Publications by authors named "Georges Mourad"

103 Publications

Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation.

Clin Kidney J 2020 Oct 26;13(5):791-802. Epub 2020 Apr 26.

Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France.

Background: The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT.

Methods: The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFR) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients.

Results: Both 3-month eGFR and proteinuria were independent predictors of return to dialysis (all P < 0.05) and there was a strong correlation between eGFR at 3 and 12 months (Spearman's ρ = 0.76). The predictive accuracy of the 3-month eGFR was within a similar range and did not differ significantly from the 12-month eGFR in either the derivation cohort [C-index 62.6 (range 57.2-68.1) versus 66.0 (range 60.1-71.9), P = 0.41] or the validation cohort [C-index 69.3 (range 66.4-72.1) versus 71.7 (range 68.7-74.6), P = 0.25].

Conclusion: The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
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http://dx.doi.org/10.1093/ckj/sfaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577768PMC
October 2020

Distribution of Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity.

Front Immunol 2020 2;11:919. Epub 2020 Jun 2.

Department of Nephrology, Dialysis and Transplantation, Montpellier University Hospital, University of Montpellier, Montpellier, France.

Donor-specific antibodies (DSAs) are the main risk factor for antibody-mediated rejection (ABMR) and graft loss but could have variable pathogenicity according to their IgG subclass composition. Luminex-based test might lack sensitivity for the detection of IgG subclasses and this test does not allow quantifying the relative abundance of each IgG subclass. We investigated the precise repartition of each DSA subclass and their role in ABMR occurrence and severity, using an innovative mass spectrometry-based method. Between 2014 and 2018, we enrolled 69 patients who developed DSA ( = 29 without ABMR, and = 40 with ABMR) in two transplant centers. All IgG subclasses were detected in every samples tested: 62.7% were IgG1, 26.6% were IgG2, 6.6% were IgG3, and 4.2% were IgG4. The IgG3 proportion was significantly higher in the ABMR+ compared to the ABMR- group (8.4% vs. 5.6%, = 0.003). The proportion of IgG1, IgG2, and IgG4 of DSA was similar between the two groups. Higher IgG3 level was associated with higher C4d deposition, higher microvascular inflammation scores, and glomerular filtration rate decline >25%. IgG3 proportion was not correlated with DSA MFI. Multivariate analysis showed that proteinuria and high level of IgG3 DSA were the only two factors independently associated with ABMR. In conclusion, DSA are always composed of the four IgG subclasses, but in different proportions. High IgG3 proportion is associated with ABMR occurrence and severity and with poorer outcome, independently of DSA MFI.
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http://dx.doi.org/10.3389/fimmu.2020.00919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326073PMC
April 2021

Comparison of machine perfusion versus cold storage in kidney transplant recipients from expanded criteria donors: a cohort-based study.

Nephrol Dial Transplant 2020 06;35(6):1043-1070

Centre Hospitalier Universitaire de Nantes, Nantes, France.

Background: Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys.

Methods: The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan-Meier estimators, weighted on the propensity score, were used to study the times-to-events.

Results: Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4-6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7-6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h.

Conclusions: Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.
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http://dx.doi.org/10.1093/ndt/gfz175DOI Listing
June 2020

Induction Therapy in Elderly Kidney Transplant Recipients With Low Immunological Risk.

Transplantation 2020 03;104(3):613-622

Centre de Recherche en Transplantation et Immunologie INSERM UMR1064, Université de Nantes, RTRS "Centaure", Nantes, France.

Background: In nonimmunized patients, similar rejection rates are observed for patients who have undergone thymoglobulin (antithymocyte globulins [ATG]) or basiliximab (BSX) therapy. While ATG may improve delayed graft function, it may also be associated with higher infection rates and malignancy risk. We compared survival and clinical outcomes in elderly recipients with low immunological risk according to their induction therapy.

Methods: We conducted a multicentric study on nonimmunized patients ≥65 years of age receiving a first kidney transplant between 2010 and 2017. The principal outcome was patient and graft survival. Secondary outcomes were cumulative probabilities of infection, first acute rejection episode, malignancy, de novo donor specific antibody, posttransplant diabetes (PTD), cardiac complications, estimated glomerular filtration rate, and occurrence of delayed graft function. Cox, logistic, or linear statistical models were used depending on the outcome studied, and models were weighted on the propensity scores.

Results: Two hundred and four patients were included in the BSX group and 179 in the ATG group with the average age of 71.0 and 70.5 years, respectively. Patient and graft survival at 3 years posttransplantation were 74% (95% CI, 65%-84%) and 68% (95% CI, 60%-78%) in ATG and BSX group, respectively, without significant difference. Occurrence of PTD was significatively higher in BSX group (23% versus 15%, P = 0.04) due to higher trough levels of Tacrolimus on month 3 (9.48 versus 7.30 ng/mL, P = 0.023). There was no difference in other evaluated outcomes.

Conclusions: In elderly recipients, ATG does not lead to poorer outcomes compared with BSX and could permit lower trough levels of Tacrolimus, thus reducing occurrence of PTD.
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http://dx.doi.org/10.1097/TP.0000000000002804DOI Listing
March 2020

C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection.

Front Immunol 2019 8;10:235. Epub 2019 Mar 8.

University of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, France.

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival ( = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.
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http://dx.doi.org/10.3389/fimmu.2019.00235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418012PMC
May 2020

Dynamic predictions of long-term kidney graft failure: an information tool promoting patient-centred care.

