Publications by authors named "Valérie Moal"

86 Publications

Peri-operative risk factors of chronic kidney disease after liver transplantation.

J Nephrol 2021 Aug 23. Epub 2021 Aug 23.

Department of Digestive Surgery and Liver Transplantation, Hôpital la Timone, 264 Rue Saint-Pierre, 13385, Marseille Cedex 05, France.

Background: Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases.

Methods: All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline.

Results: Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h ≥ 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019.

Conclusions: The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-021-01127-6DOI Listing
August 2021

Isolation of Viable SARS-CoV-2 Virus from Feces of an Immunocompromised Patient Suggesting a Possible Fecal Mode of Transmission.

J Clin Med 2021 Jun 18;10(12). Epub 2021 Jun 18.

Institut de Recherche pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille, Microbes Evolution Phylogeny and Infections (MEPHI), Aix Marseille Université, 13005 Marseille, France.

(1) Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) excretion in stools is well documented by RT-PCR, but evidences that stools contain infectious particles are scarce. (2) Methods: After observing a Corona Virus 2019 Disease (COVID-19) epidemic cluster associated with a ruptured sewage pipe, we search for such a viable SARS-CoV-2 particle in stool by inoculating 106 samples from 46 patients. (3) Results: We successfully obtained two isolates from a unique patient with kidney transplantation under immunosuppressive therapy who was admitted for severe diarrhea. (4) Conclusions: This report emphasizes that SARS-CoV-2 is an enteric virus, and infectious virus particles can be isolated from the stool of immune-compromised patients like, in our case, kidney transplant recipient. Immune-compromised patients are likely to have massive multiplication of the virus in the gastrointestinal tract and this report suggests possible fecal transmission of SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10122696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235306PMC
June 2021

Polymer-free hydrogel made of lipid nanocapsules, as a local drug delivery platform.

Mater Sci Eng C Mater Biol Appl 2021 Jul 14;126:112188. Epub 2021 May 14.

Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France. Electronic address:

Nanoparticle-loaded hydrogels are attractive pharmaceutical drug delivery systems that combine the advantages of both hydrogel (local administration and/or sustained drug release) and nanoparticle (stealthiness, targeting and decreased toxicity). The design of nanoparticle-loaded hydrogels is largely conventional, consisting of the dispersion of nanoparticles in a natural or synthetic polymer matrix to form a gel network. Novel nanoparticle-loaded hydrogels architecture could provide advantages in terms of innovation and application. We focused on the development of lipid nanocapsule (LNC)-based hydrogels without the use of a polymer matrix as a platform for drug delivery. Cytidine was modified by grafting palmitoyl chains (CytC16) and the new entity was added during the LNC phase-inversion formulation process allowing spontaneous gelation. Positioned at the oil/water interface, CytC16 acts as a crosslinking agent between LNCs. Association of the LNCs in a three-dimensional network led to the formation of polymer-free hydrogels. The viscoelastic properties of the LNC-based hydrogels depended on the LNC concentration and CytC16 loading but were not affected by the LNC size distribution. The LNC and drug-release profiles were controlled by the mechanical properties of the LNC-based hydrogels (slower release profiles correlated with higher viscoelasticity). Finally, the subcutaneous administration of LNC-based hydrogels led to classic inflammatory reactions of the foreign body-reaction type due to the endogenous character of CytC16, shown by cellular viability assays. New-generation nanoparticle-loaded hydrogels (LNC-based polymer-free hydrogels) show promise as implants for pharmaceutical applications. Once LNC release is completed, no gel matrix remains at the injection site, minimizing the additional toxicity due to the persistence of polymeric implants. Sustained drug-release profiles can be controlled by the mechanical properties of the hydrogels and could be tailor-made, depending on the therapeutic strategy chosen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112188DOI Listing
July 2021

Living kidney donor evaluation for all candidates with normal estimated GFR for age.

Transpl Int 2021 06 20;34(6):1123-1133. Epub 2021 May 20.

Nephrology, Hemodialysis, Apheresis and Transplantation Department, University Hospital, Grenoble, France.

Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is <90 ml/min/1.73 m (KDIGO guidelines) or 80 ml/min/1.73 m (most US centres). However, age-related GFR decline results in a lower eGFR for older candidates. That may limit the number of older kidney donors. Yet, continuing the screening with a GFR measure increases the number of eligible donors. We hypothesized that in-depth screening should be proposed to all candidates with a normal eGFR for age. We compared the evolution of eGFR after donation between three groups of predonation eGFR: normal for age (S ) higher than 90 or 80 ml/min/1.73 m (S and S respectively); across three age groups (<45, 45-55, >55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S than in S or S but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13870DOI Listing
June 2021

Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study.

Transplantation 2021 08;105(8):1858-1868

Department of Pathology, INSERM U955, APHP Hôpital Henri Mondor, Université Paris-Est, Créteil, France.

Background: Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients.

Methods: All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients.

Results: T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001).

Conclusions: This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003568DOI Listing
August 2021

Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort.

Clin Kidney J 2020 Oct 21;13(5):878-888. Epub 2020 Oct 21.

Department of Nephrology and Renal Transplantation, Maison Blanche Hospital, University Hospital of Reims, Reims, France.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD).

Methods: We conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality.

Results: Among the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses.

Conclusions: COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfaa199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743188PMC
October 2020

Is COVID-19 infection more severe in kidney transplant recipients?

Am J Transplant 2021 03 28;21(3):1295-1303. Epub 2021 Jan 28.

Department of Nephrology and Transplantation, Hôpital Universitaire Necker, APHP Center, Université de Paris INEM INSERM U 1151, CNRS UMR 8253, Paris, France.

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753418PMC
March 2021

Deciphering the Urinary Microbiota Repertoire by Culturomics Reveals Mostly Anaerobic Bacteria From the Gut.

Front Microbiol 2020 16;11:513305. Epub 2020 Oct 16.

IRD, AP-HM, Microbes, Evolution, Phylogeny and Infection (MEPHI), IHU Méditerranée Infection, Aix-Marseille University, Marseille, France.

Human urine was considered sterile for a long time. However, 416 species have been previously cultured, including only 40 anaerobic species. Here, we used culturomics, particularly those targeting anaerobes, to better understand the urinary microbiota. By testing 435 urine samples, we isolated 450 different bacterial species, including 256 never described in urine of which 18 were new species. Among the bacterial species identified, 161 were anaerobes (35%). This study increased the known urine repertoire by 39%. Among the 672 bacterial species isolated now at least once from urine microbiota, 431 (64.1%) were previously isolated from gut microbiota, while only 213 (31.7%) were previously isolated from vagina. These results suggest that many members of the microbiota in the urinary tract are in fact derived from the gut, and a paradigm shift is thus needed in our understanding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.513305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596177PMC
October 2020

Tacrolimus Exposure in Obese Patients: and A Case-Control Study in Kidney Transplantation.

Ther Drug Monit 2021 04;43(2):229-237

Centre de Néphrologie et Transplantation Rénale, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception.

Background: Tacrolimus pharmacokinetics in obese (Ob) patients has been poorly studied. In this article, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population.

Methods: A retrospective, observational, monocentric case-control study was performed in obese KTRs (BMI > 30 kg/m2) who received tacrolimus between 2013 and 2017 (initial dose: 0.15 mg/kg/d) (actual weight). Nonobese (Nob) controls (BMI <30 kg/m2) were matched for age and sex. Weekly centralized monitoring of tacrolimus trough levels was performed by liquid chromatography/mass spectrometry until the third month (M3). Target trough levels were set between 8 and 10 ng/mL. All patients received antilymphocyte globulin, corticosteroids, and mycophenolate mofetil.

Results: Of the 541 KTRs, 28 tacrolimus-treated Ob patients were included and compared with 28 NOb-matched controls. With a mean of 22 assays/patient, tacrolimus trough levels were higher in Ob patients (mean 9.9 versus 8.7 ng/mL; P = 0.008); the weight-related dose of Tac was lower at M3 (mean 0.10 versus 0.13 mg/kg/d, P < 0.0001). The tacrolimus concentration to dose (C0/D) was higher in the Ob cohort [mean 116 versus 76 (ng/mL)/(mg/kg/d); P = 0.001]. In Ob patients, a mean decrease of -4.6 mg/d in the 3 months after tacrolimus initiation was required (versus -1.12 in NOb; P = 0.001) to remain within the therapeutic range. Obesity, high mycophenolate mofetil daily dose at M3, and CYP3A5 expression were independently associated with higher tacrolimus exposure. Four dose-adaptation strategies were simulated and compared with the study results.

