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Background There is an unmet need to develop safe and successful heparin-free regional anticoagulation modalities in haemodialysed patients at risk of bleeding. Whether the addition of citrate as a prefilter injection or in the dialysate itself is required to reach anticoagulation objectives when calcium-free dialysate is used as regional anticoagulation remains unclear. Methods In this monocentric retrospective study, we report our experience of 908 dialysis sessions performed with a calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance, without additional heparin. Results Premature termination for filter clotting occurred in 20 sessions (2.2%) and duration of session was >4.5 h in 135 (15%; maximum duration 6 h). In addition, we could investigate the citrate, calcium and acid–basis status during haemodialysis sessions performed with (citrate group, n = 20 sessions) or without (citrate-free group, n = 19 sessions) citrate in the dialysate. In 20 sessions performed in patients with underlying liver disorders and using calcium-free citrate-containing dialysate, patients’ ionized calcium (iCa) and serum citrate levels were stable and remained within the normal range, respectively. Post-filter iCa was below 0.4 mmol/L in 19/20 sessions and citrate was 0.304 mmol/L (range: 0.011; 0.548). In 19 sessions that used calcium and citrate-free dialysate, post-filter iCa was 0.41 mmol/L (0.34; 0.5) and all sessions extended to 4 h or beyond. Conclusions Regional anticoagulation of haemodialysis with a calcium-free dialysate and calcium reinjection according to the ionic dialysance is safe. Adding citrate to the dialysate is not mandatory to prevent dialysis circuit clotting in most patients.

Rationale There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. Design Observational prospective study. Setting Two ICUs in a teaching hospital (France). Patients Eighty patients with sepsis admitted to the ICU. Interventions Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). Measurements and main results Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. Conclusions Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.

International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2

The immunogenicity of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccine was improved by the administration of a third dose. The aim of our retrospective study was to assess the evolution of binding and neutralizing antibody concentration until 3 months after the third dose in a large cohort of solid organ transplant (SOT) patients (n = 872). At 1 month after the third dose, anti-SARS-CoV-2 antibodies were detected by means of enzyme-linked immunosorbent assay tests in 578 patients (66.3%). In a subgroup of patients, 70% (180 out of 257) had anti-SARS-CoV-2 antibody concentrations ranging from 1.2 to 18 411 binding antibody units (BAU)/ml and 48.5% (115 out of 239) had a neutralizing antibodies titer that can confer clinical protection against SARS-CoV-2. Three-hundred ninety-three patients out of the 416 (94.5%) who were seropositive at month 1 and were tested at 3 months after vaccination remained seropositive. Between months 1 and 3 after vaccination, binding and neutralizing antibodies concentrations decreased significantly. The proportion of protected patients against the SARS-CoV-2 also slightly decreased. In conclusion, this study shows that although two-third of SOT develop anti-SARS-CoV-2 antibodies after three doses, one-third of them remain weak or non-protected. It is important to measure anti-SARS-CoV-2 antibodies to define the strategy that can optimize SOT protection against SARS-CoV-2.

International audience; Intradialytic hypotension (IDH) is one of the most frequent and worrying issues in chronic hemodialysis. Systolic blood pressure (BP)

BACKGROUND Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients. OBJECTIVES To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients. PATIENTS/METHODS Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA. RESULTS Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis. CONCLUSIONS Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.

Objectives Antibody-mediated rejection is a main cause of long-term kidney allograft loss. Nonad-herence and tacrolimus intrapatient variability have been identified as risk factors for developing de novo donor-specific antibodies. Tacrolimus, given once daily, can improve adherence and reduce variabilities among patients. The aim of this retrospective observational study was to compare the incidences of donor-specific antibodies at 2 years posttransplant in de novo kidney transplant recipients given tacrolimus either once or twice daily. Materials and methods Non-HLA sensitized de novo kidney-transplant recipients given tacrolimus either once daily (n = 82) or twice daily (n = 168), combined with mycophenolic acid with or without steroids, were included in the study. All patients were screened for anti-HLA antibodies before transplant, at 6, 12, and 24 months posttransplant, and each time the patient presented with impaired kidney function. Results The 2-year incidence of donor-specific antibodies was 2.8%. During the follow-up period, 6 patients (3.6%) receiving tacrolimus twice daily and one patient (1.2%) receiving tacrolimus once daily developed a donor-specific antibody (P = .43). The incidence of antibody-mediated rejection was 4.8% under tacrolimus once daily and 2.7% under tacrolimus twice daily (P = .5). Tacrolimus intrapatient variability was similar with both formulations and was not associated with development of donor-specific antibodies. Conclusions The use of tacrolimus-based immunosup-pression associated with mycophenolic acid was associated with a low risk of de novo donor-specific antibodies. After 2 years, the incidence of de novo donor-specific antibodies did not differ significantly between patients treated with tacrolimus once daily versus those treated with the twice-daily formulation.

