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After kidney transplantation, occurrence of anemia in the early post-transplant period (1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single-center study to assess whether delivery of high doses of erythropoietin-stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post-transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety-nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post-transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged50 years, being a recipient aged50 years, not treated for hypertension at pretransplant, and no post-transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post-transplant.

Rituximab off-label use includes organ transplantation. We review the occurrence of infectious disease and its outcome after rituximab therapy. Between April 2004 and August 2008, 77 kidney-transplant patients received rituximab therapy [2-8 courses (median 4) of 375 mg/m2 each] for various reasons. Their results were compared with a control group (n=902) who had received no rituximab. After a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. The incidence of bacterial infection was similar between the two groups, whereas the viral-infection rate was significantly lower, and the rate of fungal infection was significantly higher in the rituximab group. Nine out of 77 patients (11.68%) died after rituximab therapy, of which seven deaths (9.09%) were related to an infectious disease, compared to 1.55% in the controls (p=0.0007). In the whole population, the independent predictive factors for infection-induced death were the combined use of rituximab and antithymocyte-globulin given for induction or anti-rejection therapy, recipient age, and bacterial and fungal infections. After kidney transplantation, the use of rituximab is associated with a high risk of infectious disease and death related to infectious disease.

International audience; Hepatitis E virus (HEV) infection was thought to be responsible for acute hepatitis that did not become chronic. However, we have recently reported that HEV infection can evolve to chronic hepatitis, at least in solid-organ transplant patients. We report on two cases of rapidly progressive of HEV-related cirrhosis that occurred in two organ-transplant patients. Case 1: A kidney-pancreas-transplant patient developed acute HEV hepatitis 60 months after transplantation, which evolved to chronicity as defined by persisting elevated liver-enzyme levels and positive serum HEV RNA. At 22 months after the acute phase, she presented with cirrhosis and portal hypertension, that is ascites and esophagus varices. Case 2: A kidney-transplant patient developed acute hepatitis 36 months after transplantation, which persisted and remained unexplained for 38 months. Then, HEV RNA was searched for in their serum and stools, and was found to be positive in both. Retrospective analysis of available stored serum, mainly the serum obtained at the acute phase, confirmed the diagnosis of chronic hepatitis E. In both cases, a liver biopsy showed cirrhosis. We conclude that HEV infection cannot only evolve to chronic hepatitis, but can also be responsible for rapidly progressing cirrhosis in organ-transplant patients.

Resume Les bacteries sont les microorganismes les plus frequemment impliques dans les infections du patient transplante, le pronostic etant variable selon l’agent concerne et le contexte de survenue. Il existe deux cadres distincts qui exposent les malades a des risques relativement specifiques et entrainent des attitudes preventives differentes : la greffe de cellules souches hematopoietiques et les transplantations d’organes solides. Lors des greffes de cellules souches hematopoietiques, la neutropenie, la presence de voies veineuses centrales a demeure, et la survenue de maladie du greffon contre l’hote constituent les elements majeurs du risque d’infection bacterienne. L’evolution des regimes de conditionnement et des strategies de greffe vise a controler ce risque. Apres les transplantations d’organes solides, les infections bacteriennes surviennent principalement dans un contexte postoperatoire, favorisees par les dispositifs medicaux. L’amelioration des techniques chirurgicales joue un role decisif dans la maitrise de ces complications infectieuses. Quel que soit le type de greffe, les bacteries habituellement rencontrees sont des germes couramment isoles dans un environnement hospitalier. D’autres presentent un caractere opportuniste et leur pathogenicite depend etroitement de l’etat global d’immunodepression du patient, faisant du transplante un terrain particulierement fragile par rapport a ces bacteries. Dans tous les cas, la rapidite du diagnostic bacteriologique conditionne le pronostic du patient, dans la mesure ou l’antibiotherapie doit etre adaptee dans les meilleurs delais.

International audience; Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.

The aims of the present study were to assess the incidence of cytomegalovirus (CMV) reactivation, and to determine the predictive factors for CMV reactivation in CMV seropositive kidney-transplant patients. One hundred ninety CMV seropositive kidney-transplant patients were included in this study; of these, 39 patients had received CMV prophylaxis. CMV DNAemia was assessed by real-timepolymerase chain reaction assay every 2 weeks until day 120, then every 3–4 weeks until day 180, and then every month until day 365. One hundred seven patients (56.3%) had at least one positive CMV DNAemia within the first year. The time between renal transplantation and the first positive CMV DNAemia was 59 ± 5 days. The number of positive CMV DNAemia/patient was 3.28 ± 0.22. CMV viral load at first positive CMV DNAemia was 704 (10–742,000) copies/ml. The donor CMV seropositivity, the absence of CMV prophylaxis, and the occurrence of acute rejection before CMV reactivation were independent factors associated with CMV reactivation within the first year after kidney transplantation. Hence, CMV reactivation is frequent after kidney transplantation. CMV prophylaxis in CMV seropositive kidney-transplant patients should be offered to avoid CMV-related side-effects. J. Med. Virol. 80:1012–1017, 2008. © 2008 Wiley-Liss, Inc.

A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.

Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study.Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation.A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin.An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.

International audience; RATIONALE: Ethanol rapidly eradicated experimental biofilm. Clinical studies of ethanol lock to prevent catheter-related infections (CRIs) suggest preventive efficacy. No such studies have been done in intensive care units (ICU).OBJECTIVES:To determine whether ethanol lock decreases the risk of major CRI in patients with short-term dialysis catheters (DCs).METHODS:A randomized, double-blind, placebo-controlled trial was performed in 16 ICUs in seven university hospitals and one general hospital in France between June 2009 and December 2011. Adults with insertion of a nontunneled, nonantimicrobial-impregnated double-lumen DC for an expected duration greater than 48 hours, to perform renal-replacement therapy or plasma exchange, were randomly allocated (1:1) to receive a 2-minute catheter lock with either 60% wt/wt ethanol solution (ethanol group) or 0.9% saline solution (control group) at the end of DC insertion and after each renal-replacement therapy or plasma exchange session. The main outcome was major CRI defined as either catheter-related clinical sepsis without bloodstream infection or catheter-related bloodstream infection during the ICU stay.MEASUREMENTS AND MAIN RESULTS:The intent-to-treat analysis included 1,460 patients (2,172 catheters, 12,944 catheter-days, and 8,442 study locks). Median DC duration was 4 days (interquartile range, 2-8) and was similar in both groups. Major CRI incidence did not differ between the ethanol and control groups (3.83 vs. 2.64 per 1,000 catheter-days, respectively; hazard ratio, 1.55; 95% confidence interval, 0.83-2.87; P = 0.17). No significant differences occurred for catheter colonization (P = 0.57) or catheter-related bloodstream infection (P = 0.99).CONCLUSIONS:A 2-minute ethanol lock does not decrease the frequency of infection of DCs in ICU patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00875069).