Nephrol Dial Transplant 2019 11;34(11):1961-1969

INSERM UMR 1246 - SPHERE, Nantes University, Tours University, Nantes, France.

Background: Informing kidney transplant recipients of their prognosis and disease progression is of primary importance in a patient-centred vision of care. By participating in decisions from the outset, transplant recipients may be more adherent to complex medical regimens due to their enhanced understanding.

Methods: We proposed to include repeated measurements of serum creatinine (SCr), in addition to baseline characteristics, in order to obtain dynamic predictions of the graft failure risk that could be updated continuously during patient follow-up. Adult recipients from the French Données Informatisées et VAlidées en Transplantation (DIVAT) cohort transplanted for the first or second time from a heart-beating or living donor and alive with a functioning graft at 1 year post-transplantation were included.

Results: The model was composed of six baseline parameters, in addition to the SCr evolution. We validated the dynamic predictions by evaluating both discrimination and calibration accuracy. The area under the receiver operating characteristic curve varied from 0.72 to 0.76 for prediction times at 1 and 6 years post-transplantation, respectively, while calibration plots showed correct accuracy. We also provided an online application tool (https://shiny.idbc.fr/DynPG).

Conclusion: We have created a tool that, for the first time in kidney transplantation, predicts graft failure risk both at an individual patient level and dynamically. We believe that this tool would encourage willing patients into participative medicine.
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http://dx.doi.org/10.1093/ndt/gfz027DOI Listing
November 2019

Successful treatment of a associated haemolytic uraemic syndrome by eculizumab.

Clin Kidney J 2019 Feb 20;12(1):106-109. Epub 2018 Mar 20.

Department of Nephrology and Kidney Transplantation, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.

Haemolytic uraemic syndrome (HUS) is a rare complication of invasive infection by (SP-HUS), especially in adults. Here we report an unusual case of a 53-year-old man presenting SP-HUS with severe multivisceral involvement. After failure of supportive care and plasma exchanges, eculizumab (anti-C5 antibody) resulted in a favourable outcome.
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http://dx.doi.org/10.1093/ckj/sfy019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366139PMC
February 2019

Lack of impact of pre-emptive deceased-donor kidney transplantation on graft outcomes: a propensity score-based study.

Nephrol Dial Transplant 2019 05;34(5):886-891

Centre Hospitalier Universitaire de Nantes, Nantes, France.

Background: A significant number of studies have compared graft outcomes between patients with Pre-emptive Kidney Transplantation (PreKT) and patients on Dialysis before their Kidney Transplantation (DiaKT). These studies have suffered from the limitation that the DiaKT group is composed of all the dialysed patients, including those placed on a waiting list at the time of their first dialysis session. This seriously questions the comparability of these patients with those placed on the waiting list a long time before the need for renal replacement therapy. The aim of this study was to precisely evaluate the causal effect of PreKT from deceased donors.

Methods: Data were extracted from the multicentric French DIVAT (Données Informatisées et VAlidées en Transplantation) cohort. The DiaKT group was composed of patients placed on the waiting list with an initial intention of pre-emptive transplantation. Cause-specific Cox models with propensity scores (inverse probability weighting) were used to study the patient and graft outcomes.

Results: Among the 1138 included patients, 554 patients were in the PreKT group. The outcomes of the PreKT group were similar compared with the DiaKT group. In particular, the life expectancy with a functioning graft was 8.51 years [95% confidence interval (CI) 8.20-8.81] for the PreKT recipients versus 8.49 years (95% CI 8.15-8.84) for the DiaKT recipients.

Conclusions: Our results challenge the utility of PreKTs from deceased donors, especially with regard to the consequential increase in the waiting list.
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http://dx.doi.org/10.1093/ndt/gfy317DOI Listing
May 2019

Comparison of graft and patient survival according to the transplantation centre policy for 1-year screening biopsy among stable kidney recipients: a propensity score-based study.

Nephrol Dial Transplant 2019 04;34(4):703-711

INSERM UMR 1246 - SPHERE, Nantes University, Tours University, Nantes, France.

Background: The clinical utility of screening biopsies (SBs) at 1 year post-transplantation is still debated, especially for stable kidney graft recipients. Given the heterogeneity in practices between transplantation centres, the objective of this study was to compare graft and patient survival of stable patients according to whether they were followed up in a transplantation centre with or without a policy for having an SB at 1 year post-transplantation.

Materials: From a French multicentre cohort, we studied 1573 kidney recipients who were alive with stable graft function at 1 year post-transplantation, with no acute rejection in their first year post-transplantation.

Results: Using propensity score-based analyses, we did not observe any significant difference in the relative risk for graft failure between patients from centres with a 1-year SB policy and those from other centres [hazard ratio = 1.15, 95% confidence interval (CI) 0.86-1.53]. The corresponding adjusted survival probability at 8 years post-transplantation was 69% (95% CI 61-74%) for patients from centres with a 1-year SB policy versus 74% (95% CI 67-79%) for those from other centres.

Conclusion: A 1-year SB policy for stable patients may not lead to therapeutical benefits for improved graft and patient survival. Further studies examining the benefits versus the risks of a 1-year SB policy are warranted to demonstrate the long-term utility of this intervention.
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http://dx.doi.org/10.1093/ndt/gfy221DOI Listing
April 2019

Heparin-free renal replacement therapy for chronic hemodialyzed patients at high risk for bleeding: a comparison of on-line predilution hemodiafiltration with conventional hemodialysis.

