Publications by authors named "Dany Anglicheau"

138 Publications

Poor Anti-SARS-CoV-2 Humoral and T-cell Responses After 2 Injections of mRNA Vaccine in Kidney Transplant Recipients Treated with Belatacept.

Transplantation 2021 Apr 8. Epub 2021 Apr 8.

Department of Nephrology and Kidney Transplantation, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Université de Paris, Paris, France Immunology Laboratory, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France CNRS UMR8253, INSERM UMR1151, Institut Necker-Enfants Malades, Paris, France. INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, Toulouse, France. Toulouse III Paul Sabatier University, Toulouse, France. Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, Toulouse, France. Virology Laboratory, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Virology Laboratory, Toulouse Purpan University Hospital, Toulouse, France. Department of infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1097/TP.0000000000003784DOI Listing
April 2021

Belatacept as maintenance therapy in kidney transplant recipients with ANCA-associated vasculitis.

Clin Exp Rheumatol 2021 Mar 18. Epub 2021 Mar 18.

University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.

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March 2021

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

Impact of Covid-19 on kidney transplant and waiting list patients: Lessons from the first wave of the pandemic.

Nephrol Ther 2021 Jan 8. Epub 2021 Jan 8.

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

Background: The first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates.

Methods: French kidney patients were contacted to answer an online electronic survey at the end of the lockdown.

Results: At the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P<0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P=0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P<0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do.

Conclusions: During the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients' needs.
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http://dx.doi.org/10.1016/j.nephro.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791308PMC
January 2021

Ig-responsive relapsing inflammatory syndrome following COVID-19 in a kidney transplant recipient.

Kidney Int 2021 03 22;99(3):767-768. Epub 2021 Jan 22.

Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France.

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http://dx.doi.org/10.1016/j.kint.2020.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826029PMC
March 2021

Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study.

Am J Transplant 2021 Jan 29. Epub 2021 Jan 29.

Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.
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http://dx.doi.org/10.1111/ajt.16504DOI Listing
January 2021

Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation.

Front Immunol 2020 10;11:604353. Epub 2020 Dec 10.

Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08-2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.
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http://dx.doi.org/10.3389/fimmu.2020.604353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759001PMC
December 2020

Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept.

Am J Transplant 2020 Dec 6. Epub 2020 Dec 6.

Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.
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http://dx.doi.org/10.1111/ajt.16430DOI Listing
December 2020

MicroRNAs: small molecules, big effects.

Curr Opin Organ Transplant 2021 Feb;26(1):10-16

Université de Paris, Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151.

Purpose Of Review: In kidney transplantation, microRNAs (miRNAs) have been extensively studied over the past decade, and panels of differentially expressed miRNAs have been identified from various body fluids/tissues, including blood, plasma, urine, or allograft biopsies, and in various conditions, such as acute T-cell-mediated and antibody-mediated rejections, chronic allograft rejection, interstitial fibrosis and tubular atrophy, acute tubular necrosis or BKV nephropathy.

Recent Findings: This review outlines our current knowledge regarding the complexity of miRNA regulation in fine-tuning expression of two-thirds of the human genome and the potential of miRNAs as biomarkers, based on an increasing number of case--control studies with, however, no evidence of short-term clinical development. Instead, a progressive change in study objectives is reported, with the most recent literature using miRNA-targeted genes as entry points for studying disease pathways.

Summary: Our nascent understanding of their presumed roles in alloimmunity suggests that miRNAs are key regulators in many allograft injuries. Future directions should investigate how the integration of miRNAs with other layers of molecular data, such as genomic, transcriptomic, or proteomic data, could help to characterize the cellular interactions involved in allograft rejection and whether miRNA-based therapy could be of relevance for transplant medicine.
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http://dx.doi.org/10.1097/MOT.0000000000000835DOI Listing
February 2021

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

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

Department of Infectious Diseases, Strasbourg University Hospital, Strasbourg, France.

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.
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http://dx.doi.org/10.1111/ajt.16424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753418PMC
March 2021

COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities.