Introduction The aim of this retrospective study was to determine the outcome of third cadaveric renal transplantations performed between 1989 and 2004 among a cohort of 35 patients whose immunosuppression included induction therapy and calcineurin inhibitors. Most patients were highly sensitized with 1 (0–4) HLA (classes I + II) incompatibility between donor and recipient. Results The median follow-up time was 57 months (range, 1–190). Fourteen patients experienced delayed graft function that required posttransplantation hemodialysis. The current patient and graft survival rates were 91.4% and 82.8%, respectively. At last follow-up, 6 grafts had been lost: 1 due to primary nonfunction; 1 due to an urinary leak (day 45); 2 deaths with functioning grafts; and 2 chronic allograft nephropathies (CAN) at 85 and 60 months posttransplantation, respectively. Among the 10 patients who experienced acute rejection episodes, half were steroid-sensitive, whereas the others required OKT3 therapy. Overall, when excluding the 2 patients who presented with early loss of their grafts, 13 of 33 patients (39.4%) developed CAN, which led to the graft loss in only 2 cases. The mean creatinine clearance was 57 ± 23 mL/min at year 5. Of the 35 recipients, 12 (34.3%) developed graft/perigraft complications, among whom 10 (83.3%) required treatment. The most frequent complication was lymphocele (M = 4; 11.4%) or infections that led to rehospitalization (n = 17). Conclusion Results from third transplantations were encouraging. Thus, despite the organ shortage, a third graft was worth it!

Background. The aim of our study was to identify the independent factors that might predict anemia at 6 (M6) and 12 (M12) months posttransplantation. Methods. Postrenal transplant anemia (PTA) was defined as having a hemoglobin (Hb) level below 13 g/dl for men and below 12 g/dL for women. In this study, we included all the recipients who received a renal transplant in 2001 at our department, and for whom the graft was still functioning 1 year later (n=92). Results. Anemia was observed in 78%, 35.5% and 25% of patients at day (D)0 and at M6 and M12, respectively. Iron deficiency was found in 14% of patients at DO and in 13% of patients at M12. A total of 59.8% of patients had received at least one blood transfusion in the postoperative period, whereas 41.3% of patients had received recombinant erythropoietin (rEpo) therapy within the first months posttransplantation. In multivariate analysis, the independent predictive factors of anemia at M6 were Epo level at DO, initial nephropathy (polycystic kidney disease vs. others), posttransplantation rEpo therapy, hematocrit at M3, platelets at D7, and sirolimus therapy. The independent predictive factors of anemia at M12 were Epo level at DO, platelets at D7, delayed graft function (DGF), creatinine clearance at M12, serum creatinine at M12, and Hb level at M6. Conclusions. The prevalence of PTA was 25% at M12. DGF, renal function at M12, and anemia at M6 were independent risk factors for still having anemia at M12.

Background: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. Methods: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins®; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 ± 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. Results: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. Conclusion: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.