Hemodial Int 2018 10 10;22(4):463-473. Epub 2018 May 10.

Department of Nephrology, Dialysis, and Transplantation, Univ Montpellier, CHU Montpellier, Lapeyronie Hospital, Montpellier, France.

Background: In chronic hemodialysis patients with high risk of bleeding, optimal anticoagulation of the extracorporeal circuit is challenging. Heparin-free hemodialysis (HD) with heparin-coated AN69ST dialyzer is now considered as a good option and recommended by experts. Predilutional hemodiafiltration (HDF) may represent also a feasible alternative but has been poorly investigated. In this study, our aim was to evaluate the performance of on-line automated predilution heparin-free HDF as compared to conventional heparin-free HD with a heparin-coated membrane.

Methods: We prospectively studied chronic hemodialysis patients at high risk of bleeding consecutively admitted to hospital who underwent heparin-free renal replacement therapy (RRT) in our nephrology department. During 1 year, we routinely used heparin-free HD and on-line HDF in these settings. By using a propensity score, we compared HDF to HD regarding to session failure and efficiency.

Results: One hundred and seventy-nine patients were included in the study. Clotting phenomena necessitating premature termination of RRT sessions were encountered in 19% of them. After propensity score matching, the comparison of 77 HD and 77 HDF sessions showed no significant differences in duration of the sessions and in dialyzer clotting. By multivariate analysis, a blood flow less than 250 mL/min and recent surgery were the only parameters associated with extracorporeal circuit thrombosis.

Conclusion: Heparin-free on-line predilutional HDF is a safe and effective technique for chronic hemodialysis patients with increased bleeding risk. The use of an automatic substitution volume that avoids filters hemoconcentration and of a blood flow above 250 mL/min strongly contribute to the observed performance. Further studies are, however, intended to confirm these results.
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http://dx.doi.org/10.1111/hdi.12668DOI Listing
October 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.
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http://dx.doi.org/10.1186/s12882-018-0893-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921567PMC
April 2018

Preemptive second kidney transplantation is associated with better graft survival compared with non-preemptive second transplantation: a multicenter French 2000-2014 cohort study.

Transpl Int 2018 04 20;31(4):408-423. Epub 2017 Dec 20.

Department of Nephrology and Kidney Transplantation, University Hospital of Nancy, Vandoeuvre-les-Nancy, France.

The impact of preemptive second kidney transplantation (2KT) on graft and patient survival is poorly established. The association between preemptive 2KT (p2KT, N = 93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314) recipients using propensity score methods. During the follow-up, there were 274 returns to dialysis and 134 deaths. p2KT was associated with lower death-censored graft loss (HR = 0.39 [0.18-0.88], P = 0.024) and graft failure from any cause including death (HR = 0.42 [0.22-0.80], P = 0.008). Similar associations were observed for death with a functioning graft, although not reaching statistical significance (HR = 0.47 [0.17-1.26], P = 0.13). There was a significant interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT was not significantly associated with the risk of graft failure from any cause including death in living donor 2KT (P = 0.39), whereas the association was substantial in the deceased donor subset (HR = 0.30 [0.14-0.64], P = 0.002). Of note, the adjusted graft survival of p2KT with deceased donor paralleled that of 2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and 76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study analyzed using propensity scores suggests that p2KT is associated with better graft prognosis.
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http://dx.doi.org/10.1111/tri.13105DOI Listing
April 2018

Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study.

Transpl Int 2017 Sep 15;30(9):893-902. Epub 2017 Jun 15.

Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Lyon, France.

Simultaneous pancreas and kidney transplantation (SPK) is currently the best therapeutic option for patients with type 1 diabetes and terminal renal failure. Renal transplantation restores fertility enabling women to pursue pregnancies. However, scarcity of available data on pregnancy outcomes in SPK impedes fair medical counseling. Medical files of all pregnancies that lasted ≥3 months among recipients of functional SPK performed between 1990 and 2015 in France were retrospectively analyzed. Twenty-six pregnancies in 22 SPK recipients were identified. Main maternal complications included gestational hypertension (53.8%) and infections (50%). Cesarean section was performed in 73% of cases. Overall fetal survival was 92.6% with a mean gestational age of 34.2 ± 3 weeks. Four children (16.7% of live births) had a birth weight <10th percentile. Endocrine pancreas graft function remained stable during pregnancy. An acute kidney rejection occurred in two patients, one of which resulting in graft loss. Kidney and pancreas graft survival was, respectively, 96% and 100% at 1 year postconception and did not differ from controls. Pregnancy in SPK is feasible, but patients should be informed of the risks for the fetus, the mother, and the grafts. Planning of pregnancy in SPK women is key to allow a personalized multidisciplinary monitoring, which represents the most straightforward approach to optimize outcomes.
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http://dx.doi.org/10.1111/tri.12983DOI Listing
September 2017

Standardized Method to Measure Muscle Force at the Bedside in Hemodialysis Patients.

J Ren Nutr 2017 05 17;27(3):194-200. Epub 2017 Mar 17.

PhyMedExp, UMR CNRS 9214, Inserm U1046, University of Montpellier, Montpellier, France; Department of Physiology, University Hospital of Montpellier, University of Montpellier, Montpellier, France.

