vesicostomy (graft-bladder, n=1); implantation according to Boari (n=1); pyelovesicostomy with bipartition of bladder (n=1), and pyeloileocystoplasty with detubularized ileal graft (n=1). No deaths related to any of the urological complications were reported. However, 2 consecutive vesico-renal refluxes led to the loss of the kidney graft in the long-term. CONCLUSION: The rate of complications observed in this retrospective analysis is similar to the experience of other studies, ranging from 2 to 20%. If the classical extravesical ureteral bladder implantation is to remain an attractive technique due to its simplicity, the surgical team at the training center should be aware of all the means to prevent any ureteral complications, such as the choice of another implantation technique and/or insertion of a transient ureteral stent.

Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant.

Since new technologies based on solid phase assays (SPA) have been routinely incorporated in the transplant immunology laboratory, the presence of pretransplantation donor-specific antibodies (DSA) against human leukocyte antigen (HLA) molecules has generally been considered as a risk factor for acute rejection (AR) and, in particular, for acute humoral rejection (AHR). We retrospectively studied 113 kidney transplant recipients who had negative prospective T-cell and B-cell complement-dependent cytotoxicity (CDC) crossmatches at the time of transplant. Pretransplantation sera were screened for the presence of circulating anti-HLA antibody and DSA by using highly sensitive and HLA-specific Luminex assay, and the results were correlated with AR and AHR posttransplantation. We found that approximately half of our patient population (55/113, 48.7%) had circulating anti-HLA antibody pretransplantation. Of 113 patients, 11 (9.7%) had HLA-DSA. Of 11 rejection episodes post-transplant, only two patients had pretransplantation DSA, of whom one had a severe AHR (C4d positive). One-year allograft survival was similar between the pretransplantation DSA-positive and -negative groups. Number, class, and intensity of pretransplantation DSA, as well as presensitizing events, could not predict AR. We conclude that, based on the presence of pretransplantation DSA, post-transplantation acute rejections episodes could not have been predicted. The only AHR episode occurred in a recipient with pretransplantation DSA. More work should be performed to better delineate the precise clinical significance of detecting low titers of DSA before transplantation.

No detectable indirect effects of late-onset Cytomegalovirus disease after valganciclovir (VGC) prophylaxis in kidney transplant recipients

Background: Cytomegalovirus (CMV) disease remains an important cause of morbidity after kidney transplantation and has been associated with acute rejection, graft loss and other indirect effects. A 3-month course of VGC prophylaxis reduces the incidence of CMV disease. However, little is known about the indirect effects of lateonset CMV disease after VGC prophylaxis. Objective: To evaluate the impact and indirect consequences of late-onset CMV disease after VGC prophylaxis in kidney transplant recipients. Methods: Retrospective analysis of 61 consecutive adult kidney transplant recipient with positive CMV serology (donor or recipient) who received VGC prophylaxis for 3 months and completed a follow-up of at least 2 years post-transplantation. Patients who developed CMV disease within 1 year after transplantation were compared to CMV disease-free patients for renal function (plasma creatinine values) at 1, 6, 12 and 24 months and for the incidence of graft loss, acute rejection, diabetes, cancer and opportunistic infections. Results: 8/61 (13%) patients developed CMV disease at a median of 131 days after transplantation (range: 98-220). The CMV incidence in D+/R- high risk patients was 6/18 (33%), while it was 2/43 (5%) in intermediate-risk patients (p < 0.01). All 8 patients were treated by oral valganciclovir (median 39 days; range: 19-119) with a complete resolution of CMV disease. As shown in the figure, there was no difference in creatinine values between the two groups at any time during follow-up. There was no graft loss, and the incidence of acute rejection, cancer and opportunistic infections did not differ between the two groups. The incidence of post-transplant diabetes was higher (38% vs 15%) in patients with CMV disease, but this difference was not significant (p = 0.4). Conclusions: An incidence of 13% of late-onset CMV disease was observed despite 3 months VGC prophylaxis. However, no indirect consequences were found. Moreover, therapy of CMV disease by oral VGC was effective and safe. Larger trials are needed to study whether late-onset CMV disease is associated with indirect consequences, as described with early-onset CMV.