To the Editor: A man, 56 years of age, was admitted to the hospital for epigastric pain, fever, and fatigue 8 years after a cardiac transplant. His immunosuppressive regimen consisted of cyclosporine A, mycophenolate mofetil, and steroids. Clinical examination revealed a 4-kg weight loss within 3 months without peripheral lymph node enlargement. Laboratory test results showed moderate anemia, severe lymphopenia, and moderately increased C-reactive protein. Serologic results for HIV, Brucella spp., Coxiella burnetii, and Francisella tularensis were negative. Whole-body computed tomography scanning showed enlarged mediastinal and abdominal lymph nodes. Bone marrow histopathologic results ruled out lymphoma or granuloma but showed a histiocytic infiltrate and intracellular acid-fast bacilli (AFB) with positive Ziehl–Neelsen staining. Sputum, urine, gastric aspirates, and bronchoalveolar lavage specimens revealed no AFB. A mediastinal lymph node biopsy showed few AFB, suggesting M. tuberculosis or nontuberculous mycobacteria. Isoniazid, rifampin, ethambutol, and clarithromycin were prescribed for 2 months, followed by rifampin, ethambutol, and clarithromycin. Cultures for mycobacteria remained negative. Five months after treatment initiation, the patient experienced severe abdominal pain, diarrhea, and continued weight loss. Lymph node biopsy was repeated; results showed intramacrophagic coccobacilli tinted with Ziehl-Neelsen, Gram, and periodic acid–Schiff (PAS) stains. Two diagnoses were considered: malakoplakia and Whipple disease (WD). Screening results from quantitative real-time PCR (qPCR) for Tropheryma whipplei were negative for blood, saliva, stools, urine, and lymph nodes. Although no characteristic Michaelis–Gutmann bodies were seen, the staining characteristics of the intracellular coccobacilli were compatible with Rhodococcus equi, a pathogen associated with malakoplakia. Combined treatment with ertapenem, teicoplanin, and amikacin was implemented but failed to induce clinical improvement. Culture of the biopsy specimen failed to grow R. equi or mycobacteria, and the result of 16S rRNA PCR was negative. To investigate the cause of the diarrhea, the patient underwent endoscopy, which showed a thickened duodenal wall. A duodenal biopsy specimen displayed a massive histiocytic infiltrate, with positive PAS and Gram staining but negative Ziehl-Neelsen staining. Cultures remained negative for mycobacteria. Acting on the hypothesis of WD, we administered doxycycline and hydroxychloroquine for 4 weeks, then discontinued for ineffectiveness. Four weeks after cessation of antimicrobial drug treatment, a third lymph node biopsy was performed, in which the T. whipplei PCR result was positive. Antibacterial drug treatment for WD was resumed, but the patient’s condition worsened. Simultaneously, extracted DNA and fresh tissue of all biopsy specimens were sent to the Unite de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, (Marseille, France), a reference laboratory for WD. Immunohistochemical analysis, DNA extraction, and T. whipplei qPCR were performed as described (1,2). Biopsy specimens were subjected to a systematic molecular approach, which included 16S rRNA PCR and several specific PCRs (3) (Table A1). Histopathologic results of the duodenal biopsy revealed PAS-positive and diastase-resistant macrophages (Figure) with faint immunohistochemical staining. Results of T. whipplei PCRs targeting 2 different sequences were negative for the duodenal and lymph node biopsy specimens. These specimens were also negative by PCR for 16S rRNA, Bartonella spp., and F. tularensis. Conversely, Ziehl–Neelsen staining showed numerous AFB. Results of PCRs were negative for M. tuberculosis and M. avium but positive for Mycobacterium spp. Figure Duodenal biopsy specimen from the patient with posttransplant cachexia. Ziehl–Neelsen acid staining of a patient biopsy specimen, showing partially reduced villous architecture at low magnification, with numerous Ziehl–Neelsen-positive ... Sequencing facilitated identification of Mycobacterium genavense (99.6% of homology with the isolate with GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"HM022216","term_id":"295815632","term_text":"HM022216"}}HM022216). Combined treatment with amikacin, rifabutin, moxifloxacin, clarithromycin, and ethambutol was implemented. To enhance the chances of eradicating M. genavense, mycophenolate mofetil was discontinued and cyclosporine A reduced. The patient’s condition was largely unimproved; clinical improvement was observed 9 months after treatment reinitiation. Cardiac allograft function remained unaltered. Optimal duration of therapy is unknown; treatment had been ongoing for nearly 12 months at time of publication. More than the choice of antimycobacterial agents, we believe that it is the reduction in immunosuppression and the duration of therapy that eventually facilitated clinical improvement. M. genavense is a slow-growing, nontuberculous mycobacterium that infects immunocompromised hosts (4). Only 3 cases of M. genavense infection in solid-organ transplant recipients have been reported (5–7). M. genavense has a predilection for the digestive tract, which explains the severity of the gastrointestinal symptoms (4). Moreover, it can mimic the endoscopic and histopathological features of WD (8). In this case, the positive PAS-staining, the weak positivity of immunochemical staining for T. whipplei, and the false-positive results for 1 PCR temporarily delayed diagnosis. False-positive PCR results have been mainly reported when molecular diagnosis for T. whipplei was based on 16S rRNA PCR (9). Thus, positivity of a first PCR should be confirmed by using a second PCR with another target (10). Bacteria responsible for lymph node enlargement are rarely isolated by culture. Molecular methods performed on lymph node biopsy specimens are useful diagnostic tools, but the common single molecular approach using 16S rRNA PCR lacks sensitivity, which delayed diagnosis for this patient (3). To address this issue, simultaneously to performing 16S rRNA PCR, we followed a strategy of systematic qPCR for lymph node specimens that targeted Bartonella spp., F. tularensis, T. whipplei, and Mycobacterium spp (3). This report confirms the power of this systematic molecular approach, which enabled us to identify a rare bacterial agent scarcely reported for transplant patients.

International audience; Early antifungal therapeutic strategies are proposed during invasive fungal infection (IFI), but antifungal stewardship programs should institute a systematic reevaluation of prescriptions, particularly in the context of empirical treatment. Here, we aimed to evaluate the performances and particularly the negative predictive value (NPV) of diagnostic strategies, including a whole blood panfungal quantitative PCR assay (PF-qPCR) in a high risk population for IFI. The first step was to standardize and optimize a new PF- rtPCR targeting ITS2 region. Then, this method was evaluated in a multicenter prospective study including 313 patients with suspected IFI for whom an early antifungal treatment was prescribed. All patients enrolled at day 0 of their treatment benefited from serum Aspergillus galactomannan (GM) antigen detection twice a week, weekly PF-qPCR assay, and when indicated and feasible, CT-scan and mycological sampling. In total, 125 of 313 patients were diagnosed with IFI: 68 invasive aspergillosis (eight proven, 48 probable and 12 possible), one fusariosis, 47 candidemia, three disseminated candidiasis and six cryptococcosis. Globally, the sensitivity of the PF-qPCR assay was only 40%, but the specificity, PPV and NPV were 96%, 88% and 69%, respectively. In the population of patients at high risk for invasive aspergillosis who also benefited from Aspergillus GM detection, the sensitivity and the NPV of the combined detection reached to 78% and 84%, respectively. Even higher NPV were obtained when combining negative PF-qPCR and CT scan (95%) as well as negative GM and CT scan (93%), thus allowing to rationalize and re-evaluate the prescription of empirical treatment in such highly selected population.

International audience; Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60 ± 48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109 ± 48 months after liver transplantation. eGFR decreased from 92 ± 33 mL/min at transplantation to 63 ± 19 mL/min after six months, to 57 ± 17 mL/min at the kidney biopsy, to 54 ± 24 mL/min at last follow-up (p < 0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR ≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.

International audience; Ochroconis gallopava is an emerging cause of mycosis in solid organ transplant recipients. Herein, we report a rare case of disseminated O. gallopava infection that involved lung, subcutaneous area, brain and peritoneum in a heart transplant recipient. Despite voriconazole therapy, the patient died 2 months after diagnosis.

Objectives This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients. Materials and methods From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant. Results After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effects were reported in 134 patients (89.3%). They included (1) hospitalization for infection (n=52), (2) de novo proteinuria (n=40), and (3) eight patients with biopsy-proven acute rejection. Sirolimus was stopped and replaced by calcineurin inhibitors in 37 patients after a mean of 16 months treatment. After stopping sirolimus, renal-allograft function remained stable at 2 years. Conclusions Conversion of calcineurin inhibitors to sirolimus in kidney transplant recipients was associated with improved renal function. The reintroduction of calcineurin inhibitors was safe in patients who were withdrawn from sirolimus owing to adverse effects.

INTRODUCTION The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs. MATERIALS AND METHODS Thirty-two patients, who experienced an early graft loss (

Background Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist. Methods We assessed kidney function and histology in solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels. Results During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance. Conclusion HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.

