Publications by authors named "Karine Moreau"

29 Publications

  • Page 1 of 1

Pulmonary Tuberculosis and Management of Contact Patients in a Department of Nephrology and Kidney Transplantation.

Int J Infect Dis 2021 May 21. Epub 2021 May 21.

Department of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, France; Immunoconcept, CNRS UMR 5164, Bordeaux University, Bordeaux, France.

Objectives: To describe the investigation, follow-up, management and outcomes in a cohort of chronic kidney disease and kidney transplant recipients exposed to a case of pulmonary tuberculosis.

Methods: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with an evidence of latent tuberculous infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay.

Results: 130 patients with chronic kidney disease and 180 kidney transplant recipients were identified as contacts and followed-up over a two-year period.Only few vulnerable high-priority contacts received an anti-tuberculosis treatment, including the 2 (100%)highly exposed patients in circle 1, 11/78(14.1%)chronic kidney disease patients and 4/142 (2.8%) kidney transplant recipients in circle 2, and10/52 (19.2%) chronic kidney disease patients and 2/36 (5.6%) kidney transplant recipients in circle 3;all having a positive interferon-gamma release assay result. No incident case of tuberculosis disease occurred.

Conclusions: These findings suggest that latent tuberculosis treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2 with a negative interferon-gamma release assay in countries with low prevalence of tuberculosis.
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http://dx.doi.org/10.1016/j.ijid.2021.05.045DOI Listing
May 2021

Benefit of a pharmacist-led intervention for medication management of renal transplant patients: a controlled before-and-after study.

Ther Adv Chronic Dis 2021 5;12:20406223211005275. Epub 2021 Apr 5.

CHU Bordeaux, Pharmacy, Bordeaux, Pessac, France Univ. Bordeaux, INSERM U1034, Bordeaux, France.

Aims: To assess the effect of a pharmacist-led intervention, using Barrows cards method, during the first year after renal transplantation, on patient knowledge about their treatment, medication adherence and exposure to treatment in a French cohort.

Methods: We conducted a before-and-after comparative study between two groups of patients: those who benefited from a complementary pharmacist-led intervention [intervention group (IG),  = 44] those who did not [control group (CG),  = 48]. The pharmacist-led intervention consisted of a behavioral and educational interview at the first visit (visit 1). The intervention was assessed 4 months later at the second visit (visit 2), using the following endpoints: treatment knowledge, medication adherence [proportion of days covered (PDC) by immunosuppressive therapy] and tacrolimus exposure.

Results: At visit 2, IG patients achieved a significantly higher knowledge score than CG patients (83.3% 72.2%,  = 0.001). We did not find any differences in treatment exposure or medication adherence; however, the intervention tended to reduce the proportion of non-adherent patients with low knowledge scores. Using the PDC by immunosuppressive therapy, we identified 10 non-adherent patients (10.9%) at visit 1 and six at visit 2.

Conclusions: Our intervention showed a positive effect on patient knowledge about their treatment. However, our results did not show any improvement in overall medication adherence, which was likely to be because of the initially high level of adherence in our study population. Nevertheless, the intervention appears to have improved adherence in non-adherent patients with low knowledge scores.
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http://dx.doi.org/10.1177/20406223211005275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024450PMC
April 2021

Evolution of body composition following successful kidney transplantation is strongly influenced by physical activity: results of the CORPOS study.

BMC Nephrol 2021 01 18;22(1):31. Epub 2021 Jan 18.

AURAD Aquitaine, Gradignan, France.

Background: Weight gain (mainly gain of fat mass) occurs quickly after successful kidney transplantation and is associated with metabolic complications (alterations of glycaemic control, hyperlipidaemia). Determinants of weight gain are multifactorial and are mainly related to the transplant procedure itself (glucocorticoid use, increased appetite). In the modern era of transplantation, one challenge is to limit these metabolic alterations by promoting gain of muscle mass rather than fat mass. This prospective study was performed to assess determinants of fat mass, fat-free mass and body cell mass changes after kidney transplantation with a focus on physical activity and nutritional behaviour before and after transplantation.