Am J Transplant 2021 03 4;21(3):1285-1294. Epub 2021 Jan 4.

Départment de Néphrologie et transplantation rénale, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.

Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.
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http://dx.doi.org/10.1111/ajt.16416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753406PMC
March 2021

IMPact of the COVID-19 epidemic on the moRTAlity of kidney transplant recipients and candidates in a French Nationwide registry sTudy (IMPORTANT).

Kidney Int 2020 12 31;98(6):1568-1577. Epub 2020 Oct 31.

Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France.

End stage kidney disease increase the risk of COVID-19 related death but how the kidney replacement strategy should be adapted during the pandemic is unknown. Chronic hemodialysis makes social distancing difficult to achieve. Alternatively, kidney transplantation could increase the severity of COVID-19 due to therapeutic immunosuppression and contribute to saturation of intensive care units. For these reasons, kidney transplantation was suspended in France during the first epidemic wave. Here, we retrospectively evaluated this strategy by comparing the overall and COVID-19 related mortality in kidney transplant recipients and candidates over the last three years. Cross-interrogation of two national registries for the period 1 March and 1 June 2020, identified 275 deaths among the 42812 kidney transplant recipients and 144 deaths among the 16210 candidates. This represents an excess of deaths for both populations, as compared with the same period the two previous years (mean of two previous years: 253 in recipients and 112 in candidates). This difference was integrally explained by COVID-19, which accounted for 44% (122) and 42% (60) of the deaths in recipients and candidates, respectively. Taking into account the size of the two populations and the geographical heterogeneity of virus circulation, we found that the excess of risk of death due to COVID-19 was similar for recipients and candidates in high viral risk area but four-fold higher for candidates in the low viral risk area. Thus, in case of a second epidemic wave, kidney transplantation should be suspended in high viral risk areas but maintained outside those areas, both to reduce the excess of deaths of candidates and avoid wasting precious resources.
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http://dx.doi.org/10.1016/j.kint.2020.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604114PMC
December 2020

Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients.

Kidney Int Rep 2020 Sep 29;5(9):1448-1458. Epub 2020 Jun 29.

Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Introduction: Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation.

Methods: We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort,  = 249) and an independent, prospective multicenter cohort study for validation ( = 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort.

Results: We identified a set of 10 urinary proteins that accurately discriminated patients with ( = 60) and without ( = 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96-1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8-0.93) for discriminating the presence ( = 43) from the absence ( = 348) of ABMR. The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76).

Conclusions: We identified and validated a urinary protein biomarker set that can be used to exclude ABMR.
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http://dx.doi.org/10.1016/j.ekir.2020.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486186PMC
September 2020

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

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

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

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging.
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http://dx.doi.org/10.1016/j.kint.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444636PMC
December 2020

Transcriptional Changes in Kidney Allografts with Histology of Antibody-Mediated Rejection without Anti-HLA Donor-Specific Antibodies.

J Am Soc Nephrol 2020 09 8;31(9):2168-2183. Epub 2020 Jul 8.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Katholieke Universiteit (KU) Leuven, Leuven, Belgium

Background: Circulating donor-specific anti-HLA antibodies (HLA-DSAs) are often absent in serum of kidney allograft recipients whose biopsy specimens demonstrate histology of antibody-mediated rejection (ABMR). It is unclear whether cases involving ABMR histology without detectable HLA-DSAs represent a distinct clinical and molecular phenotype.

Methods: In this multicenter cohort study, we integrated allograft microarray analysis with extensive clinical and histologic phenotyping from 224 kidney transplant recipients between 2011 and 2017. We used the term ABMR histology for biopsy specimens that fulfill the first two Banff 2017 criteria for ABMR, irrespective of HLA-DSA status.