Paecilomyces lilacinus is an emerging pathogen in immunocompromised patients. We report here a case of cutaneous hyphomycosis in a 63-year-old heart transplant recipient caused by the simultaneous presence of 2 molds: Paecilomyces lilacinus and Alternaria alternata. The infection was successfully treated with local voriconazole followed by oral terbinafine.

Background There are substantial differences in the risk evaluation, clinical presentation, and outcome of Pneumocystis pneumonia between human immunodeficiency virus (HIV)-positive and HIV-negative immunocompromised patients. To compare the host immune defenses against Pneumocystis jirovecii, the blood and alveolar lymphocyte profile was explored in these 2 populations. Methods The total, CD3(+), CD4(+), and CD8(+) T-lymphocyte counts were measured in the blood and alveoli of immunocompromised patients with a P. jirovecii DNA detected in their bronchoalveolar lavage samples, according to their HIV status. Results In blood and alveoli, the CD4(+) and CD8(+) T-lymphocyte counts were higher and lower, respectively, in the HIV-negative group. The threshold for initiating prophylaxis in HIV-positive persons, 200 CD4(+) T cells/μL, was not pertinent for HIV-negative patients. The P. jirovecii burden correlated with the blood CD4(+) T-cell counts in the HIV-positive but not in the HIV-negative group. Nevertheless, whatever the HIV status, a correlation was observed between alveolar CD4(+) T cells and the P. jirovecii burden. Conclusions The T-lymphocyte profile was different between HIV-positive and HIV-negative patients with P. jirovecii, suggesting a distinct pathogenesis. Alveolar CD4(+) T cells could be critical to explain the development of Pneumocystis pneumonia but may also be important for evaluation of disease risk, mostly among HIV-negative immunocompromised patients.

Chronic kidney disease is a common complication after liver transplantation. However, few reports regarding kidney histology exist for this setting.Inulin clearance was measured and a kidney biopsy was performed in 99 patients at 60 ± 48 months after liver transplantation. Kidney biopsies were scored according to the Banff classification, and interstitial fibrosis was measured by a computerized quantitative method.There was a steep decrease in kidney function within the first 6 months following transplantation, but this lessened thereafter. At kidney biopsy, inulin clearance and estimated glomerular filtration rate (eGFR) (using the abbreviated Modification of Diet in Renal Disease equation) were highly correlated (r(2) = 0.47, P0.0001). A decrease in eGFR at 6 months post-transplant was the sole predictive factor for inulin clearance of60 mL/min/1.73 m(2) at 5 years post-transplant. Few patients had a specific pattern of kidney histopathology and all patients had complex primary lesions. Lowered eGFR at 6 months post-transplant was a predictive factor for50% sclerotic glomeruli on the kidney biopsy. The duration of tacrolimus therapy, as compared to cyclosporine A, was a protective factor for20% interstitial fibrosis on the kidney biopsy.In the setting of liver transplantation, this is the largest kidney-histology study to confirm that histological kidney lesions are complex, multiple and interrelated. Kidney function at 6 months post-transplant can predict long-term kidney function and histology.

The objective of this study was to describe the renal and extrarenal findings in patients with recessively inherited familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) associated with CLDN19 mutations.Medical records of three patients from two French unrelated families with CLDN19 mutations were retrospectively examined.Direct sequencing of CLDN19 identified a known variant (p.Gly20Asp) in all patients and a new missense mutation (p.Val44Met) in one (compound heterozygous). The patients' renal phenotype closely mimicked CLDN16-related nephropathy: low serum Mg2+ (0.65 mmol/L) despite oral supplementation, hypercalciuria partly thiazide-sensitive, and progressive renal decline with ESRD reached at age 16 and 22 years in two individuals. Primary characteristics (failure to thrive, recurrent urinary tract infections, or abdominal pain), age at onset (0.8 to 16 years), and rate of renal decline were highly heterogeneous. Ocular involvement was identified in all patients, although two patients did not have visual loss. Additionally, exercise intolerance with pain, weakness, and electromyographical alterations mimicking a Ca2+/K+ channelopathy (pattern V) were observed in two of three individuals. These features persisted despite the normalization of serum K+ and Mg2+ after renal transplantation.Ocular manifestations, even subtle, and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that need to be searched for in patients with FHHNC and may indicate CLDN19 mutations.

This sequential study evaluated two strategies regarding human cytomegalovirus (HCMV) infection/disease in HCMV-seropositive de novo kidney-transplant patients. The first cohort of patients (group 1; n = 132) was monitored sequentially for HCMV DNAemia; if it was positive (a cut-off at 3 log(10) copies/ml), the patient was given pre-emptive IV ganciclovir therapy (10 mg/kg/day for 3 weeks). The second cohort consisted of 150 patients (group 2) who were given valganciclovir (VGC) prophylaxis (900 mg/day) for the first 3 months posttransplantation. During the mean follow-up of at least 2 years for both cohorts, VGC prophylaxis resulted in a significant decrease in both CMV infection (68.9% vs. 33.3%; P0.001) and disease (9.8% vs. 2.68%, P = 0.021). Factors associated with HCMV reactivation in multivariate analysis were (i) no HCMV prophylaxis; (ii) recipient's age; (iii) being placed on ciclosporine A and mycophenolic acid from the beginning of transplantation (iv) donor HCMV-seropositivity; and (v) being a male recipient. No cases of ganciclovir resistance were detected in the prophylactic group. HCMV prophylaxis had no impact on 2-year patient/graft survival or on kidney-allograft function. We conclude that VGC-prophylaxis can be reasonably used to treat HCMV-seropositive kidney-transplant recipients.

Background & Aims Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients. Pegylated α-interferon can effectively treat chronic HEV infection after liver transplantation but is contraindicated for kidney transplantation. We assessed the antiviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation. Methods In a pilot study performed at Toulouse University Hospital, 6 patients that received kidney transplants who were positive for HEV RNA (infected with HEV for 36.5 months; [range, 11–46 months]) were given ribavirin monotherapy for 3 months. Ribavirin was given at 600–800 mg/day in 2 separate doses, based on the patient's ability to clear creatinine. Results Median serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range, 4.35–7.35 log copies/mL). Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients. A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended. At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase. Anemia was the main side effect caused by ribavirin therapy. Conclusions Ribavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections. Further studies are required to determine the optimal duration of ribavirin therapy.

