Publications by authors named "Valérie Chatelet"

38 Publications

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

Transplantation 2021 Feb 3. Epub 2021 Feb 3.

Department of Transplantation, Nephrology and Clinical Immunology, HCL Hôpital Edouard Herriot, and Université de Lyon, France Department of Hematology, HCL Centre Hospitalier Lyon Sud, and Université de Lyon, France CRCL, INSERM U1052, Pierre-Bénite, France CIRI, INSERM U1111, Lyon, France French PTLD Registry, University Hospital of Strasbourg, France Renal Transplantation Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital, Paris, France Department of Nephrology, AP-HM Hôpital de la Conception, Marseille, France Department of Nephrology and Transplantation, Hôpital Hôtel Dieu, Nantes, France Transplant Unit, Nephrology Department, University Hospital, Reims, France Transplant Unit, Department of Nephrology, University Hospital, Rennes, France Department of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, France Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicetre, France Transplant Unit, Nephrology Department, University Hospital, Lille, France Transplant Unit, Nephrology Department, Besançon University Hospital, Besançon, France Transplant Unit, Nephrology Department, University Hospital, Amiens, France Nephrology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France Department of Nephrology, Dupuytren Hospital, Limoges, France Department of Urology, Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris Department of Nephrology and Renal Transplantation, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Henri-Mondor, Créteil, France Nephrology Department, CHU de Caen, Caen, France Transplant Unit, Nephrology Department, Dijon University Hospital, Dijon, France Department of Nephrology, University Hospital, Grenoble, France Department of Nephrology, Dialysis and Transplantation, Lapeyronie University Hospital, Montpellier, France Transplant Unit, Nephrology Department, Nancy University Hospital, Nancy, France epartment of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France Urgences Néphrologiques et Transplantation Rénale, Assistance Publique-Hôpitaux de Paris (AP-HP), Tenon Hospital, Paris, France Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris (AP-HP), Saint Louis Hospital, Paris, France Department of Nephrology Dialysis and Kidney Transplantation, CHU de Poitiers, Poitiers, France Nephrology, Dialysis and Renal Transplantation Department, Hôpital Nord, CHU de Saint-Etienne, France Nephrology, Dialysis and Renal Transplantation Department, Centre Hospitalier Régional Universitaire Tours, France INSERM U955, Université Paris-Est, and Department of pathology, APHP Hôpital Henri Mondor, Créteil, France Department of Hematology, APHP Hôpital Pitié-Salpétrière, Paris, France. Etablissement Français du Sang, Lyon, France Department of Nephrology and Transplantation, University Hospital of Strasbourg, France.

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

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

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

Conclusions: This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.
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http://dx.doi.org/10.1097/TP.0000000000003568DOI Listing
February 2021

Eculizumab discontinuation in children and adults with atypical haemolytic uremic syndrome: a prospective multicentric study.

Blood 2020 Dec 3. Epub 2020 Dec 3.

Assistance Publique - Hôpitaux de Paris, paris, France.

The optimal duration of eculizumab treatment in patients with atypical haemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicentric open-label study in order to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean duration of treatment, 16.5 months). Twenty-eight (51%) patients had complement gene rare variants, mostly in MCP (n= 12, 22%), CFH (n= 6, 11%) and CFI (n=6, 10%) genes. At eculizumab discontinuation, 17 (30%) and 4 (7%) patients had chronic kidney disease stage 3 and 4, respectively. During follow-up, 13 (23%) patients (6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female gender and the presence of a rare complement gene variant were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during previous episodes of acute aHUS was not. In addition, an increased soluble C5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers of complement gene rare variants, in log rank test and in multivariable analysis. Among the 13 relapsing patients, who were all restarted on eculizumab, 11 regained their baseline renal function and two had a worsening of their pre-existing chronic kidney disease, including one patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. Trail registration number: NCT02574403.
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http://dx.doi.org/10.1182/blood.2020009280DOI Listing
December 2020

Paternity in male kidney transplant recipients: a French national survey, the PATeRNAL study.