Methods: Patients were included at the time of listing for deceased donor kidney transplantation. Body composition was determined using dual X-ray absorptiometry and bioimpedance spectroscopy to assess fat mass, fat-free mass and body cell mass (= fat-free mass - extracellular water) at the time of inclusion, 12 months later, and 1, 6, 12 and 24 months after transplantation. Recall dietary data and physical activity level were also collected.

Results: Eighty patients were included between 2007 and 2010. Sixty-five had a complete 24-month follow-up after kidney transplantation. Fat mass, fat-free mass and body cell mass decreased during the waiting period and early after kidney transplantation. The nadirs of body cell mass and fat-free mass occurred at 1 month and the nadir for fat mass occurred at 6 months. Maximum levels of all parameters of body composition were seen at 12 months, after which body cell mass and fat-free mass decreased, while fat mass remained stable. In multivariate analysis, male recipients, higher physical activity level and lower corticosteroid dose were significantly associated with better body cell mass recovery after kidney transplantation.

Conclusions: Lifestyle factors, such as physical activity level, together with low dose of corticosteroids seem to influence body composition evolution following kidney transplantation with recovery of body cell mass. Specific strategies to promote physical activity in kidney transplant recipients should be provided before and after kidney transplantation.
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http://dx.doi.org/10.1186/s12882-020-02214-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814641PMC
January 2021

Efficacy of plasmapheresis and semi-selective immunoadsorption for removal of anti-HLA antibodies.

J Clin Apher 2021 Jun 30;36(3):291-298. Epub 2020 Nov 30.

CNRS UMR 5164, ImmunoConcEpT, Univ. Bordeaux, Bordeaux, France.

Background: In organ transplantation, apheresis is frequently used for removal of anti-HLA antibodies. However, it is unclear whether plasmapheresis (PP) or semi-selective immunoadsorption (IA) should be employed, and the optimal number of apheresis sessions required to reach post-treatment objectives is also unknown.

Methods: We enrolled 43 patients from Bordeaux University Hospital who were treated with PP (n = 29) or IA (n = 14) for antibody-mediated rejection or pre-transplant desensitization. Using Luminex single-antigen flow beads, we assessed the initial mean fluorescence intensity (MFI) of 1416 positive beads with MFIs obtained after 7 to 8 apheresis sessions (extended protocol) and, if a serum was available, after the first four sessions (short protocol).

Results: MFI reduction after extended apheresis protocol was stronger with IA [87% (61%-100%)] than with PP [73% (22%-100%)] (P < .001). Indeed, 59% of the beads had a final MFI < 2000 with IA, whereas only 38% with PP (P < .001). The efficacy of removal depended on initial MFI but not on HLA specificity. A short protocol of apheresis showed excellent results without superiority of IA over PP for antibodies with an initial MFI < 3000. For antibodies showing MFI ≥2000 after four sessions, the residual MFI predicted the effectiveness of four additional sessions.

Conclusion: Monitoring the MFI of anti-HLA antibodies before and during apheresis protocol can guide physicians in the selection of apheresis technique and the number of sessions to be performed.
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http://dx.doi.org/10.1002/jca.21858DOI Listing
June 2021

Poor kidney graft survival in anorexia nervosa patients.

Eat Weight Disord 2021 Jun 15;26(5):1447-1455. Epub 2020 Jul 15.

Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: Anorexia nervosa is a condition associated with poor outcomes in a variety of circumstances such as recurrence of eating disorders, psychiatric disorders, and organ damage.

Objective: In the present study, we first sought to determine the 5-year kidney graft survival in patients with anorexia nervosa and then to evaluate the BMI course and medical complications.

Methods: In this multicenter, retrospective, case-control study, we analyzed the impact of anorexia nervosa on graft outcomes compared to transplant recipients with low or normal BMI.

Results: We enrolled 137 women in this study: 19 with anorexia nervosa, 59 with low BMI (BMI < 18.5 kg/m), and 59 with normal BMI (18.5-24.9 kg/m). Anorexia nervosa was significantly associated with lower graft survival compared to either of the other groups (hazard ratio 5.5 [95% CI 3.4-8.9], p = 0.005); there was no difference in graft survival between patients with low or normal BMI. Cardiovascular complications were more frequent in the anorexia nervosa group (37%) than in patients with low (6%) or normal BMI (7%) (p = 0.001).