Background Hepatitis-E virus (HEV) infection can be responsible for chronic hepatitis in solid-organ transplant patients. Methods We identified 33 cases of autochthonous acute HEV infection in solid-organ transplant patients. Results Among 27 HEV-positive patients, who had a follow-up of more than 6 months, 16 (59.25%) evolved to chronic HEV infection, defined by persisting elevated liver-enzyme levels and positive serum HEV RNA 6 months after diagnosis. Serial liver biopsies showed progression in liver activity and liver fibrosis. Three patients developed liver cirrhosis. The proportion of patients receiving tacrolimus compared with cyclosporine A was significantly higher in patients who evolved to chronic disease. Immunosuppressive therapy was reduced in patients with chronic hepatitis; however, those who had a dramatic decrease in tacrolimus trough levels were more likely to clear the virus. Four chronic liver transplant patients were cleared off the virus at 14, 16, 22, and 23 months after diagnosis. At last follow-up, their tacrolimus trough levels and daily steroid doses were significantly lower than those who remained viremic. These four patients had lower liver-enzyme levels and lower activity scores on liver biopsies, and their peripheral blood CD3- and CD4-positive cell counts were also significantly higher. Conclusions The rate of chronic HEV-related hepatitis is approximately 60% in solid-organ transplant patients. When possible, the reduction of immunosuppressive drugs targeting T cells should be considered as a first-line therapeutic option.

Summary Tacrolimus-based immunosuppression is the most frequently prescribed immunosuppression for kidney-transplant (KT) patients. Because tacrolimus has a narrow therapeutic window, drug monitoring is mandatory. Of the many methods used to assess whole-blood trough levels, antibody-conjugated magnetic immunoassay (ACMIA) is popular because, compared with microparticle enzyme-linked immunoassays (MEIA), there is no need to pretreat samples, thus reducing time taken by the laboratory technician. Herein, we report on a KT tacrolimus-treated patient who experienced falsely elevated whole-blood tacrolimus concentrations after using the ACMIA method. ACMIA gave trough levels of 24 ng/ml, whereas the actual trough level, when measured by enzyme-multiplied immunoassay technique (EMIT) and high-performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), was nil. After a workup we only found one factor that might have caused the elevated concentration: positive anti-double stranded DNA autoantibodies. We conclude that, when ACMIA produces surprisingly high tacrolimus concentrations in organ-transplant patients, these should be reassessed immediately using either LC-MS/MS or another immunoassay in order to eliminate falsely elevated results.

International audience; BACKGROUND: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d. METHODS: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period. RESULTS: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function. CONCLUSION: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.

International audience; The aim of our study was to assess the efficacy and safety of entecavir in kidney- and liver-transplant recipients with chronic hepatitis B virus (HBV) infection. Ten male transplant patients with chronic HBV infection (eight kidney- and two liver-transplant patients), who have become adefovir (n=9) or lamivudine-resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After a median follow-up of 16.5 months, entecavir therapy was associated with a significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10 copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-) patients. There were no significant changes in renal function or hematological parameters. This study demonstrates that entecavir therapy is safe and efficient in HBV(+) organ-transplant patients.

We report on three cases of severe disseminated Herpes simplex type-2 (HSV-2) infection that occurred in two orthotopic liver-transplant (OLT) and one renal-transplant patients. In two cases, i.e., in the OLT patients, this was associated with HSV-2-related acute hepatitis. The rapid onset of IV acyclovir (ACV) therapy led to recovery within 8-12 days. Although rare, HSV-2-disseminated infection, in the context of organ transplantation may be life-threatening, but can be cured if ACV therapy is initiated early in the course of this disease.

Polyomavirus-associated nephropathy (PVAN) affects 1-10% of kidney-transplant (KT) patients, with graft failure/loss in approximately 90% of cases. Reducing immunosuppression is the key treatment option, but addition of leflunomide may improve BK Virus (BKV) clearance and graft survival. In a prospective open-labeled study, 12 KT patients with biopsy-proven PVAN were treated with reduced immunosuppression and leflunomide. BKV viremia and graft function were followed. PVAN was diagnosed at 6 months (3-192) post-transplant; median serum creatinine concentration (sCC) was 189 micromol/l (92-265). After 16 months (8-30) of follow-up, the sCC was 150 micromol/l (90-378, NS). Renal function improved in six cases (50%), remained stable in two (16.6%) and deteriorated in four (33.4%), with graft loss in two (17%). Clearance of BKV viremia was observed in five (42%) cases. Side effects included anemia in six cases leading to leflunomide withdrawal in two patients, and mild thrombocytopenia. In KT patients diagnosed with PVAN, leflunomide plus reduced immunosuppression improved graft function in 66.6%, cleared BKV viremia in 42%, and resulted in side effects in 17%. This limited efficacy contrasts with other reports and falls short of expectation. We conclude that active screening, earlier diagnosis and intervention remain the cornerstones of treatment.

Background. New-onset diabetes mellitus (NODM)—a common complication of kidney transplantation—is associated with increases in graft loss, morbidity and mortality. Methods. This is a purely observational study of 527 patients taking a calcineurin inhibitor (CNI), based on data collected at a single routine visit 6–24 months after kidney transplantation. Diabetes was defined according to ADA/WHO guidelines. Results. The mean age of the patients was 47.2 years and 61.1% were men; 49.5% were receiving cyclosporine microemulsion (CsA-ME) and 50.5% tacrolimus (Tac). NODM developed in 7.0% after a median interval of 1.6 months. In CsA-ME-treated patients, the unadjusted cumulative risks of NODM were 5.5% and 8.4% at 1- and 2-year post-transplantation, while in Tac-treated patients, the risks were respectively 17.4% and 21%. Four independent risk factors (RFs) were identified by multivariate analysis: maximum lifetime body mass index >25 [odds ratio (OR) ¼ 5.1], pre-transplantation impaired fasting glucose (OR ¼ 4.7), hepatitis C status (OR ¼ 4.7) and Tac vs CsA-ME treatment (OR ¼ 3.0). Conclusions. NODM is associated with certain RFs present prior to kidney transplantation, and with treatment with Tac as opposed to CsA-ME.