Objectives: In hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients.

Design: Repeated-measures cross-sectional study.

Setting: Clinical and academic hospital.

Participants: Fifty-three healthy adult subjects (23 males, 36.5 + 12.5 y.o.) and 21 hemodialysis patients (14 males, 72.4 + 13.3 y.o., dialysis vintage 30 + 75.1 months).

Intervention: Not applicable.

Main Outcome Measure: MVF measurements were assessed with belt-stabilized HHD and dynamometer chair, by two independent investigators. The agreement between the two devices would be quantified using the Bland-Altman 95% limits of agreement (LOA) method and the Spearman correlation.

Results: For healthy subjects and hemodialysis patients, Spearman coefficients between belt-stabilized HHD and dynamometer chair were 0.63 and 0.75, respectively (P < .05). In hemodialysis group, reliability was excellent for both the intratester and intertester reliability R = 0.85 (P < .01) and R = 0.90 (P < .01), respectively. In all individuals, the mean difference between the dynamometer chair and the belt-stabilized HHD was -13.07 ± 21.77 N.m. (P < .001). The LOA for the upper and the lower was 29.59 and -55.73 N.m., respectively.

Conclusion: In healthy subjects and in hemodialysis patients, the belt-stabilized HHD dynamometer appears as a valid and reliable method to measure in clinical practice isometric MVF of quadriceps in hemodialysis patients. Therefore, the belt-stabilized HHD appears as a suitable and a relevant diagnostic tool for the identification of muscle dysfunction in hemodialysis patients.
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http://dx.doi.org/10.1053/j.jrn.2017.01.017DOI Listing
May 2017

Renal graft intolerance syndrome in late graft failure patients: efficacy and safety of embolization as first-line treatment compared to surgical removal.

Transpl Int 2017 May 5;30(5):484-493. Epub 2017 Mar 5.

Department of Nephrology, Dialysis and Transplantation, Montpellier University Hospitals, University of Montpellier Medical School, Montpellier, France.

Although renal graft percutaneous embolization was introduced to avoid the risk associated with graft nephrectomy, there is no universal consensus about its indications and results. In order to evaluate the efficacy of graft embolization in the treatment of graft intolerance syndrome as well as its safety compared to surgical removal with respect to complications and other morbidity measures, We performed a retrospective observational study comparing two groups of patients treated for graft intolerance syndrome: Group 1: patients who had embolization as first-line treatment and Group 2: patients directly treated by surgical removal. 72 patients were included, (32 in Group 1 and 40 in Group 2); the postintervention follow-up continued for 12 months. Patients in Group 1 are older than those in Group 2. Otherwise, the two groups are similar concerning sex, manifestations of graft intolerance syndrome, diabetes and nutritional and functional status. The overall success rate of embolization in complete resolution of graft intolerance syndrome and ultimately avoidance of surgical removal was 84.37%. The surgical removal group had more serious complications, a longer hospital stay and needed more blood transfusions. We conclude that embolization of symptomatic renal grafts has considerable efficacy with less morbidity, and no serious complications compared to the standard surgical graft removal.
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http://dx.doi.org/10.1111/tri.12927DOI Listing
May 2017

[Infectious and neoplasic complications after kidney transplantation].

Nephrol Ther 2016 Nov 24;12(6):468-487. Epub 2016 Sep 24.

Service de néphrologie, dialyse et transplantation, hôpital Lapeyronie, CHU de Montpellier, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France.

Infections and malignancies are the expected complications of immunosuppressive therapy, which non-specifically impairs cellular and humoral immune responses in renal transplant recipients. Infections were usually frequent and severe during the early post-transplant period (first year). Recent diagnostic methods (molecular biology) and availability of new antivirals, antifungal and antibiotic drugs made rapid diagnosis and systematic preventive strategies much easier and this resulted in a significant reduction of infections and infectious death in this population. However, new infectious agents like BK polyomavirus, hepatitis E virus, parvovirus (as well as Chigunkunya, West Nile and others in particular areas) were recently recognized as responsible of aggressive infections in the immunocompromised host. Malignancies are also common after transplantation, due to the intensity and duration of immunosuppression. Skin cancers and lymphoproliferative disorders are the most common and are undoubtedly caused by viral infections, but incidence of non-skin cancers is also increased. After reduction of immunosuppression, treatment is similar to non-transplant patients: Results are usually poor and cancer is now the third cause of death in transplant recipients. Due to their anti-proliferative and anti-tumoral properties, incidence of de novo cancer significantly decreased in patients receiving mTor inhibitors as maintenance immunosuppression; furthermore, in patients already diagnosed with Kaposi sarcoma or recurrent skin cancers, introduction of mTor was associated with stabilisation and/or regression of malignant lesions.
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http://dx.doi.org/10.1016/j.nephro.2016.06.003DOI Listing
November 2016

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

Transplantation 2017 08;101(8):1924-1934

1 Department of Nephrology, Dialysis and Transplantation, Hôpital Lapeyronie, University of Montpellier Medical School, France. 2 Department of Transplantology and Surgery, District Hospital Poznan, Poland. 3 Department of Nephrology, Dialysis and Transplantation, Hôpital Pasteur, CHU de Nice, France. 4 Department of Nephrology, Transplantcenter IKEM, Czech Republic. 5 Department of Nephrology, Transplantation, Dialysis, Hôpital Pellegrin, Université de Bordeaux, France. 6 Department of Transplantation Surgery, Karolinska University Hospital, Sweden. 7 Surgery and Abdominal Transplantation Division, Department of Surgery, Cliniques Universitaires Saint-Luc, Belgium. 8 Department of Urology and Kidney Transplantation of the Surgery Clinic, Tartu University Hospital, Estonia. 9 Department of Infectious Diseases, Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Germany. 10 Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Centre, the Netherlands. 11 Global Medical Affairs, Astellas Pharma Inc., Northbrook, Illinois. 12 Astellas Pharma Europe Ltd, Chertsey, United Kingdom. 13 Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium.