Results: Of 224 biopsy specimens, 56 had ABMR histology; 26 of these (46.4%) lacked detectable serum HLA-DSAs. Biopsy specimens with ABMR histology showed overexpression of transcripts mostly related to IFN-induced pathways and activation of natural killer cells and endothelial cells. HLA-DSA-positive and HLA-DSA-negative biopsy specimens with ABMR histology displayed similar upregulation of pathways and enrichment of infiltrating leukocytes. Transcriptional heterogeneity observed in biopsy specimens with ABMR histology was not associated with HLA-DSA status but was caused by concomitant T cell-mediated rejection. Compared with cases lacking ABMR histology, those with ABMR histology and HLA-DSA had higher allograft failure risk (hazard ratio [HR], 7.24; 95% confidence interval [95% CI], 3.04 to 17.20) than cases without HLA-DSA (HR, 2.33; 95% CI, 0.85 to 6.33), despite the absence of transcriptional differences.

Conclusions: ABMR histology corresponds to a robust intragraft transcriptional signature, irrespective of HLA-DSA status. Outcome after ABMR histology is not solely determined by the histomolecular presentation but is predicted by the underlying etiologic factor. It is important to consider this heterogeneity in further research and in treatment decisions for patients with ABMR histology.
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http://dx.doi.org/10.1681/ASN.2020030306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461663PMC
September 2020

Diagnostic performance of kSORT, a blood-based mRNA assay for noninvasive detection of rejection after kidney transplantation: A retrospective multicenter cohort study.

Am J Transplant 2021 02 4;21(2):740-750. Epub 2020 Aug 4.

French National Institute of Health and Medical Research (Inserm) Unit 1111, Lyon, France.

The Kidney Solid Organ Response Test (kSORT) blood gene expression assay was developed to noninvasively detect acute rejection (AR) after kidney transplantation. Its performance in a setting with natural disease prevalence has not been evaluated. A retrospective, multicenter cohort study was conducted across all single kidney transplant recipients, transplanted between 2011 and 2015, with samples within the first year after transplantation available in existing biobanks. The primary objective was to determine the diagnostic performance of the kSORT assay to detect AR (T cell-mediated and/or antibody-mediated rejection) as compared to a concomitant renal biopsy. AR was reported on the concomitant biopsy in 188 of 1763 (10.7%) blood samples and any rejection (including borderline changes) in 614 of 1763 (34.8%) blood samples. In 320 of 1763 samples (18.2%) the kSORT risk category was indeterminate. The kSORT assay had no diagnostic value for AR (area under the curve [AUC] 0.51, 95% confidence interval [CI] 0.50-0.56; P = .46) overall, or when considering indication biopsies (N = 487) and protocol-specified biopsies (N = 1276) separately (AUC of 0.53, 95% CI 0.50-0.59, P = .44 and 0.55, 95% CI 0.50-0.61, P = .09, respectively). This large retrospective study utilizing samples obtained under real-world clinical conditions, was unable to validate the kSORT assay for detection of AR in the first year after transplantation.
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http://dx.doi.org/10.1111/ajt.16179DOI Listing
February 2021

Antibody-mediated rejection with and without donor-specific anti-human leucocyte antigen antibodies: performance of the peripheral blood 8-gene expression assay.

Nephrol Dial Transplant 2020 08;35(8):1328-1337

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.

Background: Recently a peripheral blood 8-gene expression assay was developed for non-invasive detection of antibody-mediated rejection (ABMR) after kidney transplantation. Its value has not yet been evaluated in detail in clinical scenarios with different baseline disease probability [human leucocyte antigen donor-specific antibodies (HLA-DSA)-positive versus HLA-DSA-negative cases at the time of stable graft function versus graft dysfunction].

Methods: Here we investigated the diagnostic accuracy of the 8-gene expression assay for histology of ABMR (ABMRh) with or without HLA-DSA in a cross-sectional cohort study of 387 blood samples with a concomitant graft biopsy.

Results: In patients with HLA-DSA (n = 64), the 8-gene expression assay discriminated DSA-positive ABMRh (DSAposABMRh) cases (n = 16) with good diagnostic performance {area under the receiver operating characteristic curve [AUROC] 83.1% [95% confidence interval (CI) 70.8-95.3]}. Also, in HLA-DSA-negative samples (n = 323), a clinically relevant diagnostic performance for DSAnegABMRh cases was found (n = 30) with an AUROC of 75.8% (95% CI 67.4-84.4). The 8-gene assay did not discriminate DSAposABMRh cases from DSAnegABMRh cases. There was a net benefit for clinical decision-making when adding the 8-gene expression assay to a clinical model consisting of estimated glomerular filtration rate, proteinuria, HLA-DSA and age.