Mycophenolic acid dose modifications after renal transplantation seem to adversely affect renal allograft outcome. The aim of this retrospective study was to examine the effect of mycophenolic acid dose modifications on renal function 1 year after transplantation and to determine the factors predictive of those dose modifications within the first year after renal transplantation.All 130 patients at our institution who were treated de novo between January 2002 and April 2003 with either a mycophenolate mofetil-based or an enteric-coated mycophenolate sodium-based therapy and who had a functioning renal allograft 1 month after transplantation were included in this study.Fifty-seven patients (43.8%) underwent a dose modification during the first year after transplantation. One, 3, 6, and 12 months after transplantation, renal function was significantly improved in the patients who did not receive a dose modification. A mycophenolic acid dose that 1 year after transplantation was less than the initial dose received just after transplantation was an independent factor associated with deteriorating renal function. Sirolimus immunosuppression, Cytomegalovirus infection, and pretransplant lymphocyte counts were independent factors associated with mycophenolic acid dose modifications within the first year after kidney transplantation.Modification of the mycophenolic acid dose may adversely affect renal function 1 year after transplantation.

The aim of this study was to assess the effects of tacrolimus in combination with either sirolimus (n = 10) or mycophenolate mofetil (n = 7) on renal function and renal histopathologic factors 6 and 12 months after kidney transplantation.Renal function was assessed by the glomerular filtration rate (as measured by the inulin clearance rate) and by determining renal functional reserve. A renal allograft biopsy was performed at the time of transplantation and 6 and 12 months later.Serum creatinine levels tended to be higher in the sirolimus group 12 months after transplantation. In contrast, inulin clearance and renal functional reserve were similar in both groups 6 and 12 months after transplantation. With respect to histopathologic findings, only mononuclear-cell interstitial inflammation was significantly higher in the sirolimus group than in the mycophenolate mofetil group 12 months after transplantation. However, the progression of tubular atrophy, interstitial fibrosis, and vascular fibrous intimal thickening within the first postoperative year was significantly greater in the sirolimus group.In the long term, the addition of sirolimus to treatment with tacrolimus in de novo renal transplant patients might more adversely affect renal allograft survival than might the addition of mycophenolate mofetil to tacrolimus therapy.

Chronic renal failure (CRF) is increasingly prevalent in solid-organ-transplant patients. This is in part related to the long-term use of calcineurin inhibitor (CNI) agents. However, in orthotopic liver-transplant (OLT) patients, the effects of superimposed hepatitis C virus (HCV)-related renal lesions could also be a factor. The aim of this cohort study (February 2000 to September, 2003) was to identify the predictive factors at one year post-transplantation for CRF in OLT patients associated with induction therapies. CRF was defined as having a creatinine clearance (CC) lower than 60 mL/min. Of the 97 transplants performed during that period, 72 were still functioning after one year. Of these, 33 patients (45.8%) had CRF. In univariate analysis, the predicting factors for CRF were recipient sex (female), initial liver disease (HCV-related cirrhosis), pre-transplant CC (80 mL/mn), and post-transplant serum creatinine130 micromol/L at day 3 and months (M) 1, 3, and 6. In multivariate analysis, the independent predictive factors for CRF included female sex [OR: 11.5 (2.3-58.3); p = 0.003], HCV infection [OR: 5.01 (1.1-22.7); p = 0.03], pre-OLT CC80 mL/mn [OR: 5.4 (1.2-23.7); p = 0.025], and serum creatinine at M6 greater than 130 micromol/L [OR: 19.6 (3.7-102.5); p = 0.0004]. Among all of the predictive factors for post-OLT CRF, only one is modifiable: post-transplant serum creatinine, which could be, to some extent, related to the long-term use of CNIs.

To report the results of laparoscopic live donor nephrectomy (LLDN) and to describe our technique.We retrospectively reviewed 47 laparoscopic live donor nephrectomies performed between January 1999 and July 2005. Several parameters were studied: donor clinical characteristics, intraoperative and postoperative complications, operating time and warm ischaemia time. This series comprised 26 women (55.31%) and 21 men (44.68%) with a mean age of 48 +/- 20 years. Donor nephrectomy was mainly performed on the left kidney (85.37%). It was performed by lumbar endoscopy in the first 20 cases and by laparoscopy in 27 cases. Kidney extraction was performed via an incision between two trocar orifices for the first cases and via an iliac incision for the last 18 cases.The mean operating time was 189 min with a mean blood loss of 127 ml. Warm ischemia time was 6 minutes. Open conversion was required in two cases: renal vein injury in one case and an obese donor with difficulties of dissection in the other case. Surgical revision was required in only one case (haemoperitoneum secondary to genital vein injury). A trocar orifice abscess was observed in one case and prolonged ileus was reported in 2 cases. In the recipient, a urinary anastomotic fistula was observed secondary to ischaemic necrosis of the distal segment of the ureter. Late complications were essentially vascular (19.14%). A right renal graft was lost due to an error of compatibility. Mean serum creatinine was 132 +/- 6.5 micromol/l at 3 months for the other recipients.Our experience confirms the feasibility and efficacy of laparoscopic live donor nephrectomy. Intraoperative and postoperative complications and the conversion rate were low. Renal function was rapidly restored in the recipient. The morbidity of this technique is low, but there is a high risk of vascular complications at the beginning of the operator's experience.

The aim of our study was to prospectively assess 1-year allograft outcomes and the evolution of lymphocyte subsets in a group of renal transplant patients who had received intraoperative rabbit antithymocyte antibodies (RATG).We compared 1-year allograft transplant outcomes in renal transplant recipients who had received intraoperative RATG (group 1, n=53) with the outcomes observed in patients in a historical control group who had received postoperative RATG (group 2, n=49). RATG were given at the same dosage (1 mg/kg) during the first 3 days, and then the dosage was adapted according to CD2 count, until calcineurin inhibitors were started.The overall dosage of RATG administered was significantly lower in group 1. At day 4, CD2, CD3, and CD19 T-cell subset counts were significantly higher in patients in group 1. From 3 months after transplantation, CD4/CD8 ratios were significantly lower in patients in group 1 because of a rapid regeneration of CD8 T cells. One-year total lymphocyte counts were significantly higher in patients in group 1. There were fewer severe infectious complications in patients in group 1. One-year renal function was better in patients in group 2. Donor age was the only independent factor associated with renal function at both 1 month and 1 year after transplantation.When RATG are infused intraoperatively, a lower total amount of RATG is required to prevent acute rejection as compared with postoperative RATG infusion. Consequently, fewer serious lymphopenia-associated complications are observed during the first year after transplantation.