Conclusions: An initial dose calculation based on either ideal or lean body weight may allow for faster achievement of tacrolimus trough level targets in Ob KTRs, who are at risk of overexposure when tacrolimus is initiated at 0.15 mg/kg/d. A prospective study is required to validate alternative dose calculation strategies in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000820DOI Listing
April 2021

Analytical validation of eight methods of thyroglobulin measurement in fine-needle aspiration washouts.

Ann Clin Biochem 2021 01 3;58(1):54-65. Epub 2020 Nov 3.

Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire, Angers, France.

Background: Thyroglobulin (Tg) assay in washout fluids of fine needles, after cervical lymph nodes aspiration, is used for detecting metastases from differentiated thyroid carcinomas. Assay methods are the same as for Tg in serum. However, with non-serum samples, methods require extensive validation to notably check for the absence of matrix effect. This study fits this context. Our objectives were to assess analytic performances, in washout fluid, of eight different Tg assay methods and to compare them to validated data in serum.

Methods: Eleven medical laboratories participated in this study. The matrix tested was phosphate-buffer saline containing 1% bovine serum albumin (PBS-1% BSA). Samples used were dilutions, in this buffer, of Certified Reference Material (CRM 457). We verified, for all methods, the limit of detection, precision, linearity, trueness and accuracy.

Results: In PBS-1% BSA, the functional sensitivities (FS) were comparable to those expected for serum. All the methods were linear. The relative biases of trueness were between -24.5 and 10.2% around 1 g/L. Total analytical error was ≤40% near the functional sensitivity values.

Conclusion: No quantitatively important matrix effect was observed. All the methods showed their ability to measure Tg in PBS-1% BSA, over the concentration range of interest, with acceptable total analytical error. We validated the functional sensitivity value as a decision threshold in thyroidectomized patients after treatment and with low concentrations of serum Tg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0004563220968369DOI Listing
January 2021

An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants.

Kidney Int 2020 12 24;98(6):1549-1558. Epub 2020 Aug 24.

Department of Nephrology and Transplantation, University of Lille, Lille, France.

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444636PMC
December 2020

Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity.

J Clin Med 2020 Jul 3;9(7). Epub 2020 Jul 3.

Laboratoire de Biochimie et Biologie Moléculaire, CHU Angers, 4 rue Larrey, CEDEX 9, 49933 Angers, France.

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor β gene () and exon 7 of the albumin gene (). We found 56 variants (i.e., 38% of the 303 index cases, called RTHβ group). Among the samples screened for FDH variants, 18% had the variant R218H in (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTHβ group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTHβ patients. Clinically, patients with FDH had fewer symptoms than patients with RTHβ. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9072105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408830PMC
July 2020

Renin aldosterone vasopressin and copeptin kinetics in patients with septic shock, a post-hoc Hyper2S randomized trial analysis.

Intensive Care Med 2020 04 19;46(4):808-810. Epub 2020 Feb 19.

Département de Médecine Intensive-Réanimation et Médecine Hyperbare, CHU d'Angers, France, 4 Rue Larrey, 49 993, Angers Cedex 9, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-019-05912-7DOI Listing
April 2020

Pelvic Surgery in the Transplant Recipient: Important Considerations for the Non-transplant Surgeon.

Curr Urol Rep 2020 Jan 18;21(1). Epub 2020 Jan 18.

Aix-Marseille University, Marseille, France.

Purpose Of Review: Classically, kidney transplantation (KT) consists of heterotopic implantation of the renal graft in the iliac fossa with vascular anastomosis on the iliac vessel and reimplantation of the graft ureter in the bladder of the recipient. However, a wide range of variations exist in both vascular anastomosis and urinary diversion that the non-transplant surgeon should know.