Prevalence and significance of anti-HILA antibodies after liver transplantation : P236

Background: The pathogenic role of anti-HLA antibodies (AHA) after kidney transplantation is well established. However, its significance after liver transplantation remains unclear. The aim of our study was to determine the prevalence and significance of AHA after liver transplantation. Methods: Between January 2007 and November 2007, all liver transplant recipients who were greater than 6 months posttransplantation and followed regularly at our transplant outpatient clinic (n = 95) were screened for AHA. All clinical and electronic records were reviewed. Serum samples were tested using multiplex technology (Luminex). A liver biopsy had been performed in 55 out of the 95 patients based on clinical grounds but no routine protocol biopsies were performed. Immunosuppression was calcineurin inhibitor-based in 90 patients, sirolimus-based in 4 patients and one patient had no anti-rejection therapy (operationally tolerant recipient). Results: The mean time from transplantation to study was 85 months (range 6-248 months). Overall, AHA were found in 23/95 (24.2%) of patients (5 had anti-class I alone, 13 anti-class II alone, and 4 had both anti-class I and II). However, only 4/95 patients (4.2%) had donor-specific antibodies (DSA) (one anti-class I and 3 anti-class II). Twenty-one out of 95 patients (22.1%) had a history of past or current biopsy-proven or radiological biliary complications (chronic rejection, ischemic cholangitis, ischemic type biliary lesions or biliary anastomosis stricture). Among patients with AHA, 4/23 (17,4%) had biliary complications, while it was 17/72 (23.6%) in patients without AHA (NS). Among patients with DSA, 3/4 (75%) had biliary complications (two with biopsy-proven chronic rejection in association with biliary strictures and one with ischemic cholangitis following hepatic artery thrombosis), versus 1/19 (5.3%) patients with AHA but no DSA (p = 0.009), versus 16/72 (22.2%) patients without AHA (p = 0.046). In patients with DSA, immunosuppression was not different than in patients without DSA. Conclusions: We found a 24% AHA prevalence. The presence of DSA, but not of AHA, was significantly associated with an increased incidence of biliary complications including chronic liver allograft rejection. The exact mechanisms and possible causal relationship linking DSA to biliary complications remain to be studied. Larger prospective trials are thus needed to further define the role of AHA and in particular of DSA after liver transplantation.

The presence of a CD4(+) CD25(high) CD45RO(+) CD127(high) T cell population correlates with the clinical status of kidney transplant recipients

Introduction: Recent data have suggested that a population of CD4+ CD25high T cells, phenotypically characterized by the expression of CD45RO and CD127, is significantly expanded in stable liver and kidney transplant recipients and represents alloreactive T cells. We analyzed this putative new alloreactive cellular marker in various groups of kidney transplant recipients. Patients & methods: Flow cytometry was used to analyze the expression of CD25, CD45RO and CD127 on peripheral CD4+ T cells. Of 73 kidney transplant recipients, 59 had a stable graft function under standard immunosuppressive therapy (IS), 5 had biopsy-proven chronic humoral rejection (CHR), 8 were stable under minimal IS and one was an operationally "tolerant" patient who had discontinued IS for more than 3 years. Sixty-six healthy subjects (HS) were studied as controls. Results: Overall, the alloreactive T cell population was found to be significantly increased in the 73 kidney recipients (mean ± SE: 15.03 ± 1.04% of CD4+ CD25high T cells) compared to HS (5.93 ± 0.39%) (p<0.001). In the 5 patients with CHR, this population was highly expanded (31.33 ± 4.16%), whereas it was comparable to HS in the 8 stable recipients receiving minimal IS (6.12 ± 0.86%), in 4 patients who had been switched to sirolimus (4.21 ± 0.53%) as well as in the unique "tolerant" recipient (4.69%). Intermediate levels (15.84 ± 0.93%) were found in the 55 recipients with stable graft function on standard CNI-based IS. Regulatory T cells, defined as CD4+CD25high FoxP3+ CD127low, were found to be significantly reduced in all recipients except in those with minimal or no IS, and this reduction was particularly striking in recipients with CHR. Conclusion: After kidney transplantation, an alloreactive T cell population was found to be significantly expanded and it correlates with the clinical status of the recipients. Interestingly, in stable patients with minimal (or no) IS as well as in patients on sirolimus, alloreactive T cells were comparable the healthy controls. Measuring circulating CD4+CD25high CD45RO+ CD127high T cells may become a useful monitoring tool after transplantation.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Stored blood - an effective immunosuppressive method for transplantation of kidneys from unrelated donors: An 11-year follow-up