Background: ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens.

Methods: All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival.

Results: The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms.

Conclusions: A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only.
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http://dx.doi.org/10.1097/TP.0000000000001453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542786PMC
August 2017

Evaluation of the New Siemens Tacrolimus Assay on the Dimension EXL Integrated Chemistry System Analyzer: Comparison With an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method.

Ther Drug Monit 2016 12;38(6):808-812

*Laboratoire de Biochimie, CHRU de Montpellier, PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214; †Laboratoire de Biochimie, CHRU de Montpellier, University of Montpellier, INSERM U1061; ‡Service de Néphrologie, Dialyse et Transplantation, CHRU Montpellier, Univ Montpellier 1; and §Service d'Hépato-Gastroentérologie et transplantation, CHRU Montpellier, Univ Montpellier 1, Montpellier, France.

Background: Many patients are maintained at the lower end of the tacrolimus (TAC) reference range (3-7 ng/mL), requiring the use of analytical methods displaying a very low limit of quantification for their follow-up. Therefore, the new Dimension TAC, based on affinity chrome-mediated immunoassay technology, was evaluated on the Dimension EXL Integrated Chemistry System (Siemens Healthcare Diagnostics Inc). The aims of this study were (1) to evaluate the analytical performances with special emphasis on sensibility at low levels of TAC, (2) to compare the results with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method.

Methods: Analytical performance (imprecision, linearity, limit of detection, and limit of quantification) was evaluated. Comparison to UPLC/MS/MS was performed on 106 whole blood samples from 88 transplant recipients using regression analysis and Bland-Altman plot analysis.

Results: Repeatability and within-laboratory coefficients of variation were <6% at mean TAC control levels of 3.7, 11.7, and 19.2 ng/mL. Linearity was confirmed between 1.0 and 22 ng/mL. Passing-Bablok regression analysis of Siemens TAC assay in comparison with UPLC/MS/MS values displayed a slope of 1.09 and an intercept of -0.42. Using Bland-Altman analysis, the mean bias was 0.27 ng/mL with 1.96 SD limits of -2.14 and 2.67 ng/mL.

Conclusions: The new Dimension TAC immunoassay on the EXL analyzer demonstrated reliable and reproducible performances allowing routine monitoring in transplant patients, even at TAC concentrations at the lower end of the therapeutic range.
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http://dx.doi.org/10.1097/FTD.0000000000000331DOI Listing
December 2016

Mortality Prediction after the First Year of Kidney Transplantation: An Observational Study on Two European Cohorts.

PLoS One 2016 6;11(5):e0155278. Epub 2016 May 6.

EA 4275 SPHERE-Biostatistics, Clinical Research and Pharmaco-Epidemiology. Nantes University, Nantes, France.

After the first year post transplantation, prognostic mortality scores in kidney transplant recipients can be useful for personalizing medical management. We developed a new prognostic score based on 5 parameters and computable at 1-year post transplantation. The outcome was the time between the first anniversary of the transplantation and the patient's death with a functioning graft. Afterwards, we appraised the prognostic capacities of this score by estimating time-dependent Receiver Operating Characteristic (ROC) curves from two prospective and multicentric European cohorts: the DIVAT (Données Informatisées et VAlidées en Transplantation) cohort composed of patients transplanted between 2000 and 2012 in 6 French centers; and the STCS (Swiss Transplant Cohort Study) cohort composed of patients transplanted between 2008 and 2012 in 6 Swiss centers. We also compared the results with those of two existing scoring systems: one from Spain (Hernandez et al.) and one from the United States (the Recipient Risk Score, RRS, Baskin-Bey et al.). From the DIVAT validation cohort and for a prognostic time at 10 years, the new prognostic score (AUC = 0.78, 95%CI = [0.69, 0.85]) seemed to present significantly higher prognostic capacities than the scoring system proposed by Hernandez et al. (p = 0.04) and tended to perform better than the initial RRS (p = 0.10). By using the Swiss cohort, the RRS and the the new prognostic score had comparable prognostic capacities at 4 years (AUC = 0.77 and 0.76 respectively, p = 0.31). In addition to the current available scores related to the risk to return in dialysis, we recommend to further study the use of the score we propose or the RRS for a more efficient personalized follow-up of kidney transplant recipients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155278PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859488PMC
July 2017

[Dialysis after graft failure: How to improve survival?].

Nephrol Ther 2016 Apr 10;12 Suppl 1:S89-94. Epub 2016 Mar 10.

Département de néphrologie, dialyse et transplantation, hôpital Lapeyronie, CHU de Montpellier, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France.