Background. Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of our prospective questionnaire-based study was to assess GI side-effects in de novo renal-transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). Methods. Between January 2002 and April 2003, all patients receiving MPA with a functioning allograft at 1 month post-transplantation were enrolled in this study (n ¼ 130). Ninety-three of them received MMF (group I), and 37 patients received EC-MPS (group II). Each month, every patient completed a questionnaire regarding GI disorders. Results. During the first year post-transplantation, GI disorders occurred in 31 patients from the MMF group (33.3%) and 12 patients from the EC-MPS group (32.4%) (not significant). The incidence of upper GI disorders was also similar in both groups. Diarrhoea was observed in 18 patients (19.3%) from group I, and in five patients from group II (13.5%) (not significant). Its frequency and severity were similar in both groups. Weight loss was observed in three patients receiving MMF. Diarrhoea resolved spontaneously in 10 patients from group I and in all patients from group II. For the other eight patients in group I, the diarrhoea required MMF discontinuation in three patients and dose reduction in five patients. Conclusions. In conclusion, in this questionnaire-based evaluation, the incidence of GI disorders was similar in patients receiving either MMF or EC-MPS during the first year post-transplantation.

Objective The aim of our study was to identify independent factors that might predict anemia at 6 months' (M6) and 12 (M12) months' posttransplantation. Postrenal transplant anemia was defined as a hemoglobin (Hb) level below 13 g/dL for men, and below 12 g/dL for women. We included 99 renal transplants performed in our department in 2001, for whom the graft was still functioning at 1 year. Results Anemia was observed in 78%, 35.5%, and 25% on day (D) 0, and at M6, and M12, respectively. Iron deficiency was observed in 14% of patients at D0, and 13% at M12. During the postoperative period, 59.8% of patients received at least one blood transfusion, whereas 37% of patients were prescribed recombinant erythropoietin (rEpo) therapy within the first few months posttransplantation. By multivariate analysis the independent predictive factors for anemia at M6 were rEpo therapy at D0, initial nephropathy, posttransplantation rEpo therapy, hematocrit at M3, platelets at D7 and sirolimus therapy. The independent predictive factors for anemia at M12 were rEpo therapy at D0 and platelets at D7, delayed graft function (DGF), serum creatinine, and creatinine clearance at M12, and Hb level at M6 were also checked. Conclusion The prevalence of anemia is 25% at M12; DGF, renal function at M12, and anemia at M6 were independent risk factors of anemia at M12.

Background Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). However, in recent years, the long-term results of OLT in this setting are worsening, possibly due to the powerful immunosuppressants in use. The aim of our study was to assess the safety and efficacy of induction therapy using rabbit antithymocyte globulin antibodies (RATG). Methods Over an 18-month period from January 2000 to June 2001, 16 patients underwent OLT for HCV-related ESLD and survived more than 1 month posttransplantation. They received induction therapy based on RATG (Thymoglobulins, Sangstat, France) at 1 mg/kg per day for 3 consecutive days, and it was then adjusted to maintain a CD2 count below 50/mm3. Overall, RATG was given for a median of 5 days for a total dose of 406 ± 45 mg. Steroids were started pretransplant and tacrolimus on day 1. The primary end-points were patient and graft survivals at 6 months posttransplantation, incidence of rejection, infectious complications (bacterial, viral, and fungal) and recurrence of HCV infection based on biochemical, virological, and histologic criteria. Results The survival rates were 100% for patients and 93.7% for grafts. The acute rejection rate was 37.5%. The median time to acute rejection was 15.5 days. There was only one serum sickness case. Cytomegalovirus infections occurred in 25% of patients. The rate of de novo diabetes that required insulin therapy was at 50%. The rate of HCV recurrence was 56.25%. In addition, HCV RNA serum concentrations increased significantly posttransplantation (>1 log). In conclusion, RATG induction therapy is safe and efficient in HCV-positive liver recipients.

BACKGROUND Treatment with trisodium citrate provides an effective means of regional anticoagulation during continuous renal replacement therapy (CRRT). We evaluated the efficacy, safety and cost of a regional citrate anticoagulation protocol using commercial solutions in 17 critically ill patients treated with continuous venovenous haemodiafiltration (CVVHDF). We performed a total of 22 sessions. METHODS We delivered an A.C.D-A(541(R)) solution containing 112.9 mmol/l disodium citrate (3.22%) at a median rate of 260 (190-280) ml/h via the pre-filter port of a COBE PRISMA with an AN-69 dialyser, while adjusting the rate to maintain post-filtered ionized calcium (iCa(2+)) between 0.25 and 0.4 mmol/l. Plasma iCa(2+) was maintained at >1.1 mmol/l by infusion of calcium chloride at a median rate of 1.70 (1.36-2.27) mmol/h. The dialysate was easily modified according to the acid-base status of each patient. Both replacement and dialysate solutions were delivered at 1200 ml/h. Each session was scheduled for 48 h and biological parameters were assessed every 6 h. RESULTS The mean dialyser survival was 39 +/- 11 h (median 41.5 h; range 13-48 h). We observed dialyser clotting in four cases (18%). There were no bleeding events or modifications of coagulation parameters. The citrate solution, replacement solution and dialysate were obtained as commercial products. Both the replacement and dialysate solutions contained calcium. The extra cost of this technique was 25 euro;/day as compared to anticoagulation with heparin. CONCLUSIONS We designed an efficient method of regional citrate anticoagulation for CVVHDF by using commercial solutions. The monitoring of patients was as intensive as during heparin anticoagulation for CRRT. Because of the higher cost of this method, it should be proposed only for patients with high bleeding risk.