Background: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency. Objectives: To describe the various presentations and identify predictive factors of death in patients with CPX. Methods: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days). Results: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes. Conclusions: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.

Thrombotic microangiopathy (TMA) brings together many diseases that have a commonality in the apparition of mechanical hemolysis with consuming thrombopenia. In all cases, these diseases can be life threatening, thereby justifying the implementation of treatment as an emergency. First-line treatment represents plasma exchange. This treatment has proven efficiency in improving the vital patient's and functional prognosis. However, the administration methods of plasma exchange can be redefined in light of the understanding of the pathophysiology of TMA. The aim of this review is to try to define, from pathophysiology, the place of plasma exchanges in the modern therapeutic arsenal of TMA.

International audience; Objectives: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients.Methods: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors.Results: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load

Intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately worsens long-term kidney outcomes in critically ill patients requiring kidney replacement therapy. Acetate-free biofiltration (AFB), an alternative technique to bicarbonate-based hemodialysis (B-IHD) that does not require dialysate acidification, may improve hemodynamic and metabolic tolerance of dialysis. In this study, we included 49 mechanically ventilated patients requiring 4 h dialysis (AFB sessions n = 66; B-IHD sessions n = 62). Whereas more AFB sessions were performed in patients at risk of hemodynamic intolerance, episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used (decrease in mean blood pressure ≥ 10 mmHg; systolic blood pressure decrease >20 mmHg or absolute value below 95 mmHg) and after adjustment on the use of vasoactive agent. Diastolic blood pressure readily increased throughout the dialysis session. The use of a bicarbonate zero dialysate allowed the removal of 113 ± 25 mL/min of CO2 by the hemofilter. After bicarbonate reinjection, the global CO2 load induced by AFB was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD (p = 0.0002). Thus, notwithstanding the non-controlled design of this study, hemodynamic tolerance of AFB appears superior to B-IHD in mechanically ventilated patients. Its use as a platform for CO2 removal also warrants further research.

Introduction Les hypotensions intra-dialytiques (HID) sont un probleme majeur en dialyse malgre l’amelioration continue des pratiques (membranes biocompatibles, profils d’ultrafiltration, hemodiafiltration), et sont un facteur predictif de morbi-mortalite cardiovasculaire. L’acidification du dialysat pour eviter la carbonatation des filtres en presence de bicarbonate et de calcium s’accompagne d’une charge en CO2 massive pouvant favoriser les HID. Le recours a un dialysat sans bicarbonate et donc sans acide (avec reinjection post-filtre de bicarbonate ; AFB) pourrait ameliorer la tolerance hemodynamique des seances de dialyse. Description Etude monocentrique retrospective (avril 2019–janvier 2021). Methodes Recueil des parametres cliniques et biologiques lors des seances de dialyses sur une periode de 6 mois (M − 3 a M0 : dialyses conventionnelles ; M0 a M3 : AFB) soit plus de 1600 seances. Resultats Vingt-trois patients ont ete inclus (duree mediane en dialyse de 4 ans [0,5–22], âge median 68 ans [35–92]), dont 52 % etaient diabetiques et 40 % avaient une cardiopathie connue. Quelle que soit la definition de l’HID utilisee (KDIGO, ERBP, UK), le nombre d’evenements etait significativement diminue apres passage en AFB, sans variation concomitante significative du poids sec. L’amelioration de l’hemodynamique etait principalement associee a une augmentation des pressions diastoliques pre- et post-seances (p Conclusion La biofiltration reduit significativement l’incidence des hypotensions intra-dialytiques, s’accompagne d’une majoration de la pression arterielle diastolique pre- et per-dialyse et ameliore la tolerance globale des seances d’HDI.