Ten to 15 % of transplant recipients will return to dialysis, or require another transplantation within 5years, rising to 23 % by 10years, and failed transplantation is now one of the major indications for starting dialysis, accounting for almost 5 % of incident dialysis patients in the US and 10 % in France. Patients who resume dialysis post-transplantation have usually experienced an extended period of uraemia and long-term immunosuppressive therapy, and exhibit high rates of anaemia and erythropoietin resistance, hypoalbuminaemia and persistent chronic inflammation from the failed graft. These factors may increase mortality risk during the first year of dialysis, as observed in the US, but not in Canada or France. When compared to a control group of transplant-naive patients followed in the same institution in France, patients with transplant failure have a higher rate of usable arteriovenous fistula or graft, a similar rate of non-planned dialysis, and initiate dialysis with a higher glomerular filtration rate. We suggest that patient survival in dialysis after graft loss is influenced by both patient characteristics and quality of care, and this may explain the favourable outcome of this specific dialysis population in France.
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http://dx.doi.org/10.1016/j.nephro.2016.01.007DOI Listing
April 2016

One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial.

Transplantation 2016 Feb;100(2):391-9

1 Service de Néphrologie-Immunologie Clinique, CHU Bretonneau, Tours, France. 2 Université François-Rabelais, Tours, France. 3 Institut de Transplantation, Urologie-Néphrologie (ITUN), CHU, Nantes, France. 4 Université François-Rabelais, Tours, France. 5 Service de Néphrologie, CHU Edouard Herriot, Lyon, France. 6 Service de Néphrologie, CHU Maison Blanche, Reims, France. 7 Service d'Urologie, CHU Pitié Salpêtrière, Paris, France. 8 Service de Néphrologie, CHU Jean Minjoz, Besançon, France. 9 Service de Néphrologie, CHU, Caen, France. 10 Service de Néphrologie, CHU Civil, Strasbourg, France. 11 Service de Néphrologie, CHU, Rouen, France. 12 Service de Néphrologie, CHU, Lille, France. 13 Service de Néphrologie, CHU Henri Mondor, Paris, France. 14 Service de Néphrologie, CHU Necker, Paris, France. 15 Service de Néphrologie-Transplantation-Dialyse, CHU Pellegrin, Bordeaux, France. 16 Service de Néphrologie, CHU, Montpellier, France. 17 Service de Néphrologie, CHU, Dijon, France. 18 Service de Néphrologie, CHU, Lyon, France. 19 Service de Néphrologie, CHU, Marseille, France. 20 Service de Néphrologie, CHU, Limoges, France. 21 Service de Néphrologie-Dialyse-Transplantation, CHU, Angers, France. 22 Service de Néphrologie, CHU, Amiens, France. 23 Service de Néphrologie, CHU, Grenoble, France. 24 Service de Pharmacologie Clinique, CHU Bretonneau, Tours, France. 25 INSERM, CIC 1415, CHU Bretonneau, Tours, France.

Background: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials.

Methods: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12.

Results: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months.

Conclusions: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.
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http://dx.doi.org/10.1097/TP.0000000000000958DOI Listing
February 2016

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study.

BMJ 2015 Jul 31;351:h3557. Epub 2015 Jul 31.

Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris

Objectives: To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥ 60 years or aged 50-59 years with vascular comorbidities) and assess the main determinants of its prognosis.

Design: Prospective, population based cohort study.

Setting: Four French referral centres.

Participants: Consecutive patients who underwent kidney transplantation between January 2004 and January 2011, and were followed up to May 2014. A validation cohort included patients from another four referral centres in France who underwent kidney transplantation between January 2002 and December 2011.

Main Outcome Measures: Long term kidney allograft survival, based on systematic assessment of donor, recipient, and transplant clinical characteristics; preimplantation biopsy; and circulating levels of donor specific anti-HLA (human leucocyte antigen) antibody (DSA) at baseline.

Results: The study included 6891 patients (2763 in the principal cohort, 4128 in the validation cohort). Of 2763 transplantations performed, 916 (33.2%) used ECD kidneys. Overall, patients receiving ECD transplants had lower allograft survival after seven years than patients receiving transplants from standard criteria donors (SCD; 80% v 88%, P<0.001). Patients receiving ECD transplants who presented with circulating DSA at the time of transplantation had worse allograft survival after seven years than patients receiving ECD kidneys without circulating DSA at transplantation (44% v 85%, P < 0.001). After adjusting for donor, recipient, and transplant characteristics, as well as preimplantation biopsy findings and baseline immunological parameters, the main independent determinants of long term allograft loss were identified as allocation of ECDs (hazard ratio 1.84 (95% confidence interval 1.5 to 2.3); P < 0.001), presence of circulating DSA on the day of transplantation (3.00 (2.3 to 3.9); P < 0.001), and longer cold ischaemia time (> 12 h; 1.53 (1.1 to 2.1); P = 0.011). Recipients of ECD kidneys with circulating DSA showed a 5.6-fold increased risk of graft loss compared with all other transplant therapies (P < 0.001). ECD allograft survival at seven years significantly improved with screening and transplantation in the absence of circulating DSA (P < 0.001) and with shorter (<12 h) cold ischaemia time (P=0.030), respectively. This strategy achieved ECD graft survival comparable to that of patients receiving an SCD transplant overall, translating to a 544.6 allograft life years saved during the nine years of study inclusion time.