BMC Nephrol 2020 11 16;21(1):483. Epub 2020 Nov 16.

Centre Universitaire des Maladies Rénales, CHU de Caen, Avenue de la côte de Nacre, 14033, Caen, Cedex 9, France.

Background: There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males.

Methods: This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes.

Results: The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15-20]). There were 37 (9%, 95% CI [7-12]) spontaneous abortions, 12 (3%, 95% CI [2-5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1-1]) still births, and 13 (4%, 95% CI [2-6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents.

Conclusions: This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.
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http://dx.doi.org/10.1186/s12882-020-02115-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667842PMC
November 2020

Kidney transplantation improves the clinical outcomes of Acute Intermittent Porphyria.

Mol Genet Metab 2020 Sep - Oct;131(1-2):259-266. Epub 2020 Sep 2.

Nephrology Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris University, France; Clinical Chemistry Department, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, France. Electronic address:

Background: Acute Intermittent Porphyria (AIP) is a rare inherited autosomal dominant disorder of heme biosynthesis. Porphyria-associated kidney disease occurs in more than 50% of the patients with AIP, and end stage renal disease (ESRD) can be a devastating complication for AIP patients. The outcomes of AIP patients after kidney transplantation are poorly known.

Methods: We examined the outcomes of 11 individuals with AIP, identified as kidney transplant recipients in the French Porphyria Center Registry.

Results: AIP had been diagnosed on average 19 years before the diagnosis of ESRD except for one patient in whom the diagnosis of AIP had been made 5 years after the initiation of dialysis. Median follow-up after transplantation was 9 years. A patient died 2 months after transplantation from a cardiac arrest and a patient who received a donation after cardiac death experienced a primary non-function. No rejection episode and no noticeable adverse event occurred after transplantation. Serum creatinine was on average 117 μmol/l, and proteinuria <0.5 g/l in all patients at last follow up. All usually prescribed drugs after transplantation are authorized except for trimethoprim/sulfamethoxazole. Critically, acute porphyria attacks almost disappeared after kidney transplantation, and skin lesions resolved in all patients.

Conclusion: Kidney transplantation is the treatment of choice for AIP patients with ESRD and dramatically reduces the disease activity.
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http://dx.doi.org/10.1016/j.ymgme.2020.08.004DOI Listing
September 2020

[What do we know about these dialysed patients who are not on the waiting list?]

Nephrol Ther 2020 May 11;16(3):137-138. Epub 2020 May 11.

Centre universitaire des maladies rénales, CHU de Caen, avenue de la Côte-de-Nacre, CS 30001, 14033 Caen cedex 9, France; U1086 Inserm, « ANTICIPE », centre de lutte contre le cancer François-Baclesse, 3, avenue du Général-Harris, BP 5026, 14076 Caen cedex 05, France.

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http://dx.doi.org/10.1016/j.nephro.2020.02.011DOI Listing
May 2020

An extension of the RITUX-ERAH study, multicenter randomized clinical trial comparing rituximab to placebo in acute antibody-mediated rejection after renal transplantation.

Transpl Int 2020 Jul 5;33(7):786-795. Epub 2020 May 5.

Department of Nephrology, Hypertension, Dialysis and Kidney Transplantation, University hospital of Tours, Tours, France.

The treatment of active antibody-mediated rejection (ABMR) is still a matter of debate, the place of rituximab remaining controversial. The French multicenter double-blind RITUX-ERAH study included 38 patients with ABMR in the first year of renal transplantation. All patients received plasma exchanges, intravenous immunoglobulins, and corticosteroids and were randomly assigned rituximab or placebo infusion at day 5. Additional rituximab infusions were allowed. In the intention-to-treat analysis, 12-month graft survival and renal function were not different between the rituximab and placebo groups. Long-term data are needed to conclude. Evaluation of the 7-year outcomes of the RITUX-ERAH study patients according to the rituximab or placebo treatment received. Eleven patients received placebo and 27 at least one infusion of rituximab. Seven years after ABMR, death-censored kidney allograft survival and renal function were not different between the groups. The evolution of anti-HLA sensitization was similar. There was no statistically significant difference in the incidence of infectious or neoplastic complications, but to be noted, seven cancers developed in six patients treated with rituximab (mean period of 44 months post-ABMR). In this cohort, there was no benefit 7 years after ABMR of rituximab in addition to plasma exchanges, intravenous immunoglobulins, and steroids.
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http://dx.doi.org/10.1111/tri.13613DOI Listing
July 2020

[Ericksonian hypnosis and mindfulness meditation: Towards a behavioral medicine in nephrology].

