Publications by authors named "Mickaël Bobot"

26 Publications

  • Page 1 of 1

Impact of obesity on survival in COVID-19 ARDS patients receiving ECMO: results from an ambispective observational cohort.

Ann Intensive Care 2021 Nov 15;11(1):157. Epub 2021 Nov 15.

Medecine Intensive Réanimation, Centre hospitalier Universitaire L'Hôpital Nord, Assistance Publique hôpitaux de Marseille, chemin des Bourrely, 13015, Marseille, France.

Background: Since March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival.

Results: Between March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3-10) days. At ECMO initiation, patients had a median PaO:FiO of 71 mmHg (IQR 62-81), median PaCO of 58 mmHg (IQR 51-66) and a median arterial pH of 7.33 (IQR 7.25-7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644-0.934), p = 0.007) and 0.631 (0.462-0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004-1.285), p = 0.044 and 1.187 (1.035-1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance.

Conclusion: In this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.
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http://dx.doi.org/10.1186/s13613-021-00943-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591429PMC
November 2021

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

Clin J Am Soc Nephrol 2021 11;16(11):1665-1675

Agence de la Biomédecine, Registre Renal Epidemiology and Information Network, Saint-Denis, France.

Background And Objectives: Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy.

Design, Setting, Participants, & Measurements: Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation.

Results: In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse.

Conclusions: The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.
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http://dx.doi.org/10.2215/CJN.03190321DOI Listing
November 2021

Kidney biopsy in very elderly patients: indications, therapeutic impact and complications.

BMC Nephrol 2021 Nov 2;22(1):362. Epub 2021 Nov 2.

AP-HM, University Hospital of la Conception, Nephrology and Kidney Transplant Centre, Marseille, France.

Background: Few data is available on the risk/benefit balance of native kidney biopsy (KB) in very elderly patients.

Methods: Multicenter retrospective cohort study in the Aix-Marseille area: the results of KB and medical charts of all patients over 85 years biopsied between January 2010 and December 2018 were reviewed.

Results: 104 patients were included. Median age was 87 years. Indications for KB were: acute kidney injury (AKI) in 69.2% of patients, nephrotic syndrome (NS) with AKI in 13.5%, NS without AKI in 12.5%, and proteinuria in 4.8%. Median serum creatinine was 262 μmol/L, 21% of patients required dialysis at the time of KB. Significant bleeding occurred in 7 (6.7%) patients, requiring blood cell transfusion in 4 (3.8%), and radiological embolization in 1 (1%). The most frequent pathological diagnoses were: non-diabetic glomerular diseases (29.8%, including pauci-immune crescentic glomerulonephritis in 9.6%), hypertensive nephropathy (27.9%), acute interstitial nephritis (16.3%), renal involvement of hematological malignancy (8.7%), and acute tubular necrosis (6.7%). After KB, 51 (49%) patients received a specific treatment: corticosteroids (41.3%), cyclophosphamide (6.7%), rituximab (6.7%), bortezomib (3.8%), other chemotherapies (3.8%). Median overall survival was 31 months.

Conclusions: KB can reveal a diagnosis with therapeutic impact even in very elderly patients. Severe bleeding was not frequent in this cohort, but KB may have not been performed in more vulnerable patients.
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http://dx.doi.org/10.1186/s12882-021-02559-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561868PMC
November 2021

Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real-world Data Results from the AlcalUN Study.

Clin Pharmacol Ther 2021 Sep 26. Epub 2021 Sep 26.

Club des Jeunes Néphrologues, Paris, France.

Oral alkalization with sodium bicarbonate (NaHCO ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO -containing or no-NaHCO -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO is no longer associated with an ECV increase compared to citrate in real-life settings.
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http://dx.doi.org/10.1002/cpt.2427DOI Listing
September 2021

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

J Nephrol 2021 Aug 23. Epub 2021 Aug 23.

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

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

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

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

Conclusions: The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.
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http://dx.doi.org/10.1007/s40620-021-01127-6DOI Listing
August 2021

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m seems sufficient.

Nefrologia (Engl Ed) 2021 Aug 2. Epub 2021 Aug 2.

Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Marseille, France; C2VN, INSERM, INRAE, Aix Marseille Université, Marseille, France. Electronic address:

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m, instead of the usual dose of 3500mg/m, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m as a viable therapeutic modality in ESRD patients.
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http://dx.doi.org/10.1016/j.nefro.2021.03.004DOI Listing
August 2021

VITADIAL "Does correction of 25 OH-VITAmin D with cholecalciferol supplementation increase muscle strength in hemoDIALysis patients?": study protocol for a randomized controlled trial.

Trials 2021 May 25;22(1):364. Epub 2021 May 25.

Aix Marseille Univ, School of medicine - La Timone Medical Campus, EA 3279: CEReSS - Health Service Research and Quality of life Center, Marseille, France.

Background: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength.

Methods/design: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective.

Discussion: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength.

Trial Registration: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.
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http://dx.doi.org/10.1186/s13063-021-05302-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146204PMC
May 2021

Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study.

Am J Nephrol 2021 29;52(2):131-140. Epub 2021 Mar 29.

Université de Paris, Paris, France.

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD.

Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients' records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination.

Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1-4 respectively. Conversely, no patient who underwent KB for indications 5-7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group.

Conclusion: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.
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http://dx.doi.org/10.1159/000514259DOI Listing
November 2021

[ESUR recommendations on the use of contrast media: Practice survey, review and commentary by CJN, FIRN and SFNDT].

Nephrol Ther 2021 Apr 5;17(2):80-91. Epub 2021 Feb 5.

Commission Néphrologie Clinique de la SFNDT, 24, Montée des Roches, Saint-Sorlin, 69440 Chabanière, France; Service de néphrologie, hémodialyse, transplantation rénale, lithiase rénale, hypertension artérielle, unité de surveillance continue, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France.

Contrast media administration is classically considered to cause or worsen kidney failure. Recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. The present work evaluates the practice of French nephrologists, and provides a commentary on these recommendations based on an updated review of the literature. We conducted survey among French nephrologists, using an electronic questionnaire distributed by the Société Francophone de Néphrologie, Dialyse et Transplantation, the French Intensive care Renal Network and the Club des Jeunes Néphrologues. 266 responses were collected. The European Society of Urogenital Radiology guidelines are poorly known among the panel of nephrologists. Their practices differ from the guidelines by the more frequent and earlier implementation of measures to prevent renal failure post contrast media. In accordance with the guidelines, hydration is prescribed as a first-line preventive measure, mainly with saline and bicarbonate. Inhibitors of the renin-angiotensin-aldosterone system are frequently discontinued before an injection of contrast media, contrary to what is recommended. In conclusion, the European Society of Urogenital Radiology guidelines, which the working group endorses, but which are still too little known and applied in clinical nephrology in France, prompt nephrologists to lift some of the restrictions on the use of PCI as well as on the continuation of ARS inhibitors before injecting PCI.
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http://dx.doi.org/10.1016/j.nephro.2020.10.011DOI Listing
April 2021

Kidney and contrast media: Common viewpoint of the French Nephrology societies (SFNDT, FIRN, CJN) and the French Radiological Society (SFR) following ESUR guidelines.

Diagn Interv Imaging 2021 Mar 30;102(3):131-139. Epub 2021 Jan 30.

Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000 Rouen, France.

Contrast medium administration is classically considered to cause or worsen kidney failure, but recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. Kidney injury does not constitute a contra-indication to the administration of iodinated contrast medium, as long as the benefit-risk ratio justifies it. Intravenous hydration with 0.9% NaCl or 1.4% sodium bicarbonate is the only validated measure for the prevention of post-iodine contrast nephropathy. This is necessary for intravenous or intra-arterial administration of iodinated contrast agent without first renal pass when the glomerular filtration rate is less than 30mL/min/1.73m, for intra-arterial administration of iodinated contrast agent with first renal passage when the glomerular filtration rate is less than 45mL/min/1.73m, or in patients with acute renal failure. The use of iodinated contrast medium should allow the carrying out of relevant examinations based on an analysis of the benefit-risk ratio and the implementation of measures to prevent toxicity when necessary.
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http://dx.doi.org/10.1016/j.diii.2021.01.007DOI Listing
March 2021

Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients.