Conclusion: We conclude that patients with anorexia nervosa should be considered a high-risk group.

Level Of Evidence: Level III, evidence obtained from well-designed cohort or case-control analytic studies.
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http://dx.doi.org/10.1007/s40519-020-00959-8DOI Listing
June 2021

Plant-based diets to manage the risks and complications of chronic kidney disease.

Nat Rev Nephrol 2020 09 11;16(9):525-542. Epub 2020 Jun 11.

Department of Nephrology, Université de Lyon, Carmen, Hospital Lyon-Sud, Lyon, France.

Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.
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http://dx.doi.org/10.1038/s41581-020-0297-2DOI Listing
September 2020

Unilateral nephrectomy versus renal arterial embolization and technique survival in peritoneal dialysis patients with autosomal dominant polycystic kidney disease.

Nephrol Dial Transplant 2020 02;35(2):320-327

Department of Nephrology, CHU Reims, Reims, France.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy.

Methods: We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters.

Results: More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12-0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0-6.0] in the embolization group versus 8.5 days (IQR 6.0-11.0) in the surgery group.

Conclusions: Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction.
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http://dx.doi.org/10.1093/ndt/gfz200DOI Listing
February 2020

Risk Factors of Early Kidney Graft Transplantectomy.

Transplant Proc 2019 Dec 13;51(10):3309-3314. Epub 2019 Nov 13.

Department of Urology and Kidney Transplantation, University Hospital of Bordeaux, Bordeaux, France.

Background: Kidney allograft explant in the first month after transplant is a major concern for medicosurgical teams specialized in kidney transplantation and unacceptable graft loss in the current shortage. The aim of our study was to evaluate the risk factors of early kidney graft explant.

Methods: We retrospectively analyzed all adult kidney transplantations performed at our center from January 2006 to December 2011. Recipient, donor, and transplant characteristics were collected, as well as operating data and early postoperative complications. Univariate and multivariate logistic regression models were used to determine risk factors of early renal allograft explant.

Results: From a total of 707 kidney transplantations, 28 transplantectomies were performed in the first month following transplantation (3.96%). The average delay in days ± SD was 7.6 ± 10. Eighty-six percent of transplantectomies were due to vascular complications. In multivariate analysis, obesity (odds ratio [OR] = 9.6; 95% confidence interval [CI], 1.63-56.5; P = .0007), range of transplantation (OR = 36.89; 95%CI, 5.5-245; P = .0006), intraoperative complications (OR = 3.99; 95%CI, 1.22-13; P = .026), and early postoperative vascular complications (OR = 85.15; 95%CI, 23.6-306; P < .0001) were independent risk factors. Neither donors nor graft characteristics were significant.

Conclusions: Early renal graft transplantectomies are rare but account for 50% of renal graft loss in the first year. Because obesity, perioperative complications, and early vascular complications are independent factors associated with early transplantectomies, their prevention should be based on meticulous surgery during organ procurement, implantation of the kidney, and on the rehabilitation of future recipients.
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http://dx.doi.org/10.1016/j.transproceed.2019.07.027DOI Listing
December 2019

Lifestyle Intervention Has to Be Part of the Strategy in Kidney Transplant Candidate with Obesity.

Obes Surg 2017 11;27(11):3011-3013

Endocrinology, Diabetology, and Nutrition Department, Neurocentre Magendie Inserm U1215, Univ. Bordeaux, CHU Bordeaux, F-33000, Bordeaux, France.

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http://dx.doi.org/10.1007/s11695-017-2920-2DOI Listing
November 2017

Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature.

PLoS One 2017 21;12(6):e0179406. Epub 2017 Jun 21.

Service d'Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, APHP, Université Pierre et Marie Curie, Paris, France.