Nephrol Ther 2020 Mar 9;16(2):93-96. Epub 2020 Jan 9.

Centre universitaire des maladies rénales, CHU de Caen, avenue Côte de Nacre CS 30001, 14033 Caen cedex 9, France; U1086 Inserm, "ANTICIPE", centre de lutte contre le cancer François-Baclesse, 3, avenue du Général-Harris, BP 5026 14076 Caen cedex 05, France.

The utilization of behavioral medicine, like Ericksonian hypnosis and mindfulness meditation, in the patient care is increasing. Psychological disorders associated with chronic renal failure are similar to the post-traumatic stress disorder and need a continuous personnel adjustment. Preventing depression, managing stress, pain and emotions, like anger, guiltiness and shame, is of importance in individual who suffer of chronic kidney disease, but also in their family caregivers and in health-care workers. The objective of this report is to describe how Ericksonian hypnosis, mindfulness meditation and compassion meditation could support chronic kidney disease patients, their caregivers and the health-care professional.
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http://dx.doi.org/10.1016/j.nephro.2019.08.002DOI Listing
March 2020

Is self-care dialysis associated with social deprivation in a universal health care system? A cohort study with data from the Renal Epidemiology and Information Network Registry.

Nephrol Dial Transplant 2020 05;35(5):861-869

Centre Universitaire des maladies rénales, CHU de Caen, Caen, France.

Background: Socioeconomic status is associated with dialysis modality in developed countries. The main objective of this study was to investigate whether social deprivation, estimated by the European Deprivation Index (EDI), was associated with self-care dialysis in France.

Methods: The EDI was calculated for patients who started dialysis in 2017. The event of interest was self-care dialysis 3 months after dialysis initiation [self-care peritoneal dialysis (PD) or satellite haemodialysis (HD)]. A logistic model was used for the statistical analysis, and a counterfactual approach was used for the causal mediation analysis.

Results: Among the 9588 patients included, 2894 (30%) were in the most deprived quintile of the EDI. A total of 1402 patients were treated with self-care dialysis. In the multivariable analysis with the EDI in quintiles, there was no association between social deprivation and self-care dialysis. Compared with the other EDI quintiles, patients from Quintile 5 (most deprived quintile) were less likely to be on self-care dialysis (odds ratio 0.81, 95% confidence interval 0.71-0.93). Age, sex, emergency start, cardiovascular disease, chronic respiratory disease, cancer, severe disability, serum albumin and registration on the waiting list were associated with self-care dialysis. The EDI was not associated with self-care dialysis in either the HD or in the PD subgroups.

Conclusions: In France, social deprivation estimated by the EDI is associated with self-care dialysis in end-stage renal disease patients undergoing replacement therapy.
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http://dx.doi.org/10.1093/ndt/gfz245DOI Listing
May 2020

Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome.

J Am Soc Nephrol 2019 12 1;30(12):2449-2463. Epub 2019 Oct 1.

French Study Group of Atypical Hemolytic Uremic Syndrome, France.

Background: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.

Methods: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (=397) between 2007 and 2016.

Results: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.

Conclusions: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
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http://dx.doi.org/10.1681/ASN.2019040331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900783PMC
December 2019

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Blood 2019 12;134(24):2209-2217

Service d'Hématologie, AP-HP.6, Paris, France; and.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.
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http://dx.doi.org/10.1182/blood.2019000748DOI Listing
December 2019

Social deprivation is associated with poor kidney transplantation outcome in children.

Kidney Int 2019 09 28;96(3):769-776. Epub 2019 May 28.