Objectives Critically ill patients who have a high risk of bleeding but require prolonged intermittent dialysis need a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit. We assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance. Design Prospective cohort study. Setting Critical care units. Patients Critically ill patients who required renal replacement therapy. Interventions None. Measurements and main results A total of 101 dialysis sessions were performed in 35 patients (mechanical ventilation n = 78; norepinephrine n = 13). Median duration of dialysis was 294 minutes (interquartile range, 240-300), and median ultrafiltration volume was 2.3 L (1-2.8). Urea and β2-microglobulin reduction rates were 64.5% ± 0.4% and 48% ± 0.13%, respectively. Postfilter ionized calcium was 0.35 ± 0.17 and 0.38 ± 0.14 mmol/L at 1 and 3 hours, respectively, within the extracorporeal circuit. A major clotting event that led to premature termination of the session occurred in only three of 101 sessions. In these three cases, major catheter dysfunction occurred before clotting within the circuit. Prefilter ionized calcium remained within narrow ranges (before/after change +0.07 ± 0.006 mmol/L), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged. Conclusions Dialysis anticoagulation with calcium-free citrate-containing dialysate and calcium reinjection according to ionic dialysance is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. It allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. Furthermore, sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe acute kidney disease.

Background Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors. Methods Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7–68]; time from transplantation 41 months [IQR 5–119]). Survival curves were compared using the Log-rank test. Results Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function. Conclusions Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.

There is no recommendation regarding the type of induction therapy to use in ABO-incompatible (ABOi) kidney transplantation. The aim of this retrospective study was to compare the outcome of ABOi living donor kidney transplant (LDKT) recipients who received either polyclonal antibodies or anti-interleukin-2 receptor (IL-2R) blockers as an induction agent. All ABOi HLA-compatible patients that received a LDKT between 03/11 and 03/18 in three French transplantation center (Paris Saint-Louis, Paris Necker, and Toulouse) were included in the study. Fifty-eight patients were given polyclonal antibodies and 39 patients received anti-IL-2R blockers. We identified by a Cox proportional hazard model the use of polyclonal antibodies as a protective factor against acute rejection (HR = 0.4, 95%CI [0-0.9], P

International audience; Hepatitis E virus genotype 3 (HEV3) and 4 (HEV4) can progress to chronic hepatitis in immunosuppressed patients.1 Ribavirin therapy has been shown to be efficient for treating chronic HEV infection in solid-organ-transplant recipients.2,3 Eighty percent of patients achieved a sustained virological response 24 weeks (SVR24) after ribavirin cessation.3 However, the optimal duration of ribavirin therapy is still undetermined. A rapid decrease of HEV RNA in blood under therapy was associated with SVR24.4 It has also been suggested that the presence of HEV polymerase mutations, such as the 1634R mutant, could influence the response to ribavirin therapy.5,6 We previouslyshowed that persistence of HEV RNA in the feces at the end of ribavirin therapy in patients with undetectable HEV RNA in blood was also associated with a higher risk of HEV infection relapse.7 This prompted us to prolong the duration of ribavirin therapy in patients who had undetectable HEV RNA in the serum but persistent detectable HEV RNA in the stools at the end of the scheduled duration. Herein, we retrospectively compared the SVR24 in solid-organ-transplant recipients for whom ribavirin treatment was prolonged when HEV RNA was still detectable only in the stools, to the SVR24 in a historical group of patients in whom ribavirin was systematically stopped at theend of the scheduled duration.

Background Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40-50%), and liver tests abnormalities (40-70%). In HNF1B patients who reach end-stage renal disease, single kidney transplantation (SKT) or combined kidney-pancreas transplantation can be considered. Methods A retrospective multicenter study including 18 HNF1B patients receiving SKT or kidney-pancreas transplantation, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure. Results After SKT, 50% of the HNF1B patients develop early posttransplantation diabetes mellitus, whereas 40% experience new-onset or severe worsening of preexisting abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independent of NFATc. Conclusions Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.

Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.

Introduction Le virus de l’hepatite E (VHE) est responsable d’hepatites aigue et chronique chez les patients transplantes d’organe solide. Bien que le foie soit considere comme le principal site de replication virale, l’ARN du VHE ainsi que l’antigene de capside (Ag) ont ete detectes dans le tractus digestif ou les reins dans des modeles animaux, laissant supposer l’existence de sites de replication extra-hepatiques. Methodes Nous avons etudie l’excretion urinaire du VHE de genotype 3 chez des patients transplantes d’organe solide a la phase aigue de l’infection. Nous avons egalement evalue la valeur pronostique des marqueurs viraux (ARN/Ag) dans le sang et l’urine. Nous avons analyse les urines de 24 patients transplantes au diagnostic de l’infection a VHE, en recherchant l’ARN viral par qRT-PCR et l’antigene de capside par technique ELISA (Wantai test). Les particules virales isolees ont ete par la suite caracterisees par ultracentrifugation. Resultats obtenus ou attendus Le genome du VHE a ete detecte dans les urines chez 50 % des patients transplantes au diagnostic de l’infection a VHE (N = 12/24). L’antigene de capside a ete detecte dans les urines chez 96 % des patients (N = 23/24). Les particules virales excretees dans l’urine etaient associees a une membrane lipidique, comme suggere par leur faible densite (1,11–1,12 g/cm3). Les virions presents dans l’urine etaient aussi infectieux in vitro que les virions du sang circulant. La detection du VHE dans les urines n’etait associee ni a une alteration de la fonction renale ni a une proteinurie de novo. Enfin, les patients evoluant vers la chronicite presentaient, a la phase aigue de l’infection, un taux plus eleve d’antigene viral dans le serum que ceux ayant une infection resolutive. Conclusion Le VHE est frequemment excrete dans les urines de patients transplantes d’organe solide sans repercussion apparente sur la fonction renale. L’antigenemie virale au diagnostic pourrait etre un marqueur predictif d’evolution vers la chronicite.

International audience; Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

We read with interest the case report by Dhondup et al., who suggest that combined liver–kidney transplantation should be considered for patients with end-stage chronic kidney disease (CKD) caused by primary hyperoxaluria type 2 (PH2). This is in contrast to isolated kidney transplantation that is usually proposed (1). This article is protected by copyright. All rights reserved.

This is the case of a 56-year-old man who underwent heart transplantation. Within the first postoperative days, his respiratory and limb muscles weakened, which was attributed to critical illness polyneuromyopathy (CIPM). At day 70 post transplantation, he had increased liver enzyme levels and acute hepatitis E virus (HEV) infection was diagnosed. HEV RNA was found in the serum, stools, and cerebrospinal fluid. Results of further investigations suggested a possible HEV-related polyradiculoneuropathy. At transplantation, the patient was negative for immunoglobulin (Ig)G, IgM, and HEV RNA. A trace-back procedure identified the source of infection and concluded that HEV infection was contracted from blood transfusion 12 days prior to transplantation from an HEV RNA-positive donor. Tests of the organ donor for HEV were negative. Phylogenetic analysis revealed sequence homology between the HEV-3 strain of the patient and the HEV-3 strain of the blood donor. Despite ribavirin treatment, the patient died on day 153 post transplantation from multiorgan failure. In conclusion, patients with hepatitis or neuropathic illness that have received blood products should be screened for HEV. This article is protected by copyright. All rights reserved.

BACKGROUND: Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization. METHODS: We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay. RESULTS: Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (

Introduction L’utilisation d’un dialysat sans calcium (dsCa) permet une anticoagulation efficace des circuits de dialyse, sans anticoagulation systemique, moyennant la reinjection de calcium adapte a la dialysance ionique. Les dsCa contiennent habituellement du citrate mais l’interet (concentration faible 0,3 mM : soit largement inferieure a la concentration minimale de 3 mM necessaire pour anticoaguler efficacement les circuits de dialyse) et la tolerance de celui-ci (risque d’accumulation au cours des seances longues, en particulier en cas d’hepatopathie) sont incertains. Methodes Etude retrospective evaluant l’equilibre acido-basique, et les taux de citrate/calcium au cours des seances d’HDI-dsCa chez des malades de reanimation presentant une hepatopathie. Resultats obtenus ou attendus Vingt seances d’HDI-dsCa (5 heures n = 18 ; arret premature n = 2) realisees chez 18 patients (TP median 69 % (35 ; 100), cytolyse 2,5 N (1 ; 100), score de Child > A6 n = 14) ont ete analysees. La citratemie est restee dans les normes ( Conclusion L’HDI-dsCa repose principalement sur la perte de calcium au travers du filtre et non sur l’apport de citrate par le dialysat, permettant d’envisager l’utilisation de dialysat sans citrate. Aucune intoxication au citrate n’a ete identifiee malgre des seances longues et une hepatopathie sous-jacente chez la majorite des patients.

Introduction Les infections a champignons filamenteux (ICF : aspergillose invasive, mucormycose, alternariose…) sont rares mais graves apres transplantation d’organe solide (TOS). Leurs presentations cliniques et leur devenir sont largement meconnus. Methodes Dans cette etude retrospective monocentrique, tous les TOS ayant developpe une ICF entre janvier 2008 et decembre 2016 ont ete inclus. Les facteurs associes a la mortalite a 1 an en analyse univariee ont ete identifies puis les facteurs predictifs independants en analyse multivariee (regression logistique) ont ete retenus. Resultats obtenus ou attendus Parmi les 1739 patients ayant une greffe d’organe solide au cours de cette periode, 68 ont developpe une ICF, dont 58 une aspergillose invasive (AI). L’incidence cumulee d’ICF a 1 an etait de 18,8, 11,1, 1,7 et 1,2 % chez les receveurs de greffe cardiaque, pulmonaire, hepatique et renale, respectivement. Le diagnostic d’ICF a ete pose par la culture (96 %) ou l’examen direct (73 %) d’un echantillon biologique, ou une augmentation du galactomannan serique (35 %). Au diagnostic, en comparaison avec les autres ICF, un etat de choc etait plus frequent et un diabete moins frequent chez les patients avec une AI. Au cours du suivi, 35 patients (51 %) ont ete admis en reanimation, et ont requis une ventilation mecanique (n = 27), des amines vasopressives (n = 31) ou une epuration extra-renale (n = 31). Chez les patients avec AI, les deux seuls parametres independamment associes avec le risque de deces a 1 an (n = 33 ; 57 %) etaient le besoin en support vasopresseur (OR 7,34 ; 95 %CI 1,95–27,6 ; p = 0,003) et un examen direct positif (OR 10,1 ; 95 %CI 2,05–49,8 ; p = 0,004). Conclusion Les caracteristiques des ICF au diagnostic varient selon l’organe greffe et le type d’infection. Chez les TOS developpant une aspergillose invasive, la mortalite a un an est elevee malgre une prise en charge aggressive et peut etre predite par le besoin en support vasopresseur et la charge fongique initiale.

OBJECTIVES Scarce data exist regarding the effect of acute graft pyelonephritis on kidney histology after a kidney transplant. This study sought to assess the kidney histology at 1 month, and kidney function at 1 year, after acute graft pyelonephritis in kidney transplant patients. MATERIALS AND METHODS All kidney transplant patients with acute graft pyelonephritis between October 2006, and December 2008, underwent a kidney biopsy 1 month later (n=28). Histologic findings were compared with those observed in a control group (n=28) who underwent a protocol kidney biopsy at 1 year posttransplant and did not present with acute graft pyelonephritis. Patients were matched according to age, sex, and immunosuppressive regimen. RESULTS Kidney function was impaired by the acute graft pyelonephritis episodes at the time of biopsy. In 40% of patients, the estimated glomerular filtration rate did not return to baseline by 1 month after acute graft pyelonephritis and remained impaired thereafter. Three patients had features of acute rejection. Tubulitis was seen more frequently in the acute graft pyelonephritis group, especially in patients in whom estimated glomerular filtration rate did not completely recover by 1 month after acute graft pyelonephritis. Patients with acute graft pyelonephritis who had inflammatory infiltrate of > 20% 1 month after acute graft pyelonephritis had worse kidney function 1 year later. CONCLUSIONS After transplant, when kidney function remains impaired 1 month after acute graft pyelonephritis, kidney biopsies allowed graft rejection diagnosis and predicted kidney function recovery.