Recent Findings: For any pelvic surgery in a KT patient, the non-transplant surgeon should preoperatively evaluate the anatomy of the graft, its vascularization and its urinary tract. The transplant ureter should be identified and secured by preoperative JJ stenting whenever needed. For any surgery, maintenance and control of both immunosuppressive treatment and renal function is crucial. The advice or even the assistance of a transplant surgeon should be required because any damage to vascularization or urinary drainage of the renal graft could have dramatic and definitive consequences on graft function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11934-020-0954-9DOI Listing
January 2020

Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study.

Clin Infect Dis 2020 08;71(5):1204-1211

Department of Nephrology, CHU Rouen, Rouen, France.

Background: Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response.

Methods: Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29-1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25-18) months.

Results: After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event.

Conclusions: This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz953DOI Listing
August 2020

Temporal trends in living kidney donation in France between 2007 and 2017.

Nephrol Dial Transplant 2021 03;36(4):730-738

Agence de la Biomédecine, Saint Denis, France.

Background: Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up.

Methods: Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007-11 and 2012-17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4.

Results: We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors <56 years of age decreased significantly. The body mass index and proportion of obese donors did not change significantly. The proportion of donors with low estimated GFR for age decreased significantly from 5% to 2.2% (P < 0.001). The proportion of donors with adequate follow-up after donation increased from 19.6% to 42.5% (P < 0.001). No donor had a risk indicator equal to 4, and the proportion of donors with a risk indicator equal to 0 increased significantly from 19.2% to 24.9% (P < 0.001).

Conclusions: An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfz229DOI Listing
March 2021

Direct comparison of the specialised blood fibrosis tests FibroMeter and Enhanced Liver Fibrosis score in patients with non-alcoholic fatty liver disease from tertiary care centres.

Aliment Pharmacol Ther 2019 12 15;50(11-12):1214-1222. Epub 2019 Oct 15.

HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.

Background: The Enhanced Liver Fibrosis score (ELF) and the FibroMeter are two specialized blood fibrosis tests which include direct markers of liver fibrosis. They have been shown to be more accurate than the simple blood fibrosis tests FIB4 and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS).

Aims: To directly compare the accuracies of ELF and FibroMeter for the non-invasive diagnosis of liver fibrosis in NAFLD.

Methods: Four hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeter , NFS, and FIB4. Advanced fibrosis F3/4 on liver biopsy (NASH CRN scoring) was the primary endpoint.

Results: Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeter (0.804 ± 0.021) had significantly higher AUROC than NFS (0.722 ± 0.025, P < .010) and FIB4 (0.739 ± 0.024, P < .020). AUROC for advanced fibrosis and Obuchowski index were not significantly different between ELF and FibroMeter . Algorithms using first ELF or FibroMeter and then liver biopsy in case of undetermined diagnosis provided high diagnostic accuracy for advanced fibrosis: 90% sensitivity, 90% specificity, 93% negative predictive value, 85% positive predictive value, and 90% correct classification. In these algorithms, the rate of liver biopsy was 45.3% with ELF versus 39.3% with FibroMeter (P = .065).

Conclusions: ELF and FibroMeter have equal accuracy and perform better than the simple FIB4 and NFS tests for the non-invasive diagnosis of advanced liver fibrosis in patients with NAFLD from tertiary care centres.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.15529DOI Listing
December 2019

Apparent resistance to thyroid hormones: From biological interference to genetics.

Ann Endocrinol (Paris) 2019 Nov 26;80(5-6):280-285. Epub 2019 Jul 26.

Laboratoire de biochimie et biologie moléculaire, CHU Angers, 49933 Angers cedex 9, France; Unité mixte de recherche MITOVASC, CNRS 6015-Inserm U1083, université d'Angers, 49100 Angers, France; Centre de référence des maladies rares de la thyroïde et des récepteurs hormonaux, CHU Angers, 49933 Angers, France.

Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ando.2019.06.005DOI Listing
November 2019

A Prospective, Observational Study of Conversion From Immediate- to Prolonged-Release Tacrolimus in Renal Transplant Recipients in France: The OPALE Study.

Ann Transplant 2019 Sep 3;24:517-526. Epub 2019 Sep 3.

Nephrology and Transplantation Unit, Cavale Blanche's Hospital, Brest, France.