Conclusions: Circulating DSA and cold ischaemia time are the main independent determinants of outcome from ECD transplantation. Allocation policies to avoid DSA and reduction of cold ischaemia time to increase efficacy could promote wider implement of ECD transplantation in the context of organ shortage and improve its prognosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521904PMC
http://dx.doi.org/10.1136/bmj.h3557DOI Listing
July 2015

PREventing Delayed Graft Function by Driving Immunosuppressive InduCtion Treatment (PREDICT-DGF): study protocol for a randomized controlled trial.

Trials 2015 Jun 23;16:282. Epub 2015 Jun 23.

ITUN and Inserm U1064, Nantes University, 30 Boulevard Jean Monnet, Nantes, 44035, France.

Background: In kidney transplantation, the use of Anti-Thymocyte Globulins (ATG) as induction therapy has been described as a possible treatment for reducing the prevalence of Delayed Graft Function (DGF). ATG possesses pharmaceutical proprieties that could help control the lesions caused by ischemia reperfusion injury. However, other studies have questioned this potential protective effect. We hypothesized that the benefits related to ATG for reducing DGF prevalence may be higher and more consistently recognized if only patients with high DGF risk are considered. We recently proposed a scoring system entitled DGFS (Delayed Graft Function Score) for such stratification of kidney transplant recipients according to their risk of DGF. Using the DGFS calculation, we aim to determine whether a short course of ATG can decrease the incidence of DGF in comparison with Basiliximab in kidney transplant recipients with low immunological risk but high DGF risk.

Methods: We conduct a phase IV, open label, randomized, multicentric and prospective study, to compare ATG in parallel with a control group treated by Basiliximab. The 1:1 randomized allocation of patients between groups is stratified on the clinical center, and on the hypothermic machine-perfusion device. We aimed to include a total of 384 patients to achieve a statistical power at 0.80. The study was initiated at the Nantes University hospital in July 2014, with data collection continuing until April 2018, and publication of the results proposed for 2019.

Discussion: The main expected benefits of this study are i) the reduction of unjustified ATG over-prescriptions associated with serious adverse events, ii) the reduction of chance losses related to ATG under-prescription, iii) the decrease in the incidence of DGF which was described as a risk factor of graft failure and patient death, and iv) the reduction in hospitalization duration and number of post transplantation dialysis sessions, both being associated with reduced medical costs. In conclusion, the current study is innovative by proposing a more efficient and personalized induction therapy.

Trial Registration: The study was registered in the Clinical Trials Registry (# NCT02056938, February 5, 2014), and in the European Clinical Trials Database (EudraCT #2014-000332-42, January 30, 2014).
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http://dx.doi.org/10.1186/s13063-015-0807-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477597PMC
June 2015

Markers of bone remodeling are associated with arterial stiffness in renal transplanted subjects.

J Nephrol 2015 Dec 29;28(6):765-72. Epub 2015 Apr 29.

Service de Médecine Interne, CHRU Montpellier, Univ Montpellier 1, Montpellier, France.

Background: Bone-vessel interaction in chronic renal failure remains poorly understood and could be driven by bone remodeling factors including osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), parathormone and vitamin D. Only few data are available in renal transplantation. The aim of this study was to investigate the relationship between bone remodeling factors and large artery function in renal transplant patients.

Methods: 89 renal transplant patients were enrolled in this cross-sectional study. Carotid to femoral pulse wave velocity (PWV) and central augmentation index (AIx) were determined as an estimation of large artery function. Blood samples were collected for measurement of vascular risk markers. Independent predictors were identified by multivariate linear regression through backward feature selection using Akaike's information criteria.

Results: At multivariate analysis, age (p < 0.001) and systolic arterial pressure (p = 0.003) were significantly associated with PWV but not AIx. In addition, both elevated blood concentrations of 1.25(OH)2 vitamin D (p = 0.013) and OPG (p = 0.047) were still significantly related to high PWV.

Conclusions: These results underline that age and mean arterial pressure are the main determinants of PWV following renal transplantation. Among bone remodeling biomarkers, plasma OPG and active vitamin D were the strongest determinants of arterial stiffness.
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http://dx.doi.org/10.1007/s40620-015-0201-5DOI Listing
December 2015

Arterial stiffness: an independent determinant of adaptive glomerular hyperfiltration after kidney donation.

Am J Physiol Renal Physiol 2015 Mar 7;308(6):F567-71. Epub 2015 Jan 7.

Department of Internal Medicine, Hopital Lapeyronie, Montpellier, France; Université Montpellier 1, Montpellier, France.

After kidney donation, the remaining kidney tends to hyperfiltrate, thus limiting the initial loss of renal function. The potential determinants of this adaptive glomerular hyperfiltration (GHF) and specifically the influence of arterial function are poorly known. In 45 normotensive healthy kidney donors [51 ± 10 yr (mean ± SD), 39 females], glomerular filtration rate (GFR) was measured as the clearance of continuously infused (99m)Tc-DTPA and timed urine collections at baseline, i.e., before donation, and 1 yr after donation. GHF was computed as postdonation GFR minus half of baseline GFR. Arterial function was assessed as baseline carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AIx). After kidney donation, no significant change in blood pressure (BP) was observed, but two subjects developed hypertension. GFR decreased from 107 ± 19 to 73 ± 15 ml·min(-1)·1.73 m(-2), and mean GHF was 20 ± 10 ml·min(-1)·1.73 m(-2). In univariate analysis, GHF was inversely correlated to age (r(2) = 0.24, P = 0.01), baseline PWV (r(2) = 0.23, P = 0.001), and Aix (r(2) = 0.11, P = 0.031). Nevertheless, GHF was not correlated to baseline peripheral or central BP. In multivariate analysis, baseline PWV, but not AIx, remained inversely correlated to GHF, independently of age, baseline mean BP, and GFR (model r(2) = 0.34, P < 0.001). In healthy subjects selected for renal donation, increased arterial stiffness is associated with decreased postdonation compensatory hyperfiltration.
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http://dx.doi.org/10.1152/ajprenal.00524.2014DOI Listing
March 2015

Psoriasis-associated IgA nephropathy under infliximab therapy.