Conclusion: The 8-gene expression assay shows great potential for implementation in the clinical follow-up of high-risk HLA-DSA-positive patients and clinical relevance in HLA-DSA-negative cases.
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http://dx.doi.org/10.1093/ndt/gfaa096DOI Listing
August 2020

1-Methyluric Acid Nephropathy.

Kidney Int Rep 2020 May 22;5(5):737-741. Epub 2020 Feb 22.

Sorbonne Université, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche-S 1155, Assistance Publique des Hôpitaux de Paris Service des Explorations Fonctionnelles Multidisciplinaires, Hôpital Tenon, Paris, France.

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http://dx.doi.org/10.1016/j.ekir.2020.02.1026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210604PMC
May 2020

Immune Checkpoint Inhibitors in Transplantation-A Case Series and Comprehensive Review of Current Knowledge.

Transplantation 2021 Jan;105(1):67-78

Department of Dermatology, AP-HP Hôpital Saint Louis, Université de Paris, INSERM U976, Team 1, HIPI, Paris, France.

Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.
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http://dx.doi.org/10.1097/TP.0000000000003292DOI Listing
January 2021

Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection.

Am J Transplant 2020 12 27;20(12):3462-3476. Epub 2020 Jun 27.

Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09, P = .0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29, P < .001) as well as CXCL10/creatinine (1.17/2.09/1.98, P < .0001 and 1.13/2.21/2.51, P < .001, respectively). An optimized 8-parameter model (recipient age, sex, estimated glomerular filtration rate, donor specific antibodies, UTI, BKV blood viral load, CXCL9, and CXCL10) diagnosed AR with high accuracy (area under the curve [AUC]: 0.85, 95% confidence interval [CI]: 0.80-0.89) and remained highly accurate at the time of screening (AUC: 0.81, 95% CI: 0.48-1) or indication biopsies (AUC: 0.85, 95% CI: 0.81-0.90) and within the first year (AUC: 0.86, 95% CI: 0.80-0.91) or later (AUC: 0.90, 95% CI: 0.84-0.96), achieving AR diagnosis with an AUC of 0.85 and 0.92 (P < .0001) in 2 external validation cohorts. Decision curve analyses demonstrated the clinical utility of the model. Considering confounding factors rather than excluding them, we optimized a noninvasive multiparametric diagnostic model for AR of kidney allografts with unprecedented accuracy.
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http://dx.doi.org/10.1111/ajt.15959DOI Listing
December 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

AA amyloidosis revealing mevalonate kinase deficiency: A report of 20 cases including two new French cases and a comprehensive review of literature.

Semin Arthritis Rheum 2020 12 19;50(6):1370-1373. Epub 2020 Mar 19.

Internal medicine department, Tenon hospital, Assistance Publique - Hôpitaux de Paris, Sorbonne University, 4 rue de la Chine, 75020 Paris, France. Electronic address:

Introduction: Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease that can lead to an inflammatory A amyloidosis (AA).

Methods: To study the occurrence of AA in MKD patients we performed a systemic review of the literature and described two novel patients.

Results: Amyloidosis occurred in 20 MKD patients, renal impairment being always the revealing symptom of AA. Although an accurate prevalence estimation is not possible since exact MKD prevalence is unknown, AA seems rare in MKD (about 6% if we estimate MKD prevalence at 300 patients worldwide). MVK gene study, available in 18 out of the 20 patients, confirmed two pathogenic mutations in all tested individuals. The most frequent genotype was V377I/I268T (n = 9/18). Retrospective search of clinical signs of MKD established, in all patients carrying MVK pathogenic mutations, a disease onset within the first four years of life. Nephrotic syndrome (n = 15), end-stage renal failure (n = 5) or both (n = 8) pointed out kidney amyloidosis. The youngest patient with renal amyloidosis was a European four-year-old girl previously misdiagnosed with PFAPA syndrome. Five patients died of AA amyloidosis despite the use of a biotherapy for two of them; kidney transplant was performed in nine individuals. Colchicine was not effective in any patient. Anti-interleukin-1 anakinra (n = 8), anti TNF etanercept (n = 7) and anti-interleukin 6 tocilizumab (n = 5) treatments were partially effective.