Although post-transplant lymphoproliferative disorder (PTLD) is the second most common type of cancer in kidney transplantation (KT), plasma cell neoplasia (PCN) occurs only rarely after KT, and little is known about its characteristics and evolution. We included twenty-two cases of post-transplant PCN occurring between 1991 and 2013. These included 12 symptomatic multiple myeloma, eight indolent myeloma and two plasmacytomas. The median age at diagnosis was 56.5 years and the median onset after transplantation was 66.7 months (2-252). Four of the eight indolent myelomas evolved into symptomatic myeloma after a median time of 33 months (6-72). PCN-related kidney graft dysfunction was observed in nine patients, including six cast nephropathies, two light chain deposition disease and one amyloidosis. Serum creatinine was higher at the time of PCN diagnosis than before, increasing from 135.7 (±71.6) to 195.9 (±123.7) μmol/l (p = 0.008). Following transplantation, the annual rate of bacterial infections was significantly higher after the diagnosis of PCN, increasing from 0.16 (±0.37) to 1.09 (±1.30) (p = 0.0005). No difference was found regarding viral infections before and after PCN. Acute rejection risk was decreased after the diagnosis of PCN (36% before versus 0% after, p = 0.004), suggesting a decreased allogeneic response. Thirteen patients (59%) died, including twelve directly related to the hematologic disease. Median graft and patient survival was 31.7 and 49.4 months, respectively. PCN after KT occurs in younger patients compared to the general population, shares the same clinical characteristics, but is associated with frequent bacterial infections and relapses of the hematologic disease that severely impact the survival of grafts and patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479561PMC
October 2017

[Common therapeutic approaches of sarcopenia in the elderly and uremic myopathy].

Nephrol Ther 2017 Dec 9;13(7):511-517. Epub 2017 Jun 9.

Service de néphrologie transplantation dialyse, hôpital Pellegrin, CHU de Bordeaux, place Amélie-Raba-Léon, 33000 Bordeaux, France.

The gradual loss of weight and function of muscle in patients with chronic kidney disease as in the elderly impacts the quality of life. Early management should help slow the functional limitation. Physical activity is the first therapy to propose that ensures stability of muscle mass and improved function. Resistance training programs have proven effective but are not yet widely available in nephrology units. The nutritional management should not be forgotten because there is a resistance to anabolism and protein intake should be involved in physical activity program. Associated treatments should not be neglected: vitamin D, anti-inflammatory, androgens. Some are still under evaluation. Therapeutic option, tomorrow, could be anti-myostatin antibodies and glitazones.
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http://dx.doi.org/10.1016/j.nephro.2016.12.004DOI Listing
December 2017

Skin autofluorescence in acute kidney injury.

Crit Care 2017 Feb 9;21(1):24. Epub 2017 Feb 9.

Endocrinologie-Nutrition, Université de Bordeaux, 33000, Bordeaux, France.

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http://dx.doi.org/10.1186/s13054-017-1598-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299740PMC
February 2017

Role of T3SS-1 SipD Protein in Protecting Mice against Non-typhoidal Salmonella Typhimurium.

PLoS Negl Trop Dis 2016 12 19;10(12):e0005207. Epub 2016 Dec 19.

Service de Pharmacologie et Immunoanalyse (SPI), CEA, INRA, Université Paris-Saclay, Gif-sur-Yvette, France.

Background: Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine.

Principal Findings: We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant.

Conclusions And Significance: Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality.
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http://dx.doi.org/10.1371/journal.pntd.0005207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167260PMC
December 2016

Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study.

Transplantation 2016 10;100(10):2099-2106

1 Hôpital Pasteur, Nice, France.2 Hôpital Saint Eloi, Montpellier, France.3 CHU Nantes, Nantes, France.4 Hôpital Rangueil, Toulouse, France.5 Hôpital Necker, Paris, France.6 Hôpital de Jour, Villejuif, France.7 Groupe Hospitalier Henri Mondor, Créteil, France.8 CHU Bordeaux, Bordeaux, France.9 Hôpital Europeen Georges Pompidou, Paris, France.10 CHU Amiens-Picardie, Amiens, France.11 Mapi, Lyon, France.12 Hôpital Claude Huriez, Lille, France.13 Hôpital d'adultes de Brabois, Vandoeuvre Les Nancy, France.

Background: Adherence to immunosuppressive treatments is a major concern in transplanted patients.

Methods: This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once-daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self-administered questionnaires at inclusion and at 3 and 6 months.

Results: Mean age was 52.4 ± 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0-100) was 77.7 (±24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (±26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6.