University of Bordeaux, ISPED, Centre INSERM U1219-Bordeaux Population Health Research, Bordeaux, France; INSERM, Clinical Investigation Center-Clinical Epidemiology-CIC-1401, Bordeaux, France; Pediatric Nephrology Unit, Pellegrin-Enfants Hospital, Bordeaux University Hospital, Centre de Référence Maladies rénales rares Sorare, Bordeaux, France. Electronic address:

Socioeconomic status is an important determinant of health. Its impact on kidney transplantation outcome has been studied among adults but data in children are scarce, especially in Europe. Here, we investigate the association between the level of social deprivation (determined by the continuous score European Deprivation Index) and graft failure risk in pediatric kidney transplant recipients. All patients listed under 18 years of age who received a first kidney transplant between 2002 and 2014 in France were included. Of 1050 kidney transplant recipients (males 59%, median age at transplantation 13.2 years, preemptive transplantation 23%), 211 graft failures occurred within a median followup of 5.9 years. Thirty-seven percent of these patients belong to the most deprived quintile, suggesting that deprivation is more frequent in pediatric patients with end-stage kidney disease (ESKD) than in the general population. Five- and ten-year graft survival were 85% and 69%, respectively, in the most deprived quintile vs. 90% and 83%, respectively, in the least deprived quintile. At any time after transplantation, patients in the most deprived quintile had almost a two-fold higher hazard of graft failure compared with the least deprived quintile, after adjustment for age at renal replacement therapy, duration of dialysis, primary kidney disease, and rural/urban living environment (hazard ratio 1.99; 95% confidence interval 1.20-3.28). The hazard of graft failure did not differ significantly between girls and boys. Thus, our findings suggest a lower socioeconomic status is independently associated with poor graft outcome in pediatric kidney transplantation.
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http://dx.doi.org/10.1016/j.kint.2019.05.011DOI Listing
September 2019

Transplant center characteristics associated with living-donor kidney transplantation: a cohort study with a hierarchical modeling approach.

Transpl Int 2019 Aug 2;32(8):865-875. Epub 2019 Apr 2.

Service de Néphrologie et Transplantation, Hôpital Civil, Strasbourg, France.

Transplant center organization, that is a modifiable factor, may affect the access to living-donor kidney transplantation (LDKT). The objective of this study was to identify the center characteristics associated with LDKT using a hierarchical analysis. This was a retrospective multicenter observational study of 8701 patients who received a first renal graft between 2010 and 2014 in 32 transplantation centers of France. Hierarchical modeling was used to estimate the center effect and organization associated with LDKT. Among 8507 patients, 1225 (12%) were transplanted with a LD kidney. There was a transplant center effect on the proportion of LDKT. After adjustment for patient and center characteristics, the random effect variance decreased by 47%. Patients transplanted at a center with more than four nephrologists [1.81 (95% CI: 1.10-2.95)] and more than 1.5 nurse transplant coordinators [1.98 (95% CI: 1.26-3.13)] were more likely to be transplanted with a LD kidney. ABO-incompatible program was associated with LDKT [2.23 (95% CI: 1.22-4.06)]. There was a transplant center effect on the proportion of LDKT that could be decreased by modifiable center characteristics. Our study suggests the importance of the transplant team organization on the LDKT utilization.
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http://dx.doi.org/10.1111/tri.13429DOI Listing
August 2019

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy.

Kidney Int Rep 2018 Sep 8;3(5):1153-1162. Epub 2018 Jun 8.

Nephrology Department, Rouen University Hospital, Rouen, France.

Introduction: Cobalamin C (cblC) deficiency is the most common inborn error of vitamin B metabolism. Renal failure attributed to thrombotic microangiopathy (TMA) has occasionally been described in the late-onset presentation of cblC deficiency, but kidney lesions associated with cblC deficiency remain poorly defined. This study aims to describe the characteristics of kidney disease in cblC deficiency, and to provide a comparative histological analysis with cblC-independent renal TMA.