Nephrol Ther 2021 Feb 13;17(1):42-49. Epub 2021 Jan 13.

Aix-Marseille University, Department of Nephrology, AP-HM, La Conception Hospital, 147, boulevard Baille, 13005 Marseille, France.

Introduction: There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management.

Objective: We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard.

Methods: Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method).

Results: Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a κ of 0.79. Only orthopnoea (P=0.008), jugular turgor (P=0.005) and hepatic-jugular reflux (P=0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload.

Conclusions: Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation.
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http://dx.doi.org/10.1016/j.nephro.2020.10.008DOI Listing
February 2021

Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19.

J Clin Med 2020 Dec 22;10(1). Epub 2020 Dec 22.

Centre of Nephrology and Renal Transplantation, Hôpital de la Conception, CHU de Marseille, 13005 Marseille, France.

Background: Daily management to shield chronic dialysis patients from SARS-CoV-2 contamination makes patient care cumbersome. There are no screening methods to date and a molecular biology platform is essential to perform RT-PCR for SARS-CoV-2; however, accessibility remains poor. Our goal was to assess whether the tools routinely used to monitor our hemodialysis patients could represent reliable and quickly accessible diagnostic indicators to improve the management of our hemodialysis patients in this pandemic environment.

Methods: In this prospective observational diagnostic study, we recruited patients from La Conception hospital. Patients were eligible for inclusion if suspected of SARS-CoV-2 infection when arriving at our center for a dialysis session between March 12th and April 24th 2020. They were included if both RT-PCR result for SARS-CoV-2 and cell blood count on the day that infection was suspected were available. We calculated the area under the curve (AUC) of the receiver operating characteristic curve.

Results: 37 patients were included in the final analysis, of which 16 (43.2%) were COVID-19 positive. For the day of suspected COVID-19, total leukocytes were significantly lower in the COVID-19 positive group (4.1 vs. 7.4 G/L, = 0.0072) and were characterized by lower neutrophils (2.7 vs. 5.1 G/L, = 0.021) and eosinophils (0.01 vs. 0.15 G/L, = 0.0003). Eosinophil count below 0.045 G/L identified SARS-CoV-2 infection with AUC of 0.9 [95% CI 0.81-1] ( < 0.0001), sensitivity of 82%, specificity of 86%, a positive predictive value of 82%, a negative predictive value of 86% and a likelihood ratio of 6.04.

Conclusions: Eosinophil count enables rapid routine screening of symptomatic chronic hemodialysis patients suspected of being COVID-19 within a range of low or high probability.
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http://dx.doi.org/10.3390/jcm10010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792772PMC
December 2020

Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.

Nephrol Dial Transplant 2021 04;36(5):804-810

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.

Background: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats.

Methods: Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49.

Results: Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67).

Conclusions: 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.
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http://dx.doi.org/10.1093/ndt/gfaa374DOI Listing
April 2021

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

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

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

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

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

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

Conclusions: COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.
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http://dx.doi.org/10.1093/ckj/sfaa199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743188PMC
October 2020

Regional anticoagulation with calcium-free dialysate containing citrate in chronic haemodialysis patients.

Nephrol Dial Transplant 2021 03;36(4):745-746

Centre of Nephrology and Renal Transplantation, Hôpital de la Conception, CHU de Marseille, Marseille, France.

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http://dx.doi.org/10.1093/ndt/gfaa365DOI Listing
March 2021

Combination of Alcohol and EVOH as a New Embolic Agent: Midterm Tissue and Inflammatory Effects in a Swine Model.

Radiol Res Pract 2020 23;2020:8831060. Epub 2020 Oct 23.

Diagnostic and Interventional Radiology Section, Department of Medical Imaging, University Hospital Timone APHM, 278 Rue Saint-Pierre, Marseille 13005, France.

Objective: To evaluate the vascular occlusion and midterm tissue toxicity properties of a combination of ethylene-vinyl alcohol (EVOH) (Squid 18®) (75%) and alcohol (25%)-Alco-Squid 18-in a swine model.