BACKGROUND Potential benefits of once-daily, prolonged-release tacrolimus over the immediate-release formulation include improved adherence to immunosuppressives post transplantation. An observational study was performed to characterize real-world practice surrounding conversion from immediate- to prolonged-release tacrolimus in kidney transplant recipients. MATERIAL AND METHODS We performed a prospective, observational study of renal transplant recipients converted from immediate- to prolonged-release tacrolimus capsules. Conversion took place at the baseline visit, within the first 6 months of transplantation (early conversion group) or between 6 and 12 months of transplantation (late conversion group). Data collection was performed at routine follow-up at 6 and 12 months. Endpoints included conversion ratio from immediate- to prolonged-release tacrolimus, reasons for conversion, additional visits due to conversion, safety, and tolerability. RESULTS The analysis population comprised 591 patients. Baseline characteristics were similar between the 2 groups. The mean conversion ratio of the daily dose of tacrolimus was 0.98±0.17 in the early group and 0.99±0.09 in the late group. Time from conversion (mean ±SD) to first measurement of trough tacrolimus blood concentration was 12.1±11.6 and 27.6±26.7 days in the early and late groups, respectively. The highest number of additional visits required was 6 in the early conversion group, in 3 patients (0.7%), and 3 in the late conversion group, in 2 patients (1.6%). Conversion from immediate- to prolonged-release tacrolimus was associated with a very low rate of graft rejection. CONCLUSIONS Favorable clinical outcomes and safety profiles were observed with conversion from immediate- to prolonged-release tacrolimus over 1 year following renal transplantation, with no marked differences between the early and late conversion groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AOT.916043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752107PMC
September 2019

A Prospective, Observational Study of Conversion From Immediate- to Prolonged-Release Tacrolimus in Renal Transplant Recipients in France: The OPALE Study.

Ann Transplant 2019 Sep 3;24:517-526. Epub 2019 Sep 3.

Nephrology and Transplantation Unit, Cavale Blanche's Hospital, Brest, France.

BACKGROUND Potential benefits of once-daily, prolonged-release tacrolimus over the immediate-release formulation include improved adherence to immunosuppressives post transplantation. An observational study was performed to characterize real-world practice surrounding conversion from immediate- to prolonged-release tacrolimus in kidney transplant recipients. MATERIAL AND METHODS We performed a prospective, observational study of renal transplant recipients converted from immediate- to prolonged-release tacrolimus capsules. Conversion took place at the baseline visit, within the first 6 months of transplantation (early conversion group) or between 6 and 12 months of transplantation (late conversion group). Data collection was performed at routine follow-up at 6 and 12 months. Endpoints included conversion ratio from immediate- to prolonged-release tacrolimus, reasons for conversion, additional visits due to conversion, safety, and tolerability. RESULTS The analysis population comprised 591 patients. Baseline characteristics were similar between the 2 groups. The mean conversion ratio of the daily dose of tacrolimus was 0.98±0.17 in the early group and 0.99±0.09 in the late group. Time from conversion (mean ±SD) to first measurement of trough tacrolimus blood concentration was 12.1±11.6 and 27.6±26.7 days in the early and late groups, respectively. The highest number of additional visits required was 6 in the early conversion group, in 3 patients (0.7%), and 3 in the late conversion group, in 2 patients (1.6%). Conversion from immediate- to prolonged-release tacrolimus was associated with a very low rate of graft rejection. CONCLUSIONS Favorable clinical outcomes and safety profiles were observed with conversion from immediate- to prolonged-release tacrolimus over 1 year following renal transplantation, with no marked differences between the early and late conversion groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AOT.916043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752107PMC
September 2019

Hemodialysis vascular graft as a focus of persistent Q fever.

Infection 2018 Dec 27;46(6):881-884. Epub 2018 Oct 27.

Department of Nephrology, AP-HM Hôpital de la Conception, Aix-Marseille University, 147 Boulevard Baille, 13005, Marseille, France.

Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s15010-018-1206-5DOI Listing
December 2018

Hemodialysis vascular graft as a focus of persistent Q fever.

Infection 2018 Dec 27;46(6):881-884. Epub 2018 Oct 27.