Methods: We performed a multicenter retrospective study including 7 patients with cblC deficiency and 16 matched controls with cblC-independent TMA. The patients included were aged 6 to 26 years at the time of the first manifestations. All patients presented with acute renal failure, proteinuria, and hemolysis; 5 patients required dialysis.

Results: The histological study revealed arteriolar and glomerular TMA in all patients. After comparison with the cblC-independent TMA control group, a vacuolated aspect of the glomerular basement membrane and the intensity of glomerular capillary wall IgM deposits were more present in cblC deficiency patients than in controls. Six patients were treated with hydroxycobalamin. All of them improved, with disappearance of hemolysis, and 3 of the 4 patients requiring renal replacement therapy were weaned off dialysis.

Conclusion: This study provides a precise description of kidney pathology in cblC deficiency. Due to major therapeutic implications, we suggest that patients with renal TMA be screened for cblC deficiency regardless of age, particularly when the kidney biopsy provides evidence of long-lasting TMA, including a vacuolated aspect of the glomerular basement membrane and glomerular capillary wall IgM deposition.
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http://dx.doi.org/10.1016/j.ekir.2018.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127440PMC
September 2018

Sirolimus for Secondary Prevention of Skin Cancer in Kidney Transplant Recipients: 5-Year Results.

J Clin Oncol 2018 09 17;36(25):2612-2620. Epub 2018 Jul 17.

Jacques Dantal and Anabelle Brocard, Nantes University Hospital, Nantes; Emmanuel Morelon, Claire Pouteil-Noble, Jean Kanitakis, and Sylvie Euvrard, Hospices Civils de Lyon, Edouard Herriot Hospital Group; Adeline Roux and Evelyne Decullier, Hospices Civils de Lyon, Unité de Recherche Clinique, Lyon; Lionel Rostaing and Nassim Kamar, Toulouse University Hospital, Toulouse; Valérie Chatelet and Anne Dompmartin, University Hospital of Caen, Caen; Michèle Kessler, University Hospital of Nancy, Vandœuvre-lès-Nancy, France; Eric Goffin and Isabelle Tromme, St Luc University Hospital, Woluwe-Saint-Lambert; Nilufer Broeders and Véronique del Marmol, Université Libre de Bruxelles, Bruxelles, Belgium; and Andreas Serra and Günther F.L. Hofbauer, Zürich University Hospital, Zürich, Switzerland.

Purpose Transplant recipients who develop cutaneous squamous cell carcinomas are at high risk for multiple subsequent skin cancers. Sirolimus has been shown to reduce the occurrence of secondary skin cancers, but no study included a follow-up exceeding 2 years. We extended at 5 years the TUMORAPA randomized trial of sirolimus-based immunosuppressive regimen versus calcineurin inhibitor-based immunosuppression. Methods Kidney transplant recipients receiving calcineurin inhibitors who had at least one cutaneous squamous cell carcinoma were randomly assigned to receive sirolimus as a substitute for calcineurin inhibitors (n = 64) or to maintain their initial treatment (n = 56). The primary end point was survival free of squamous cell carcinoma at 5 years. Secondary end points included the occurrence of other skin cancers, renal function, patient and graft survival, and treatment tolerance. Results Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group than in the calcineurin inhibitor group ( P = .007). In the sirolimus group, the number of patients with new skin cancers was significantly lower compared with the calcineurin inhibitor group: 22% versus 59% for squamous cell carcinomas ( P < .001), 34% versus 66% for other skin cancers ( P < .001), and 20% versus 37.5% for basal cell carcinomas ( P < .05). Kidney graft function, patients, and graft survival were similar in both groups. In the sirolimus group, the mean number of serious adverse effects per patient decreased from 1.16 during the first 2 years, to 0.83 between years 2 and 5. Conclusion In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and sirolimus tolerance was satisfactory.
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http://dx.doi.org/10.1200/JCO.2017.76.6691DOI Listing
September 2018

Renal transplantation outcome and social deprivation in the French healthcare system: a cohort study using the European Deprivation Index.

Transpl Int 2018 10 16;31(10):1089-1098. Epub 2018 Apr 16.