Conclusions: Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients.
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http://dx.doi.org/10.1097/TP.0000000000001307DOI Listing
October 2016

[Sarcopenia or uremic myopathy in CKD patients].

Nephrol Ther 2016 Apr 17;12(2):71-5. Epub 2015 Nov 17.

Service de néphrologie transplantation dialyse, CHU de Bordeaux, hôpital Pellegrin, place Amélie-Raba-Léon, 33000 Bordeaux, France.

Often underestimated or misunderstood in chronic renal failure (CRF), muscle wasting is nevertheless common and concerns about 50% of dialysis patients. The consequences of this myopathy on quality of life and outcomes of patients are unfavorable, identical to those observed in sarcopenia in elderly subjects with sarcopenia. The similarities between the two situations also concern the symptoms, the underlying muscle damages and the pathogenic mechanisms and may be partly explained by the frequently high age of ESRD patients. Skeletal muscle involvement should be systematically investigated in the IRC patient as in the elderly with sarcopenia to propose as early as possible a treatment of which physical activity and nutritional interventions are the mainstay.
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http://dx.doi.org/10.1016/j.nephro.2015.08.002DOI Listing
April 2016

Evolution of serum and intra-graft donor-specific anti-HLA antibodies in a patient with two consecutive liver transplantations.

Transpl Immunol 2015 Oct 28;33(2):58-62. Epub 2015 Aug 28.

Laboratory of Immunology and Immunogenetics, Bordeaux University Hospital, France; CNRS UMR 5164, CIRID, University of Bordeaux, France. Electronic address:

The current literature suggests that anti-HLA donor-specific antibodies (DSA) may have deleterious effects on liver grafts but there is no proof that they are directly involved in the graft lesions. We report the case of a donor HLA-sensitized patient who needed a second graft 6 months after the first transplantation owing to a progressive cholestatic disease that we could finally attribute to antibody-mediated rejection (AMR). We describe the longitudinal evolution of graft function, tissue histology, serum DSA and, for the first time, intra-graft DSA after elution from biopsies.
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http://dx.doi.org/10.1016/j.trim.2015.08.002DOI Listing
October 2015

Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

Clin Transplant 2015 May 30;29(5):439-46. Epub 2015 Mar 30.

Unité de Transplantation, Service de Néphrologie, Transplantation, Dialyse, CHU de Bordeaux, Bordeaux, France; UMR 5164, CNRS, Bordeaux, France; Université de Bordeaux, Bordeaux, France.

Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events.
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http://dx.doi.org/10.1111/ctr.12535DOI Listing
May 2015

Body composition in 98 patients awaiting kidney transplantation.

Nutrition 2014 Feb;30(2):186-91

AURAD Aquitaine, Gradignan, France.

Objective: Recent data suggest that the nutritional status of patients who are on the waiting list for kidney transplantation, influence outcomes after renal transplantation. Body composition (BC) analysis is rarely included in pretransplant evaluation. The aim of this study was to determine how alteration of the BC of these patients could influence pretransplant and post-transplant care.

Methods: We compared the BC of French patients on a waiting list for kidney transplantation to a sex- and age-matched healthy, European control population. Patients were included when listed for kidney grafting in a prospective longitudinal study (CORPOS). Biological nutritional parameters, fat free mass (FFM) and fat mass (FM) estimated by dual-energy x-ray absorptiometry (DXA) were assessed on the day of wait-list registration. FFM and FM index (FFMi - FMi) are the ratio of FFM and FM to height squared. Results are expressed as median (range). These indexes were compared with previous study values used as a normal range in nutritional assessment and clinical practice.

Results: The study included 28 women and 70 men aged 25.3 to 65.9 y. Body mass index ranged from 16.8 kg/m² to 39.4 kg/m². Compared with controls, FMi was higher in women (10.6 kg/m² [3.7-18.6 kg/m²]) than in men (8.1 kg/m² [3.5-13.3 kg/m²] in M) and FFMi was lower in women (14.3 kg/m² [11.8-21.4 kg/m²]) than in men (17.9 kg/m² [13.9-24.2 kg/m²]) (P < 0.01), reflecting an abnormal distribution of body compartments. All biological parameters were within the normal range.