Background: Long-term renal transplant (RT) recipient mortality and graft loss increase significantly in hepatitis C virus positive (HCV-[+]ve) patients. Treatment with α-interferon in this population is associated with a high rate of acute rejection. The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+) RT patients (group A) matched to 32 HCV-(+) RT patients (group B) who did not receive ribavirin. Methods: Ribavirin was started at a daily dose of 1,000 mg and then adapted to hemoglobin level. The study was scheduled for 1 year. Results: Ribavirin monotherapy was associated with a decrease in liver enzymes and serum creatinine levels. When proteinuria was present, this decreased or disappeared. There were no significant changes in HCV viremia. There was a significant progression in liver fibrosis with no improvement in inflammation scores. Hemoglobin levels fall dramatically, despite an important support by recombinant erythropoeitin (median, 20,000 IU/wk). In 3 cases, ribavirin therapy had to be stopped. In the control group, after 1 year of follow-up, there was a significant increase in serum alanine aminotransferase and creatinine values. Proteinuria decreased in only 2 of 12 patients ( P = 0.03 as compared with group A). Conclusion: One year of ribavirin monotherapy seems to have, at best, no beneficial effect on liver histology, although it improves liver enzyme levels. Despite its efficiency to dramatically decrease proteinuria, its impact on renal function remains unknown.

Leucopenia and diarrhoea are the main side effects observed after the use of mycophenolate mofetil (MMF) in renal-transplant patients. The mechanism of diarrhoea remains unknown. We report on four cases presenting with severe diarrhoea, which appeared, respectively, at 4, 10, 24, and 66 months after MMF therapy had been started. All patients presented with weight loss and biological signs of malabsorption syndrome. Oesophago-gastroduodenoscopy revealed duodenal villous atrophy, which was confirmed by pathology examination. Anti-endomysium antibodies were negative. In all patients, diarrhoea disappeared within 1 month of MMF withdrawal without a gluten-free diet. A control oesophago-gastroduodenoscopy was performed in one patient 6 months later and was considered normal. None of the patients showed evidence of cytomegalovirus in enterocytes or cytomegalovirus-positive viraemia. In conclusion, villous atrophy induced by MMF might be one of the mechanisms of diarrhoea. It is mandatory to differentiate coeliac disease from MMF-induced villous atrophy because, in the latter case, a gluten-free diet is not required.

Introduction Certaine etudes suggerent que lors d’une encephalopathie hepatique, une hypertension intracrânienne (HTIC) peut dans certains cas etre observee [1] . Toutefois, l’incidence de l’HTIC lors d’une encephalopathie hepatique reste inconnue. Evaluation de l’incidence de l’hypertension intracrânienne (HTIC) par methodes non invasives chez les patients presentant une encephalopathie hepatique et son evolution avec le traitement de la maladie hepatique. Materiel et methodes Etude prospective, observationnelle au sein d’un CHU. Des patients presentant une encephalopathie hepatique (criteres de West Haven) ont ete inclus. Les patients ont beneficie d’une estimation non invasive de la pression intracrânienne par mesure echographique du diametre des enveloppes du nerf optique (DENO) (HTIC si > 0,58 cm) et mesures des velocites cerebrales dans les arteres cerebrales moyennes (ACM) au Doppler transcrânien (DTC) de l’inclusion et jusqu’a 4 jours apres le debut de l’etude (j4). Les tests de Mann-Whithney ou Kruskal-Wallis ont ete appliques quand ils etaient appropries ( p significatif Resultats Vingt-neuf patients ont ete inclus. Le DENO median a j0 etait de 0,54 cm (extremes de 0,42 a 0,60 cm). Il n’y avait pas de differences ou pour les velocites au DTC entre les differents stades d’encephalopathie pour les DENO a j0 ( p = 0,13) et a j1 ( p = 0,41), ni pour les index de pulsatilite ( p = 0,38 pour les IP droits et p = 0,39 pour les IP gauches), entre les differents groupes d’encephalopathie clinique a j0 et a j1 ( Fig. 1 ). De meme, l’analyse de l’evolution lors du traitement de l’encephalopathie ne retrouvait pas de differences significatives entre les valeurs des DENO ( p = 0,7) et les index de pulsatilite (IP) des ACM entre j0 et j4 (IP droit p = 0,4 et IP gauche p = 0,5). Discussion La mesure par des techniques non invasives ne confirment pas la presence d’HTIC chez les patients en encephalopathie hepatique.

Introduction: Cystatin C could be a relevant residual glomerular filtration rate marker during hemodialysis (HD), and a high cytokine plasma (p) rate is associated with an increase in mortality during sepsis. To the best of our knowledge, cytokines and cystatin C kinetics during and after HD during sepsis have never been studied. In this study, we described p cytokines and cystatin C variations during and after hemodialysis in septic-shock patients with acute kidney injury (AKI). Methods: Ten patients, from two tertiary ICUs, with septic shock-related AKI, according to RIFLE class F, were studied. In this prospective observational study, blood samples were collected at the start, after 1 hour, 2 hours, and at the end of HD with a polymethymethacrylate (PMMA) hemodialyzer (D0, D1, D2, and endD), and 30, 60, 90, 120, and 180 min after HD (postD0.5, postD1, postD1.5, postD2, and postD3). We measured p interleukins (IL)-6, IL-8, IL-10, cystatin C, and albumin. Results are expressed as variations from D0 (mean ± SD). Results: During HD, p[IL-6] did not vary significantly, whereas p[IL-8] and p[IL-10] reductions by D1 were 31.8 ± 21.2% and 36.3 ± 26%, respectively (P < 0.05 as compared with D0). At postD3, p[IL-8] and p[IL-10] returned to their initial values. p[Cystatin C] was significantly reduced from D1 to postD1, with a maximal reduction of 30 ± 6.7% on D2 (P < 0.05). Norepinephrine infusion rate decreased from D0 to postD3 (0.65 ± 0.39 to 0.49 ± 0.37 μg/kg/min; P < 0.05). Conclusions: HD allows a transient and selective decrease in p cytokines, which are known as being correlated with mortality during septic shock. Because of a significant decrease in p cystatin C during HD, this should not be considered as an accurate marker for residual glomerular filtration rate during septic acute renal failure when receiving HD with a PMMA hemodialyzer.