Background and Aim Liver transplantation remains the best option for treating type-1 hepatorenal syndrome (HRS1). The aim of this retrospective study was to determine whether the molecular adsorbent recirculation system (MARS) can improve renal function in HRS1 patients. Methods Thirty-two patients with chronic liver disease and HRS1 were treated by MARS sessions which were performed every other day. The endpoint was renal function improvement by 28 days after diagnosis of HRS1 that was defined as a serum-creatinine level of

Background Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and HCV infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication. Patients and methods A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months. Results During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs. 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and four from the HCV-negative group developed a lymphoma. Only two patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group. Conclusion The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients. This article is protected by copyright. All rights reserved.

Background Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Methods Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. Results DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07–6.49); p

International audience; There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new‐generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon‐free sofosbuvir‐based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty‐five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated‐interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti‐HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New‐generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation.

BACKGROUND Dosing of enteric-coated mycophenolate sodium (EC-MPS) should be adjusted to reflect concomitant immunosuppression, but it is largely undocumented whether such modifications are carried out during routine clinical practice. MATERIAL AND METHODS MyLIFE was an observational study of adult kidney-only or kidney-pancreas transplant patients starting -EC-MPS at 33 French transplant centers. Data were collected at first EC-MPS dose and 6 months later. The primary objective was to describe initial EC-MPS dosing according to concomitant immunosuppression. RESULTS There were 461 patients analyzed (174 started EC-MPS by month 1 post-transplant ['de novo'] and 287 started EC-MPS >1 month post-transplant ['maintenance']), receiving cyclosporine (CsA) (n=76), tacrolimus (n=363), or a mammalian target of rapamycin (mTOR) inhibitor (n=22). Mean (SD) starting dose was 1130 (511) mg/day, 1006 (441) mg/day, and 769 (300) mg/day in the CsA, tacrolimus, and mTOR inhibitor groups, respectively (p=0.003). In the de novo subpopulation, the starting dose was 1440 mg/day in 66.7% (14/21) of CsA-treated patients and 71.9% (110/153) of tacrolimus-treated patients, with an intensified dose of 2160 mg/day in 28.6% (6/21) and 8.5% (13/153), respectively. There was a non-significant trend to a higher rate of biopsy-proven acute rejection in patients receiving CsA versus tacrolimus or an mTOR inhibitor (p=0.082). Adverse events with a suspected relation to EC-MPS occurred in 21.0%, 23.1%, and 9.1% of the CsA, tacrolimus, and mTOR inhibitor subpopulations, respectively. CONCLUSIONS EC-MPS is usually initiated at the dose recommended for de novo CsA-treated kidney transplant patients, then titrated downwards as required. An early intensified regimen is not used frequently. The EC-MPS dose is modified in

The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in small-sized cohorts or by aggregating patients receiving a variety of therapies that include aggressive (i.e., combined plasma exchanges, corticosteroids, and cyclophosphamide) and less aggressive (i.e., either plasma exchanges or immunosuppressive drugs, or no treatment). To address the prognosis of GS patients with relatively homogeneous management including plasma exchanges, we conducted a multicenter retrospective study on GS patients included in the registry of the French Society of Hemapheresis. 122 patients were included (kidney alone (n = 28), lung alone (n = 5), or combined involvement (n = 89)). All 122 patients received plasma exchanges (median number of sessions: 13 [9-17]), either alone (n = 8) or associated with combined corticosteroids and oral or IV cyclophosphamide (n = 101) or with corticosteroids alone (n = 12) or cyclophosphamide alone (n = 2). One-year survival was 86.9%. 7/16 patients died from severe infection. In multivariate analyses (Cox's regression model), being aged60 years, and number of plasma exchanges were correlated to overall survival. The use of alternative immunosuppressive drugs (because of refractory or relapsing GS) was correlated to mortality at one year. Superiority of oral cyclophosphamide compared to intravenous intake was close to significant. Using a logistic regression model, renal survival in patients alive at 1 year was only predicted by serum creatinine500 μmol/L at presentation. This large series describes the predictive factors for overall and renal survival of GS patients treated by plasma exchanges. Interventional studies that compare oral and intravenous cyclophosphamide, as well as testing new immunosuppressive therapies, are warranted.

Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place.After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 538 ± 347 days.At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P0.001); anti-human leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy.The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.

Introduction En reanimation, les patients sont a la fois a risque de saignements systemiques et de thromboses des circuits de dialyse. L’objectif de cette etude etait de demontrer l’efficacite et la securite d’une anticoagulation regionale (ARC) des circuits, sans heparine, a l’aide d’un dialysat au citrate sans calcium avec une reinjection de calcium selon la dialysance ionique (DI), et cela chez des patients de reanimation beneficiant de seances longues. Patients et methodes Etude prospective observationnelle monocentrique (reanimation medicale). Inclusion de tous les patients ayant beneficie d’une HDI avec une ARC sans heparine (amorcage au serum sale, Qsang 300 mL/min ; Qdial 500 mL/min ; dialysat : citrate 0,8 mM, calcium 0, magnesium 0,5 M). La reinjection de calcium (300 mM) en sortie de dialyse etait adaptee a la DI mesuree toutes les 30 minutes (Reinj [mL/min] = DI/200). Resultats Entre avril 2016 et janvier 2017, 35 patients ont beneficie de 101 seances d’HDI par ce protocole d’ACR (ventilation mecanique 78 % ; norepinephrine 13 %). La duree mediane de la seance a ete de pres de 290 minutes (75 % > 4 heures, max. 6 heures) avec un volume d’ultrafiltration de 2,3 litres (IQR : 1–2,8). Au total, 3/101 seances ont necessite une interruption prematuree par coagulation du circuit, a chaque fois secondaire a une dysfonction majeure du catheter de dialyse temporaire. La tolerance hemodynamique a ete excellente. Le calcium ionise (iCa) post-filtre etait toujours dans les objectifs (0,35 ± 0,17 et 0,38 ± 0,14 mmol/L a H1 et H3). L’iCa pre-filtre (systemique) etait stable (1,15 ± 0,006 mmol/L). L’efficacite de l’epuration a ete excellente (taux de reduction de l’uree et de la s2-microglobuline de 64,5 ± 4 % et 48 ± 13 %, respectivement). Discussion L’excellente efficacite de l’anticoagulation, en l’absence de toute injection d’heparine, et l’absence de necessite de surveiller l’iCa systemique permettent de moduler en continu la duree de la seance et donc l’UF horaire en fonction de la tolerance hemodynamique du patient. L’effet immunomodulateur du citrate (biocompatibilite) pourrait ameliorer la tolerance des seances d’HDI en reanimation. Conclusion L’anticoagulation des seances d’HDI avec un bain au citrate sans calcium et une reinjection de calcium asservie a la DI est efficace, sure, peu chere et ne necessite pas de dosages d’iCa systemique iteratifs.

Summary Background and objectives Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. Design, setting, participants, & measurements We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis–associated AON followed in four French renal units. Results Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n 6]; oral antidiabetic drugs [n 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. Conclusion AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented. Clin J Am Soc Nephrol 6: 1895–1902, 2011. doi: 10.2215/CJN.00010111

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%; P < 0.001) 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.

It has been shown that hepatitis E virus (HEV) may be responsible for chronic hepatitis in solid-organ transplant patients. It has also been suggested that HEV may be responsible for atypical neurological symptoms during the acute phase. However, the relationship between the neurological symptoms and HEV infection was based on the detection of anti-HEV IgM in the sera. Herein, we report a case where neurological symptoms, that is peripheral nerve involvement with proximal muscular weakness that affected the four limbs joints with central nervous-system involvement and bilateral pyramidal syndrome, occurred in a kidney-transplant patient who was chronically infected by HEV. For the first time, HEV RNA was detected in the serum and cerebrospinal fluid. In addition, clonal HEV sequences were analyzed in both compartments, that is serum and cerebrospinal fluid. The discovery of quasispecies compartmentalization and its temporal association suggests that neurological symptoms could be linked to the emergence of neurotropic variants.