Materials And Methods: Alco-Squid 18 (75% Squid 18® mixed with 25% alcohol) (AS18) was compared to embolization with 96% alcohol alone and to embolization with Squid 18® (S18®) alone. An arteriovenous malformation (AVM) model was created in group 1 ( = 2). Each AVM model was then embolized with AS18 or S18® alone with evaluation of a ratio between the volume of embolic agent divided by the volume of the AVM (evaluated by CT). For group 2 ( = 5), each agent was tested on three different kidneys (upper pole kidney artery). Pre- and postinterventional CTs, angiographies, blood alcohol content dosages, and histological studies (3 months postintervention) were performed.

Results: AS18 has better distal distribution than S18® alone, both in the kidneys (mean capsule-S18® distance: 3.9 mm (±0.23) and mean capsule-AS18 distance: 2.3 mm (±0.11) (=0.029) and in the AVM model. Histological exploration found a higher rate of tubular necrosis with AS18 compared with S18® alone and alcohol alone (3.78 ± 0.44 compared to 2.33 ± 1.22 ( = 0.012) and 1.22 ± 0.67 (  < 0 .0001)). The blood alcohol content was negligible in all cases.

Conclusion: AS18 can suggest a better distal sclerotic and embolic character as compared with S18® alone without systemic toxicity.
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http://dx.doi.org/10.1155/2020/8831060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605951PMC
October 2020

Pseudotumoral calcinosis in a haemodialysis patient.

J Nephrol 2020 10 25;33(5):1115-1116. Epub 2020 Aug 25.

Centre de Néphrologie et Transplantation Rénale, CHU de la Conception, AP-HM, Marseille, France.

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http://dx.doi.org/10.1007/s40620-020-00827-9DOI Listing
October 2020

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BMC Nephrol 2020 07 9;21(1):260. Epub 2020 Jul 9.

AP-HM, Department of Nephrology, Hopital de la Conception, Marseille, France.

Background: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy.

Methods: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018.

Results: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis.

Conclusion: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.
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http://dx.doi.org/10.1186/s12882-020-01911-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350584PMC
July 2020

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease.

BMC Med Genet 2020 06 26;21(1):137. Epub 2020 Jun 26.

AP-HM, Centre de Néphrologie et Transplantation Rénale, CHU de la Conception, AP-HM, Marseille, France.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes.

Case Presentation: The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes' lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography.

Conclusions: We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.
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http://dx.doi.org/10.1186/s12881-020-01071-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320597PMC
June 2020

Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.

J Am Soc Nephrol 2020 07 11;31(7):1509-1521. Epub 2020 Jun 11.

Centre Européen de recherche en Imagerie Médicale, Aix Marseille Université, Centre National de la Recherche Scientifique, Marseille, France

Background: Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells.

Methods: To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of Tc-DTPA, an imaging marker of blood-brain barrier permeability.

Results: In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between Tc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR knockout mice were protected against indoxyl sulfate-induced blood-brain barrier disruption and cognitive impairment.

Conclusions: AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD.
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http://dx.doi.org/10.1681/ASN.2019070728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350986PMC
July 2020

Paradoxical association between blood modular interferon signatures and quality of life in patients with systemic lupus erythematosus.

Rheumatology (Oxford) 2020 08;59(8):1975-1983

C2VN, INRA 1263, INSERM 1260, Aix-Marseille Université, Marseille, France.

Objectives: Blood transcriptomic IFN signature is a hallmark of SLE. The impaired health-related quality of life (HRQOL) observed in SLE is poorly related to disease activity. The aim of this study was to test how IFN signatures were associated with HRQOL in SLE patients.

Methods: Among consecutive patients, blood transcriptomic profiles were analysed with a modular framework comprising 3 IFN modules: M1.2, M3.4 and M5.12. Disease activity was evaluated by the SLEDAI score, and HRQOL was assessed with the SF-36 questionnaire, which includes eight domains: physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (MH) and physical component summary and mental component summary scores.