Centre Universitaire des Maladies Rénales, CHU de Caen, Caen Cedex 9, France.

The study objective was to estimate the effect of social deprivation estimated by the European Deprivation Index (EDI) on the risk of death and graft failure on renal transplantation in France. EDI was calculated for 8701 of 9205 patients receiving a first renal transplantation between 2010 and 2014. Patients were separated in EDI quintiles of the general population. A Cox model (cs-HR: cause-specific hazard ratio of death or graft failure) and a Fine and Gray model (sd-HR: subdistribution hazard ratio of death and graft failure) were used for the analysis. The 5th quintile group (most deprived) accounted for 32% of patients [2818 of 8701]. In the multivariate analysis, compared with quintile 1, the risk of death was higher for the 5 quintile group in the complete cohort [cs-HR: 1.31, 95% CI: (1.01-1.70), sd-HR: 1.29, 95% CI: (1.00-1.68)], in the deceased donor group [cs-HR: 1.31, 95% CI: (1.00-1.71), sd-HR: 1.30, 95% CI: (1.00-1.70)] but not in living donor transplant patients. There was no association between the EDI groups and the risk of transplant failure. Social deprivation estimated by the EDI is associated with an increased risk of death in transplantation in France but not with the chance of allograft loss.
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http://dx.doi.org/10.1111/tri.13161DOI Listing
October 2018

Eculizumab reversed severe distal ischemic syndrome and glomerulonephritis with isolated C3 deposits associated with anti-factor H autoantibodies: a case report.

Clin Rheumatol 2018 Apr 7;37(4):1119-1122. Epub 2018 Mar 7.

Department of Internal Medicine and Clinical Immunology, CHU Côte de Nacre-Université Basse Normandie, Avenue de la Côte de Nacre, 14000, Caen, France.

B-cell clones can produce a monoclonal immunoglobulin, which may be responsible for visceral involvements. Kidney involvement is frequent, affecting 20 to 50% of patients with multiple myeloma. One mechanism underlying this involvement is a dysregulation of the complement alternative pathway, leading to C3 glomerulopathies. We report a patient who had a multiple myeloma, C3 glomerulopathy related to factor H autoantibody, and digital ischemia, who was treated successfully with eculizumab, an anti-complement therapy, without any relapse in 2 years of follow-up.
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http://dx.doi.org/10.1007/s10067-018-4058-6DOI Listing
April 2018

[Socioeconomic inequalities and kidney transplantation].

Nephrol Ther 2018 Apr 1;14(2):81-84. Epub 2017 Dec 1.

Service de néphrologie, CHU Pontchaillou, 2, rue Henri-le-Guilloux, 35000 Rennes, France.

Studies at the population level must take into account the effect of social insecurity and socioeconomic inequalities on the patient outcomes. Socioeconomic inequalities depend on many determinants that are socially determined. In renal transplantation, these social determinants are not registered in the databases. The European Deprivation Index (EDI) is a composite index of social vulnerability with a French version. The EDI is an ecological measure of deprivation including the individual perception of basic needs for daily life that is called "subjective poverty". The Townsend index, Carstairs index and the Index of Multiple Deprivation are other ecological index available. It has been demonstrated in the United States that socioeconomic indicators of deprivation were associated with both the access to the waiting list for renal transplantation and transplantation failure. In France, socioeconomic deprivation may also affect the access to the waiting list and outcome of transplantation. This article is a review about deprivation and renal transplantation.
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http://dx.doi.org/10.1016/j.nephro.2017.04.003DOI Listing
April 2018

Prognostic Value of the Persistence of C1q-Binding Anti-HLA Antibodies in Acute Antibody-Mediated Rejection in Kidney Transplantation.

Transplantation 2018 04;102(4):688-698

Department of Nephrology and Kidney Transplantation, University Hospital of Tours, Tours, France.

Background: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs helps in better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown.

Methods: We included patients from the French multicenter RITUX ERAH study diagnosed with acute ABMR within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment.