Int J Dermatol 2015 Mar 16;54(3):e79-80. Epub 2014 Dec 16.

Department of Dermatology, Hôpital Saint-Eloi, University of Montpellier I, Montpellier, France.

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http://dx.doi.org/10.1111/ijd.12622DOI Listing
March 2015

[Preventing chronic kidney disease in France: advantages, feasibility and concerns].

Nephrol Ther 2014 Dec 20;10(7):492-9. Epub 2014 Nov 20.

RD-Néphrologie SAS, 104, rue de la Galéra, 34090 Montpellier, France; Service de néphrologie, dialyse et transplantation, hôpital Lapeyronie, 641, avenue du Doyen-Gaston-Giraud, 34295 Montpellier, France; Université Montpellier 1, 641, avenue du Doyen-Gaston-Giraud, 34295 Montpellier, France; Néphrologie, dialyse Saint-Guilhem, Bassin-de-Thau, 40339, 34024 Sète, France. Electronic address:

Chronic kidney disease concerns 10 to 14 % of Western populations, and these people are at increased risk of mortality. Treating those patients who reach end-stage renal disease is socially and financially costly and requires considerable medical efforts. While the number of nephrologists per inhabitant in France seems to be preserved over time, the increasing prevalence of end-stage renal disease and improvement in early referral of chronic kidney disease patients results in increased workload for renal physicians. In order to reduce the consequences of chronic kidney disease at both, individual and societal levels, promoting primary prevention (elimination of risk factors), secondary prevention (early management of patients) or tertiary prevention (optimal treatment of functional disabilities related to chronic kidney disease) seems relevant. Some of these actions could narrow the gap between current medical practices and recommendations or prevent new end-stage renal disease cases with an acceptable cost-effectiveness ratio. New approaches might be necessary to better control the disease and overcome current limitations such as resistance to treatments.
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http://dx.doi.org/10.1016/j.nephro.2014.06.007DOI Listing
December 2014

Prevalence and risk factors of noncontrolled and resistant arterial hypertension in renal transplant recipients.

Transplantation 2015 05;99(5):1016-22

1 Department of Nephrology, Dialysis and Transplantation, Hôpital Lapeyronie, Université de Montpellier, Montpellier, France. 2 Department of Medicine and Hypertension, Hôpital Lapeyronie, Université de Montpellier, Montpellier, France.

Background: Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg.

Methods: We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT.

Results: Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components.

Conclusion: Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation.
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http://dx.doi.org/10.1097/TP.0000000000000467DOI Listing
May 2015

Evaluation of QMS everolimus assay using Indiko analyzer: comparison with an ultra-performance liquid chromatography-tandem mass spectrometry method.

Ther Drug Monit 2015 Apr;37(2):275-8

*Laboratoire de Biochimie; †Service d'Hépato-gastroentérologie et transplantation; and ‡Service de Néphrologie, Dialyse Péritonéale et Transplantation, CHRU Montpellier, Université Montpellier 1, Montpellier, France.

Background: A new particle-enhanced turbidimetric immunoassay, Quantitative Microsphere System (QMS) everolimus, was evaluated using an Indiko analyzer (Thermo Fisher Scientific).

Methods: Analytical performances (imprecision, linearity, limit of detection, and limit of quantification) of this new immunoassay were evaluated. The method was compared with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method and with the previously available Innofluor Certican immunoassay on 120 whole-blood samples from 74 transplant recipients. Passing-Bablok regression and Bland-Altman plot were used for method comparisons.

Results: Within- and between-day coefficients of variation were <10% at mean levels of 4.3, 8.2, and 15.9 ng/mL, respectively. This assay could be used at everolimus concentrations between 1.7 and 20 ng/mL. We obtained a Passing-Bablok regression of y = 0.99 × -0.15 (r = 0.95) when comparing with the UPLC/MS/MS method and of y = 0.81 × -0.09 (r = 0.94) when comparing with Innofluor assay. The mean and limits of agreement (mean ± 1.96 SD) of the difference between QMS everolimus and UPLC/MS/MS were -0.13 (from -2.0 to 1.74) ng/mL and were -1.19 (from -3.39 to 1.01) ng/mL between QMS everolimus and Innofluor.

Conclusions: The QMS everolimus method on Indiko analyzer demonstrated reliable and reproducible performances allowing routine monitoring in transplant patients.
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http://dx.doi.org/10.1097/FTD.0000000000000133DOI Listing
April 2015

Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation.

Kidney Int 2015 Feb 17;87(2):343-9. Epub 2014 Sep 17.

EA 4275 SPHERE-Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France.

Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.
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http://dx.doi.org/10.1038/ki.2014.304DOI Listing
February 2015