Conclusion: BC abnormalities, which can only be detected with the use of DXA, are present in patients on a kidney transplantation waiting list. Detection of these abnormalities could influence the post-transplantation survey in order to prevent the frequent risk for developing metabolic complications after the procedure.
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http://dx.doi.org/10.1016/j.nut.2013.07.018DOI Listing
February 2014

Protein redistribution from skeletal muscle to splanchnic tissue on fasting and refeeding in young and older healthy individuals.

J Am Med Dir Assoc 2013 Sep;14(9):696-704

INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, UNH, Clermont-Ferrand, France; CRNH Auvergne, Clermont-Ferrand, France.

Background: During aging, a shift of protein metabolism from muscle to splanchnic tissue contributes to increased muscle protein loss after a period of metabolic stress (eg, fasting).

Objective: To study the adaptation of protein metabolism in the whole body and tissue (ie, skeletal muscle and splanchnic area) to metabolic stress, such as short-term fasting and refeeding, in aged people.

Design And Participants: We studied splanchnic and muscle protein metabolism after 38 hours of fasting and refeeding in 7 young (5 men/2 women, 24.4 ± 2.0 years) and 8 elderly individuals (6 men/2 women, 70.6 ± 3.1 years).

Measurements: We used intravenous (IV) L-[(13)C6]phenylalanine, IV L-[(2)H3]leucine, and oral L-[(13)C1]leucine to obtain (1) whole-body protein kinetics, (2) muscle and albumin fractional synthesis rate (FSR, %/d; (13)C6-Phe, and (13)C1-Leu), and (3) splanchnic extraction during fasting and refeeding (%, (2)H3- and (13)C1-Leu).

Results: Whole-body protein breakdown was activated during fasting in young and older individuals (P < .01 vs fasted state). Muscle FSR remained unchanged in both groups and not stimulated by refeeding in either group with either IV (13)C Phe or oral (13)C Leu, probably because of high plasma levels of essential amino acids (EAAs) and branched-chain amino acids (BCAAs). Splanchnic extraction of leucine was 42% higher in the elderly individuals (P = .03 vs young) and was associated with an increased albumin synthesis rate in elderly individuals in the fed state (P < .05 vs young).

Conclusion: Splanchnic protein metabolism is modified by age, but this metabolic change is not associated with a lower synthesis rate of muscle protein, provided high plasma levels of essential EAAs are maintained. Our data also suggest that splanchnic protein synthesis is a metabolic priority during recovery after metabolic stress in healthy elderly persons and that it might be even more affected in polymedicated older individuals having chronic diseases.
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http://dx.doi.org/10.1016/j.jamda.2013.06.005DOI Listing
September 2013

Pathogen-free screening of bacteria-specific hybridomas for selecting high-quality monoclonal antibodies against pathogen bacteria as illustrated for Legionella pneumophila.

J Immunol Methods 2013 May 27;391(1-2):81-94. Epub 2013 Feb 27.

CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, CEA Saclay, 91191 Gif-sur-Yvette, France.

Antibodies are potent biological tools increasingly used as detection, diagnostic and therapeutic reagents. Many technological advances have optimized and facilitated production and screening of monoclonal antibodies. We report here an original method to screen for antibodies targeting biosafety level 2 or 3 pathogens without the fastidious handling inherent to pathogen use. A double ELISA screening was performed using as coated antigen transformed Escherichia coli expressing at its surface a protein specific to the pathogenic bacteria versus control untransformed E. coli. This method was applied to Legionella, using the surface-exposed Mip protein (macrophage infectivity potentiator). This screening proved to be an excellent means of selecting mAbs that bind Legionella pneumophila 1 surface-exposed Mip protein. This method also appears more biologically relevant than screening using the recombinant Mip protein alone and less tedious than a test performed directly on Legionella bacteria. We obtained 21 mAbs that bind strongly to L. pneumophila serogroups 1 to 13, and we validated their use in a rapid ELISA (performed in 4.5 h) and an immunochromatographic test (20 min).
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http://dx.doi.org/10.1016/j.jim.2013.02.012DOI Listing
May 2013

Interpretation of positive flow cytometric crossmatch in the era of the single-antigen bead assay.