Results: A total of 57 SLE patients were evaluated, among whom 27 (47%) were clinically quiescent, 30 (53%) were flaring, and 19 (33%) had active lupus nephritis. All SF-36 domains were altered in SLE patients compared with the general French population (P < 0.0001). In multivariate analysis, taking into account flares, age, ethnicity, smoking and renal severity, social functioning was independently associated with the IFN score (P = 0.027). Analyses restrained to quiescent patients (n = 27) yielded greater associations between social functioning and the three IFN modules, and between MH and M3.4. Considering all quiescent visits (n = 51), the IFN score was independently correlated with social functioning (P = 0.022) and MH (P = 0.038).

Conclusion: This unexpected paradoxical association between IFN signature and some specific HRQOL domains argues against a pivotal role of IFNs in the persistently altered HRQOL of SLE patients.
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http://dx.doi.org/10.1093/rheumatology/kez541DOI Listing
August 2020

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case report.

Medicine (Baltimore) 2018 Apr;97(15):e0297

Service of Nephrology and Renal Transplantation, La Conception University Hospital, Boulevard Baille, Marseille, France Department of Internal Medicine, Rehabilitation and Geriatrics, Service of Internal Medicine, Geneva University Hospitals, rue Gabrielle Perret-Gentil, Geneva, Switzerland Department of Pathology and Immunology, rue Michel Servet, Geneva, Switzerland Department of Radiology Department of Pathology Department of Cardiology, La Timone University Hospital, rue Saint Pierre Marseille, France.

Rationale: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy.

Patient Concerns: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione.

Diagnoses: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome.

Intervetions: The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started.

Outcomes: Clinical improvement ensued. At follow-up the patient is well.

Lessons: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.
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http://dx.doi.org/10.1097/MD.0000000000010297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908584PMC
April 2018

Pulmonary embolism induced by methotrexate in a dermatomyositis patient.

Joint Bone Spine 2017 07 19;84(4):501-502. Epub 2016 Sep 19.

Service de Médecine interne, Hôpital de La Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France.

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http://dx.doi.org/10.1016/j.jbspin.2016.07.010DOI Listing
July 2017

International Multi-Specialty Delphi Survey: Identification of Diagnostic Criteria for Hepatic and Renal Cyst Infection.

Nephron 2016 3;134(4):205-214. Epub 2016 Sep 3.

Background: Cyst infection is one of the complications of autosomal dominant polycystic kidney disease and polycystic liver disease. The diagnosis is typically made on a mix of clinical, laboratory and imaging abnormalities but the importance of individual items is uncertain. We aimed to perform a Delphi survey amongst physicians to achieve consensus on diagnostic criteria.

Methods: We retrieved diagnostic items from the literature and conducted physician and patient interviews. All items were combined to create the online questionnaire. Participants rated each item during 3 consecutive rounds. Items were rated for diagnostic helpfulness for hepatic and renal cyst infection on a 9-point scale with anchors, from extremely unimportant (n = 1) to extremely important (n = 9). We determined consensus with the disagreement index. The median rating of each item was calculated and categorized into inappropriate (≤3.4), uncertain (3.5-6.4) or appropriate (≥6.5). By combining all items that reached an appropriate consensus rating, we developed a diagnostic algorithm based on expert consensus.

Results: We invited 58 physicians to participate in the survey. In total, 35 (60%) responded to round 1 of which 91% (n = 32) and 86% (n = 30) responded to round 2 and 3, respectively. The final panel included 23 nephrologists, 5 hepatologists, a nuclear medicine specialist and an infectious disease physician from 11 countries (male 67%, mean age 47 ± 11 years, median clinical experience 21 years). The panel rated the diagnostic helpfulness of 59 potential items. Ultimately, 22 hepatic and 26 renal items were rated appropriate, including positive blood cultures and fluorodeoxyglucose positron-emission CT imaging. Ultrasonography and absence of intracystic bleeding were amongst those deemed uncertain or inappropriate. Subsequently, by combining items rated appropriate, we developed a clinical tool to diagnose hepatic and renal cyst infection.

Conclusions: We identified diagnostic items for hepatic and renal cyst infection and developed an expert-based diagnostic algorithm, which may aid physicians in the diagnostic work-up. A prospective study is necessary to validate this algorithm.
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http://dx.doi.org/10.1159/000446664DOI Listing
March 2017
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