Department of Nephrology, AP-HM Hôpital de la Conception, Aix-Marseille University, 147 Boulevard Baille, 13005, Marseille, France.

Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s15010-018-1206-5DOI Listing
December 2018

[Kidney transplantation from Maastricht III donors after circulatory death, overview of the situation in France].

Soins 2018 Jun;63(826):36-38

Direction médicale et scientifique, Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La Plaine cedex, France.

Organ retrieval from deceased donors after controlled circulatory arrest improves access to kidney transplantation as a complement to brain dead donors. Authorised since 2014, they represent a real opportunity for patients awaiting a kidney transplant. The initial national results of the French protocol are encouraging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soin.2018.04.010DOI Listing
June 2018

Factors associated with Health-Related Quality of Life in Kidney Transplant Recipients in France.

BMC Nephrol 2018 04 27;19(1):99. Epub 2018 Apr 27.

Laboratoire de Santé Publique, Faculté de Médecine, Université Aix-Marseille, 3279, Marseille, EA, France.

Background: Health-Related Quality of Life (HRQoL) assessment after kidney transplantation has become an important tool in evaluating outcomes. This study aims to identify the associated factors with HRQoL among a representative sample size of Kidney Transplant Recipients (KTR) at the time of their inclusion in the study.

Methods: Data of this cross-sectional design is retrieved from a longitudinal study conducted in five French kidney transplant centers in 2011, and included KTR aged 18 years with a functioning graft for at least 1 year. Measures include demographic, psycho-social and clinical characteristics. To evaluate HRQoL, the Short Form-36 Health Survey (SF-36) and a HRQoL instrument for KTR (ReTransQol) were administered. Multivariate linear regression models were performed.

Results: A total of 1424 patients were included, with 61.4% males, and a mean age of 55.7 years (±13.1). Demographic and clinical characteristics were associated with low HRQoL scores for both questionnaires. New variables were found in our study: perceived poor social support and being treated by antidepressants were associated with low scores of Quality of Life (QoL), while internet access was associated with high QoL scores.

Conclusion: The originality of our study's findings was that psycho-social variables, particularly KTR treated by antidepressants and having felt unmet needs for any social support, have a negative effect on their QoL. It may be useful to organize a psychological support specifically adapted for patients after kidney transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-018-0893-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921567PMC
April 2018

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

Hepatol Commun 2018 04 5;2(4):455-466. Epub 2018 Mar 5.

HIFIH Laboratory Angers University, Bretagne Loire University Angers France.

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter) with those of a test targeted for cirrhosis (CirrhoMeter). In the derivation CHC population, we first compared Multi-FibroMeter to FibroMeter and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter and FibroMeter were the following: cirrhosis AUROC, 0.906 versus 0.878 ( 0.001; versus CirroMeter, 0.897, 0.014); Obuchowski index, 0.795 versus 0.791 ( 0.059); classification, 86.0% versus 82.1% ( 0.001); significant fibrosis AUROC, 0.833 versus 0.832 ( 0.366). Multi-FibroMeter had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi-FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ ( 0.938). Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single-targeted blood tests. ( 2018;2:455-466).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880198PMC
April 2018

LC-MSMS assays of urinary cortisol, a comparison between four in-house assays.

Clin Chem Lab Med 2018 06;56(7):1109-1116

Department of Biochemistry, INSERM U1235 University Hospital of Nantes, Nantes, France.

Background: Twenty-four hour urinary free cortisol (UFC) determination can be used for screening and follow-up of Cushing syndrome (CS). As immunoassay methods lack specificity for UFC measurement, the use of high-performance liquid chromatography coupled to mass spectrometer (LC-MSMS) is recommended. The aim of our study was to compare UFC results using four LC-MSMS methods performed in four independent laboratories in order to evaluate interlaboratory agreement.

Methods: Frozen aliquots of 24-h urine samples (78 healthy volunteers and 20 patients with CS) were sent to four different laboratories for analysis. Following liquid-liquid or solid-liquid extraction, UFC were determined using four different LC-MSMS assay.