Transplantation 2011 Mar;91(5):527-35

CHU Bordeaux, Hôpital Pellegrin, Nephrology, Place Amélie Raba Léon, Bordeaux, France.

Background: Prognosis of renal transplants with positive flow cytometric crossmatch (FCXM) remains controversial.

Methods: We analyzed the outcome of these kidney transplant recipients by human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major histocompatibility complex classes I and II. We compared them with controls with a negative FCXM.

Results: Forty-five patients consecutively transplanted with a positive FCXM had significantly more acute rejection episodes than the control patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B-cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5, P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining FCXM-positive patients displayed short-term outcomes similar to controls. The presence of HLA-DSA detected only by the SAB assay in the context of a negative FCXM crossmatch was not associated with increased risk of acute rejection.

Conclusion: Identification of HLA-DSA in D0 sera by the two sensitive techniques FCXM and SAB assay indicates which patients are at highest risk of subsequent acute allograft rejection and chronic allograft dysfunction.
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http://dx.doi.org/10.1097/TP.0b013e31820794bbDOI Listing
March 2011

[Post-transplantation diabetes mellitus].

Authors:
Karine Moreau

Nephrol Ther 2006 Jan;2 Suppl 1:S71-6

Département de néphrologie, unité de néphrologie et transplantation rénale Professeur-Merville, hôpital Pellegrin-Tripode, place Amélie-Raba-Léon, 33076 Bordeaux, France.

Post-transplant diabetes mellitus is a frequent and serious complication after organ transplantation. Its ethiopathogenesis is complex, with interaction between intrinsic factors (older age, body mass index, individual and family history, hepatitis C virus infection) and graft related factors (immunosuppressive regimen, HLA status). In kidney transplant recipients, new onset diabetes mellitus is associated with an adverse effect upon patient survival, with an increased incidence of infectious and cardiovascular complications. Furthemore, post transplant diabetes mellitus clearly affects long-term allograft survival. Management of new onset diabetes mellitus after transplantation includes: screening for risk factors before transplantation (to propose lifestyle modifications and adaptation of immunosuppressive therapy); regular monitoring of glycemia after transplantation; non pharmacologic and pharmacologic therapies associated with management of others cardiovascular risk factors (hypertension, dyslipidemias).
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January 2006

Long-term evolution of body composition after renal transplantation: 5-year survey.

J Ren Nutr 2006 Oct;16(4):291-9

Département de Néphrologie et de Transplantation Rénale, Centre Hospitalier Universitaire, Bordeaux, France.

Background: Thanks to advancements in immunosuppression, patients are living longer with kidney transplants, and nonimmunologic factors (particularly nutritional) have become a major source of morbidity and mortality after successful kidney transplantation (KTx). In this current study, we have prospectively assessed, in a cohort of kidney transplant recipients (KTR), the course of some nonimmunologic factors liable to hinder the long-term outcome of KTR.

Methods: Forty-four consecutive KTR with stable functioning grafts received dietary recommendations and were on the lowest effective dose of steroids. Biochemical nutritional markers, C-reactive protein, lipid profile, and body composition determined by dual-energy X-ray absorptiometry were studied over the first year, 2 years, and 5 years after KTx.

Results: No patients died during the follow-up. All patients but 2 were considered normotensive. Clinical diabetes developed in 3 patients. Visceral proteins stabilized at a normal range after the first year. Most of the patients normalized their inflammatory status. A significant improvement in lipid profile was observed. Female patients had a significant increase of weight (13.5%), mainly because of an increase in fat mass: 3.4 kg (19.4%) at 1 year and 5.6 kg (29.7%) at 2 years. In male patients, body composition remained stable and close to baseline values. The evolution of bone mass varied according to gender, total corticoid doses, and calcineurin inhibitors. Patients on low doses of steroids normalized their Z-score over the 5-year period. The increase in bone mass (paired t-test, P = .006) was only significant in patients treated with tacrolimus (analysis of variance for repeated measures, P < .001).