Results: Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (P = 0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (P = 0.006), greater C4d score deposition score at 6 months after ABMR (P = 0.008), and graft loss 5 years after ABMR (P = 0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect.

Conclusion: The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification.
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http://dx.doi.org/10.1097/TP.0000000000002002DOI Listing
April 2018

[Outcome of living kidney donors for transplantation].

Nephrol Ther 2017 Nov 12;13(6):448-459. Epub 2017 Oct 12.

Service de néphrologie, dialyse et transplantation, CUMR, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France; Normandie université, Unicaen, UFR de médecine, 2 rue des rochambelles, 14032 Caen cedex, France.

Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up.
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http://dx.doi.org/10.1016/j.nephro.2017.02.011DOI Listing
November 2017

Kidney transplantation in patients with systemic sclerosis: a nationwide multicentre study.

Transpl Int 2017 Mar;30(3):256-265

Nephrology Dialysis Transplantation, Centre Hospitalier Universitaire de Rouen, Rouen, Haute-Normandie, France.

Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period. Initial kidney disease was scleroderma renal crisis in 76.4%. Extrarenal involvement of SS was generally stable, except cardiac and gastrointestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases, respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3 and 5 years post-transplant, respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in three cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extrarenal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation.
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http://dx.doi.org/10.1111/tri.12923DOI Listing
March 2017

Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

Clin J Am Soc Nephrol 2017 01 31;12(1):50-59. Epub 2016 Oct 31.

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

Background And Objectives: The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome.

Design, Setting, Participants & Measurements: Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse.

Results: Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (<7 days) hematologic remission and a return of serum creatinine to baseline level in a median time of 26 days. At last follow-up, renal function remained unchanged in nonrelapsing and relapsing patients compared with baseline values before eculizumab discontinuation.

Conclusions: Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients.
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http://dx.doi.org/10.2215/CJN.06440616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220663PMC
January 2017

Successful renal retransplantation after graft loss from BK polyomavirus infection in a human immunodeficiency virus-positive patient.

Transpl Infect Dis 2016 Dec 10;18(6):946-949. Epub 2016 Nov 10.

Department of Nephrology, CHU de Caen, Caen, France.

We report the case of a human immunodeficiency virus-seropositive patient whose initial kidney transplant failed because of BK polyomavirus-induced nephropathy, and who underwent a second transplantation 3 years later. BK viruria was detected 1 day after transplantation. After 1 month, BK viremia developed along with a donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor-specific antibody permanently disappeared, with stable renal function.
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http://dx.doi.org/10.1111/tid.12615DOI Listing
December 2016

[BK virus infections in kidney transplantation].

Nephrol Ther 2016 Apr 28;12(2):76-85. Epub 2016 Jan 28.

Service de néphrologie, dialyse et transplantation, CUMR, CHU de Caen, avenue de la Côte-de-Nâcre, 14033 Caen cedex, France. Electronic address:

BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.
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http://dx.doi.org/10.1016/j.nephro.2015.11.003DOI Listing
April 2016

[PRETAGREF study: Prevalence of tobacco use and factors associated with smoking cessation in kidney transplant recipients].

Nephrol Ther 2016 Feb 23;12(1):48-55. Epub 2015 Nov 23.

Service de néphrologie, CHU Clémenceau, avenue de la Côte-de-Nacre, 14033 Caen cedex, France.

Introduction: Tobacco use increases the risk of mortality, cancers and cardiovascular diseases in transplanted patients. Transplanted patients are encouraged to quit tobacco use before and after renal transplantation. This study was carried out to evaluate the prevalence of tobacco consumption in transplanted patients in one French region. This survey was also conducted to identify factors associated with failure in smoking cessation.

Materials And Method: A questionnaire was sent by mail to transplanted patients followed in our center between the 1/01/95 and the 31/12/10. A second mail was sent to increase the response rate.