Conclusion: Inflammatory A amyloidosis, a rare complication of MKD, can cause death or necessitate kidney transplantation. Early diagnosis and cytokine blocking biotherapy using anti-IL1, anti-TNF or anti-IL6 agents are required to prevent terminal renal failure.
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http://dx.doi.org/10.1016/j.semarthrit.2020.03.005DOI Listing
December 2020

Efficacy and Safety of Direct Oral Anticoagulants in Kidney Transplantation: A Single-center Pilot Experience.

Transplantation 2020 12;104(12):2625-2631

Service de Néphrologie et Transplantation Adulte, Hôpital Necker-Enfants Malades, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Oral anticoagulation therapy is frequently prescribed to kidney transplant recipients (KTRs) for prevention and treatment of thrombotic events. Over the past 10 y, direct oral anticoagulants (DOACs) have shown similar efficacy with a safety profile equal or superior to that of vitamin K antagonist anticoagulants (VKAs) in the general population. However, little data are available on kidney transplantation.

Methods: We investigated the efficacy (thrombotic events) and safety (hemorrhagic and other adverse events and graft outcomes) of DOACs in a cohort of KTRs with a renal function >30 mL/min. We then compared these patients to a control group treated by VKA.

Results: Fifty-two KTRs treated by DOACs between 2013 and 2018 at Necker Hospital were included. Patients were with a mean age of 62 ± 13 y old and a mean glomerular filtration rate of 59 ± 20 mL/min/1.73m. The major indication was atrial fibrillation (n = 31 [60%]). Apixaban was the most commonly used agent (n = 36 [69%]). No thrombotic complications were reported under DOAC until last follow-up (14.1 ± 13 mo). In comparison to 50 controls under VKA during the same period, the bleeding rate under DOAC was significantly lower (11.5 versus 22.9 per 100 patient-y, P = 0.037) with a hazard ratio of 0.39 (95% confidence interval, 0.19-0.85, P = 0.041). No significant changes in kidney function, rejection rate, or hemoglobin level were reported.

Conclusions: DOACs appear to be effective and safe anticoagulants in KTRs with stable renal function.
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http://dx.doi.org/10.1097/TP.0000000000003168DOI Listing
December 2020

Diagnostic yield of F-FDG PET/CT imaging and urinary CXCL9/creatinine levels in kidney allograft subclinical rejection.

Am J Transplant 2020 05 3;20(5):1402-1409. Epub 2020 Jan 3.

Division of Nephrology, Department of Internal Medicine, University of Liège Hospital, Liège, Belgium.

Subclinical kidney allograft acute rejection (SCR) corresponds to "the unexpected histological evidence of acute rejection in a stable patient." SCR detection relies on surveillance biopsy. Noninvasive approaches may help avoid biopsy-associated complications. From November 2015 to January 2018, we prospectively performed positron emission tomography/computed tomography (PET/CT) after injection of F -fluorodeoxyglucose ( F-FDG) in adult kidney transplant recipients with surveillance biopsy at ~3 months posttransplantation. The Banff-2017 classification was used. The ratio of the mean standard uptake value (mSUVR) between kidney cortex and psoas muscle was measured. Urinary levels of CXCL-9 were concomitantly quantified. Our 92-patient cohort was categorized upon histology: normal (n = 70), borderline (n = 16), and SCR (n = 6). No clinical or biological difference was observed between groups. The mSUVR reached 1.87 ± 0.55, 1.94 ± 0.35, and 2.41 ± 0.54 in normal, borderline, and SCR groups, respectively. A significant difference in mSUVR was found among groups. Furthermore, mSUVR was significantly higher in the SCR vs normal group. The area under the receiver operating characteristic curve (AUC) was 0.79, with 83% sensitivity using an mSUVR threshold of 2.4. The AUC of urinary CXCL-9/creatinine ratios comparatively reached 0.79. The mSUVR positively correlated with ti and acute composite Banff scores. F-FDG-PET/CT helps noninvasively exclude SCR, with a negative predictive value of 98%. External validations are required.
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http://dx.doi.org/10.1111/ajt.15742DOI Listing
May 2020