Conclusions: Simple measures and dietary intervention to prevent or correct nonimmunologic disorders should permit improvement of long-term morbidity and mortality of KTR without compromising the functional outcome of their transplant.
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http://dx.doi.org/10.1053/j.jrn.2006.04.026DOI Listing
October 2006

Verapamil and mild hyperkalemia in hemodialysis patients: a potentially hazardous association.

Hemodial Int 2006 Apr;10(2):170-2

Service de néphrologie et d'hémodialyse, CHU Pellegrin, Bordeaux, France.

During the past 3 years, 3 patients undergoing intermittent hemodialysis (or about to do so) in our hospital developed a third-degree atrioventricular block while being treated with verapamil for blood pressure or supraventricular arrhythmia. In the 3 cases, mild hyperkalemia was concomitant. The medical history of these patients revealed no intrinsic cause of atrioventricular conduction disturbance. We report herein the 3 cases and draw attention to the risks of atrioventricular block in this particular context.
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http://dx.doi.org/10.1111/j.1542-4758.2006.00090.xDOI Listing
April 2006

Splanchnic tissues play a crucial role in uremic glucose intolerance.

J Ren Nutr 2003 Jul;13(3):212-8

Service de Nutrition et Diabétologie, USN, Hôpital Haut-Lévêque, Pessac, France.

Objective: Determine the mechanism of glucose intolerance in chronically uremic subjects.

Design: Comparison of doubly labeled oral glucose tolerance tests.

Subjects: Seven nondialyzed chronically uremic subjects (creatinine, 420 +/- 104 micromol/L) and 7 healthy subjects, matched for age and body mass index.

Intervention: Plasma glucose was labeled by an infusion of dideuterated glucose started 120 minutes before ingestion of 1 g/kg of naturally 13C-enriched corn starch glucose. Glucose levels and oxidation were monitored for 330 minutes after glucose ingestion.

Results: Uremic subjects had normal fasting plasma glucose levels and impaired glucose tolerance with high plasma insulin (P <.001 versus controls). Glucose tolerance was impaired because of an increased total rate of appearance of glucose (cumulated on 330 minutes: uremic, 1,231 +/- 42 mg/kg/330 min, controls, 1,031 +/- 64; P <.05). Peripheral glucose uptake was increased (P <.05) because of an increased nonoxidative disposal (P =.051).

Conclusions: Although peripheral glucose uptake resisted the stimulatory effect of the high insulin levels, glucose tolerance was impaired through splanchnic metabolic disturbances: reduced splanchnic glucose uptake and increased endogenous glucose production. The respective contribution of these abnormalities remains to be determined.
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http://dx.doi.org/10.1016/s1051-2276(03)00071-2DOI Listing
July 2003

Alterations of sensory perceptions in healthy elderly subjects during fasting and refeeding. A pilot study.

Gerontology 2002 Jan-Feb;48(1):39-43

University of Ulster at Coleraine, Cromore Road, Co. Derry, Northern Ireland.

Background: Sensory perception losses may contribute to age-related malnutrition by affecting food selection and consumption.

Objective: To determine the effects of a 36-hour fast followed by a 6-hour refeeding period on sensory perceptions in 7 healthy elderly subjects (65-80 years of age) and 6 healthy young subjects (18-35 years of age).

Methods: Self-perceived hunger and olfactory ratings were recorded on visual analogue scales in response to three different classes of odorant stimuli (salt, sweet and sour). Odorant stimuli were administered three times during the study, twice during the fasting period (12 and 24 h fasted) and once at the end of the re-nutrition period.

Results: A significant difference was found between the two groups for the self-perceived hunger ratings in response to the sour stimuli. A significant difference was observed between the two groups for olfactory ratings as regards the salt and sour odorant stimuli. Among the metabolic changes associated with fasting and refeeding, blood glucose was significantly related (r(2) = 0.97, p = 0.001) to the perception of hunger in the control group subjects, but no such relationship was found for the elderly subjects (r(2) = 0.16, p = NS).

Conclusion: (1) Self-perceived hunger and olfactory ratings are specifically affected in healthy elderly. (2) Nutritional status can modulate sensory perceptions in elderly and young during the transition from fasting to refeeding.
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http://dx.doi.org/10.1159/000048923DOI Listing
April 2002
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