Results: UFC intra- and interassays variation coefficients were lower than 10% for each centre. External quality control results were not significantly different. UFC normal ranges (established from healthy volunteers) were 17-126, 15-134, 12-118 and 27-157 nmol/day, respectively. Classification of UFC from healthy volunteers and patients with CS using a 95th percentile threshold was similar. However, for extreme UFC values (<50 or >270 nmol/day), negative or positive bias was noted.

Conclusions: Even for highly specific methods such as LC-MSMS, variations of results can be found depending on analytical process. Validation of LC-MSMS methods including determination of the reference range is essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2017-0806DOI Listing
June 2018

A French Cohort Study of Kidney Retransplantation after Post-Transplant Lymphoproliferative Disorders.

Clin J Am Soc Nephrol 2017 Oct 17;12(10):1663-1670. Epub 2017 Aug 17.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Post-transplant lymphoproliferative disorders arising after kidney transplantation portend an increased risk of morbidity and mortality. Retransplantation of patients who had developed post-transplant lymphoproliferative disorder remains questionable owing to the potential risks of recurrence when immunosuppression is reintroduced. Here, we investigated the feasibility of kidney retransplantation after the development of post-transplant lymphoproliferative disorder.

Design, Setting, Participants, & Measurements: We reviewed the data from all patients who underwent kidney retransplantation after post-transplant lymphoproliferative disorder in all adult kidney transplantation centers in France between 1998 and 2015.

Results: We identified a total of 52 patients with kidney transplants who underwent 55 retransplantations after post-transplant lymphoproliferative disorder. The delay from post-transplant lymphoproliferative disorder to retransplantation was 100±44 months (28-224); 98% of patients were Epstein-Barr virus seropositive at the time of retransplantation. Induction therapy for retransplantation was used in 48 patients (, 17 [31%] patients received thymoglobulin, and 31 [57%] patients received IL-2 receptor antagonists). Six patients were also treated with rituximab, and 53% of the patients received an antiviral drug. The association of calcineurin inhibitors, mycophenolate mofetil, and steroids was the most common maintenance immunosuppression regimen. Nine patients were switched from a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. One patient developed post-transplant lymphoproliferative disorder recurrence at 24 months after retransplantation, whereas post-transplant lymphoproliferative disorder did not recur in 51 patients.

Conclusions: The recurrence of post-transplant lymphoproliferative disorder among patients who underwent retransplantation in France is a rare event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.03790417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628715PMC
October 2017

Thyroglobulin assay in fluids from lymph node fine needle-aspiration washout: influence of pre-analytical conditions.

Ann Biol Clin (Paris) 2017 Apr;75(2):173-180

Laboratoire d'hormonologie, Service de biochimie-toxicologie, CHU de Pontchaillou, Rennes, France, Centre d'investigation clinique plurithématique, Inserm 1414, CHU de Pontchaillou, Rennes, France, Groupe de biologie spécialisée de la Société française de médecine nucléaire, Paris, France.

The aim of this study was to evaluate the pre-analytical factors contributing to uncertainty in thyroglobulin measurement in fluids from fine-needle aspiration (FNA) washout of cervical lymph nodes. We studied pre-analytical stability, in different conditions, of 41 samples prepared with concentrated solutions of thyroglobulin (FNA washout or certified standard) diluted in physiological saline solution or buffer containing 6% albumin. In this buffer, over time, no changes in thyroglobulin concentrations were observed in all storage conditions tested. In albumin free saline solution, thyroglobulin recovery rates depended on initial sample concentrations and on modalities of their conservation (in conventional storage tubes, recovery mean was 56% after 3 hours-storage at room temperature and 19% after 24 hours-storage for concentrations ranged from 2 to 183 μg/L; recovery was 95%, after 3 hours or 24 hours-storage at room temperature, for a concentration of 5,656 μg/L). We show here that these results are due to non-specific adsorption of thyroglobulin in storage tubes, which depends on sample protein concentrations. We also show that possible contamination of fluids from FNA washout by plasma proteins do not always adequately prevent this adsorption. In conclusion, non-specific adsorption in storage tubes strongly contributes to uncertainty in thyroglobulin measurement in physiological saline solution. It is therefore recommended, for FNA washout, to use a buffer containing proteins provided by the laboratory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/abc.2017.1225DOI Listing
April 2017
-->