Results: During the study period, 544 questionnaires were sent to kidney transplant recipients. Among these 544 patients, there were 362 responders. Of these 362 patients, 121 patients (33.4%) were past smokers, and 21 (5.8%) were active smokers. Among the smokers, 20% were exposed to second-hand smoke, 48% had criteria for tobacco moderate to high dependency, and 13.4% were addicted to alcohol. In the multivariate analysis, exposure to second-hand smoke and living alone at home were associated with failure in smoking cessation.

Conclusion: This study shows that the prevalence of tobacco use is not high in transplanted patients. Only 6% of our patients report tobacco use at the study time. Environmental factors are associated with failure in tobacco cessation. Living alone and exposure to second-hand smoke are associated with smoking. Therefore, in transplantation centers, programs devoted to tobacco cessation should be implemented and should take care of patients' lifestyle.
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http://dx.doi.org/10.1016/j.nephro.2015.08.001DOI Listing
February 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

Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency.

Lancet 2015 Sep;386(9997):1011-2

Nephrology Department, Rouen University Hospital, Rouen, France; INSERM U1096, Rouen University Medical School, Rouen, France; IRIB, Institute for Research and Innovation in Biomedicine, Rouen, France.

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http://dx.doi.org/10.1016/S0140-6736(15)00076-8DOI Listing
September 2015

Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases.

Am J Kidney Dis 2014 Jan 8;63(1):40-8. Epub 2013 Sep 8.

Department of Immunology, Assistance Publique-Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris, France.

Background: Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys.

Study Design: A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 μmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included.

Setting & Participants: 19 patients were identified through a query sent to all French nephrology centers.

Outcomes & Measurements: Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy.

Results: All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls.

Limitations: Retrospective study and use of historical controls.

Conclusions: Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.
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http://dx.doi.org/10.1053/j.ajkd.2013.07.011DOI Listing
January 2014

Sirolimus and secondary skin-cancer prevention in kidney transplantation.

N Engl J Med 2012 Jul;367(4):329-39

Department of Dermatology, Hospices Civils de Lyon, Edouard Herriot Hospital Group, Lyon, France.

Background: Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed.

Methods: In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus.

Results: Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups.

Conclusions: Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
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http://dx.doi.org/10.1056/NEJMoa1204166DOI Listing
July 2012

Renal resistive index as a new independent risk factor for new-onset diabetes mellitus after kidney transplantation.

Transpl Int 2012 Apr 24;25(4):464-70. Epub 2012 Feb 24.

Service de Néphrologie-Immunologie Clinique, Hôpital Bretonneau, CHRU Tours, Tours, France.

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 0≤0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT.
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http://dx.doi.org/10.1111/j.1432-2277.2012.01445.xDOI Listing
April 2012

Hydration status of patients with end-stage renal disease after kidney transplantation.

Clin Transplant 2011 Nov-Dec;25(6):E656-63. Epub 2011 Aug 24.

Nephrology Department, CHU Clemenceau, Caen, France.

Background: This study was carried out to estimate the modification of hydration status within the first three months of renal transplantation.

Subjects And Methods: Fifty patients who underwent a first kidney allograft were prospectively followed for three months after renal transplantation to assess hydration status by bioimpedance spectroscopy.

Results: Two hours before the transplant procedure, 10/42 (23.8%) patients were overhydrated. Two days after surgery, 32/40 (80.0%) patients were overhydrated and at three months, 14/27 (51.9%) patients remained fluid-overloaded. Peritoneal dialysis (PD) patients had a lower hydration status (-0.60 L) than hemodialysis (HD) patients (0.70 L; p < 0.05) and better residual diuresis (41.7 vs. 8.3 mL/h for HD patients, p < 0.01). Compared with patients who had a delayed graft function (DGF) or a slow graft function (SGF), the immediate graft function (IGF) group had a better hydration status before transplantation (p = 0.031). At three months, 12/14 of the overhydrated patients had a creatinine clearance between 30 and 60 mL/min/1.73 m(2) .

Conclusion: Patients receiving a first kidney transplant frequently have a hydration disorder. Transplantation is associated with increased hydration status, which seems to persist if DGF or SGF occurs.
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http://dx.doi.org/10.1111/j.1399-0012.2011.01496.xDOI Listing
May 2012