In situ multiplex immunofluorescence analysis of the inflammatory burden in kidney allograft rejection: A new tool to characterize the alloimmune response.

Am J Transplant 2020 04 11;20(4):942-953. Epub 2019 Dec 11.

Department of Pathology, Necker Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

The exact composition of leukocyte infiltration during kidney allograft rejection is difficult to comprehend and visualize on the same biopsy slide. Using an innovative technology of multiplex immunofluorescence (mIF), we were able to detect simultaneously NK cells, macrophages, and T cells and to determine their intra- or extravascular localization using an endothelial marker. Twenty antibody-mediated rejection (ABMR), 20 T cell-mediated rejection (TCMR), and five normal biopsies were labeled, with automatic leukocyte quantification and localization. This method was compared to a classic NKp46 immunohistochemistry (IHC) with manual quantification and to mRNA quantification. mIF automatic quantification was strongly correlated to IHC (r = .91, P < .001) and to mRNA expression levels (r > .46, P < .021). T cells and macrophages were the 2 predominant populations involved in rejection (48.0 ± 4.4% and 49.3 ± 4.4%, respectively, in ABMR; 51.8 ± 6.0% and 45.3 ± 5.8% in TCMR). NK cells constituted a rare population in both ABMR (2.7 ± 0.7%) and TCMR (2.9 ± 0.6%). The intravascular compartment was mainly composed of T cells, including during ABMR, in peritubular and glomerular capillaries. However, NK cell and macrophage densities were significantly higher during ABMR in glomerular and peritubular capillaries. To conclude, this study demonstrates the feasibility and utility of mIF imaging to study and better understand the kidney allograft rejection process.
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http://dx.doi.org/10.1111/ajt.15699DOI Listing
April 2020

Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation.

Am J Transplant 2020 04 9;20(4):1063-1075. Epub 2019 Dec 9.

Paris University, Necker Research Institute, INSERM U1151, Paris, France.

In kidney transplant recipients (KTRs), scarce evidence has associated low blood bicarbonate levels with mineral metabolic disturbance and reduced allograft survival. However, the contribution of the blood pH to these observations remains unassessed. Equally, little is known about the influence of the blood provenance (arteriovenous fistula vs peripheral vein) on bicarbonate values. We analyzed blood gas parameters in a single-center cohort of 1260 stable KTRs, 3 months after transplantation. Inspection of pO distribution allowed the unambiguous identification of the arterial (N = 914) or venous (N = 346) origin of the samples. In patients with arterial blood samples, 435 (46%) had bicarbonate levels below 22 mmol/L. Among them, 196 (40%) were acidemic (blood pH <7.38). In multivariate analysis, low arterial blood pH was associated with increased blood ionized calcium and phosphate and reduced fibroblast growth factor 23 and calcitriol, but not with outcome. In contrast, low bicarbonate concentration predicted allograft loss independently of measured glomerular filtration rate and other potential confounders (hazard ratio [HR] 1.70; 95% confidence interval [CI] 1.04-2.80). In KTRs, reduced arterial blood bicarbonate levels predict outcome while acidemia is associated with altered mineral metabolism.
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http://dx.doi.org/10.1111/ajt.15686DOI Listing
April 2020

MicroRNA-146a-deficient mice develop immune complex glomerulonephritis.

Sci Rep 2019 10 30;9(1):15597. Epub 2019 Oct 30.

INSERM, U1151, Paris, France.