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P<0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that tranfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft

Lamivudine therapy for hepatitis B in renal transplantation

Antiviral therapies are associated with an increased risk of acute rejection in transplant patients. The aim of the present study was to evaluate the efficacy and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal transplant patients. Six patients were included in this study. They received 150 mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood cyclosporine levels. The HBV DNA became undetectable in four patients as early as in the third month of treatment. After six months, the viral load was also negative in the other two patients, and remained so until 18 months of follow-up. The medication was well tolerated with no major side effects. Lamivudine was safe and effective in blocking HBV replication in renal transplant patients without any apparent increase in the risk of graft failure for the 24-month period of study.

Preservation of graft function in low-risk living kidney transplant recipients treated with a combination of sirolimus and cyclosporine

The use of sirolimus (SRL) in combination with full doses of cyclosporin A (CsA) results in reduced one-year kidney allograft function, which is associated with shorter long-term allograft survival. We determined the effect of reduced CsA exposure on graft function in patients receiving SRL and prednisone. Ninety recipients of living kidney transplants receiving SRL (2 mg/day, po) were compared to 35 recipients receiving azathioprine (AZA, 2 mg kg-1 day-1, po). All patients also received CsA (8-10 mg kg-1 day-1, po) and prednisone (0.5 mg kg-1 day-1). Efficacy end-point was a composite of biopsy-confirmed acute rejection, graft loss, or death at one year. Graft function was measured by creatinine, creatinine clearance, and graft function deterioration between 3 and 12 months (delta1/Cr). CsA concentrations in patients receiving SRL were 26% lower. No differences in one-year composite efficacy end-point were observed comparing SRL and AZA groups (18 vs 20%) or in the incidence of biopsy-proven acute rejection (14.4 and 14.3%). There were no differences in mean ± SD creatinine (1.65 ± 0.46 vs 1.60 ± 0.43 mg/dl, P = 0.48) or calculated creatinine clearances (61 ± 15 vs 62 ± 13 ml/min, P = 0.58) at one year. Mean ± SD delta1/Cr (-11 ± 17 vs -14 ± 15%, P = 0.7) or the percentage of patients with >20% (26 vs 31%, P = 0.6) or >30% delta1/Cr (19 vs 17%, P = 1) did not differ between the two groups. The use of 2-mg fixed oral doses of SRL and reduced CsA exposure was effective in preventing acute rejection and preserving allograft function.

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13% of the patients. Patients also received azathioprine (2 mg kg-1 day-1, N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg-1 day-1, N = 148). Mean time on dialysis was 79 ± 41 months, 12% of the cases were re-transplants, and 21% had panel reactive antibodies >10%. In 43% of donors the cause of death was cerebrovascular disease and 27% showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60%, respectively. Mean time to last dialysis and to nadir creatinine were 18 ± 15 and 34 ± 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 ± 0.50 mg/dL (DGF 1.68 ± 0.65 vs SGF 1.67 ± 0.66 vs immediate graft function (IGF) 1.41 ± 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22% (DGF 31%, SGF 10%, IGF 8%). One-year patient and graft survival was 92.6 and 78.4%, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0%, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.