MicroRNAs (miRNAs) play an important role in the kidneys under physiological and pathological conditions, but their role in immune glomerulonephritis is unclear. miR-146a has been identified as a key player in innate immunity and inflammatory responses, and in the kidney, this miRNA is involved in the response of injured tubular cells. We studied the renal and immune phenotypes of miR-146a and miR-146a mice at 12 months of age, and the results showed that miR-146a mice developed autoimmunity during aging, as demonstrated by circulating antibodies targeting double-stranded DNA and an immune complex-mediated glomerulonephritis associated with a mild renal immune infiltrate. In addition, miR-146a mice showed reduced expression of the transmembrane protein Kim1/Tim1, a key regulator of regulatory B cell (Breg) homeostasis, in the kidney and the immune cells. The numbers of memory B cells and plasmablasts were increased in miR-146a mice compared with the numbers in wild-type mice, whereas Bregs were decreased in number and displayed an altered capacity to produce IL-10. Finally, we showed that miR-146a mice develop an autoimmune syndrome with increasing age, and this syndrome includes immune complex glomerulonephritis, which might be due to altered B cell responses associated with Kim1/Tim1 deficiency. This study unravels a link between miR-146a and Kim1 and identifies miR-146a as a significant player in immune-mediated glomerulonephritis pathogenesis.
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http://dx.doi.org/10.1038/s41598-019-51985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821765PMC
October 2019

[Renal transplantation: Procedure and early follow-up].

Nephrol Ther 2019 Nov 19;15(6):469-484. Epub 2019 Oct 19.

Faculté de médecine, université Paris-Descartes, Université de Paris, 75006 Paris, France; Service de néphrologie et transplantation adulte, hôpital Necker, AP-HP, 149, rue de Sèvres, 75015 Paris, France.

More than fifty years after the success of the two first renal transplantations in Boston and in Necker hospital in Paris, renal transplantation became the treatment of choice of end stage renal failure, because it improves not only the quality of life of the patients but also their long-term survival. In France, more than 3,700 kidney transplantations are performed every year and more than 40,000 patients are living with a functioning kidney allograft. This treatment of end stage renal disease requires a fine-tuned pre-transplant evaluation and a multidisciplinary post-transplant care in order to prevent, to detect and to treat comorbidities and complications of immunosuppression. The ambition of this manuscript is not to describe in an exhaustive way all the aspects of renal transplantation but starting from the experience of a team, recently published data, and national and international guidelines, to try to provide a synthetic and chronological view of the early post-transplant monitoring.
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http://dx.doi.org/10.1016/j.nephro.2019.09.001DOI Listing
November 2019

Acute kidney injury during an ultra-distance race.

PLoS One 2019 25;14(9):e0222544. Epub 2019 Sep 25.

Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris Descartes, Sorbonne Paris Cité University, Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Purpose: Previous studies have noted consequences of ultra-distance trail running on health, but few studies are available regarding the temporal variations of renal biomarker injury during the running. The aim of this study was to assess the of kidney function parameters temporal variation during and on short-term after an ultra-distance race.

Methods: We performed an observational study with 47 subjects participating in an ultra-distance race (80 km). Urine (47 subjects) and blood (21 subjects) samples were serially collected before (baseline-km 0), during (21 and 53 km), on arrival (80 km), and 9 days after the race (d9).

Results: Mean serum creatinine increased during the race from 90±14 μmol/L (km0) to 136±32 μmol/L (km 80-p<0.0001) corresponding to a 52% increase. Mean creatininuria progressively increased from 4.7±4.5 mmol/L (km 0) to 22.8±12.0 mmol/L (km 80) (p<0.0001). Both urinary biomarkers (Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1) of acute kidney injury (AKI) progressively increased during the race (p<0.05 vs baseline). However, after adjustment to urine dilution by urine creatinine, no significant changes remained (p>0.05). On day 9, no significant difference remains in blood and urine biomarkers compared to their respective baseline levels.

Conclusions: During an ultra-distance race, despite an acute and transient increase in the serum creatinine levels, urinary biomarkers of AKI displayed only limited changes with a complete regression on day 9. These results suggest the absence of the short-term impact of an ultra-distance race kidney function.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760777PMC
March 2020