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Background Creatinine-based equations such as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are recommended for estimating GFR (eGFR) in clinical practice but have reduced performance in advanced stages of CKD. However, rare studies have evaluated the performance of eGFR by measuring the average of the urinary clearances of creatinine and urea (mClUN-cr) compared to the eGFR equations. Methods This cross-sectional study evaluated the usefulness of mClUN-cr in a population of 855 participants who performed a GFR measurement by urinary inulin clearance. The performance of mClUN-cr was compared with those of CKD-EPI 2009, CKD-EPI 2021, considering three criteria: bias, precision, and accuracy. Results In the whole sample, the mClUN-cr performed similarly to CKD-EPI equations (2009 and 2021) (precision: 11.5 [95% CI: 10.5; 12.5] vs. 19.0 [95% CI: 17.2; 20.1] and 19.1 [95% CI:17.4; 20.4]), and accuracy P30: 97.0 [95% CI: 95.8; 98.0] vs. 82.0 [95% CI: 79.2; 84.4] and 77.2 [95% CI: 74.5; 80.0]). The CKD-EPI equations (2009 and 2021) had the best performance when mGFR > 60 mL/min/1.73m2. In contrast, the mClUN-cr performed better than others, with lowest mGFR values, more noticeable when mGFR < 60 mL/min/1.73m2. Conclusions The study described the best performance of mClUN-cr at GFR levels below 60 mL/min/1.73m2 and a satisfactory result in the overall cohort. The findings point to a role of this tool, especially for estimating GFR in Chronic Kidney Disease patients in developing countries, when reference measurement of GFR is not available.

Patients on maintenance hemodialysis (MHD), which are at high risk of infection by SARS-CoV-2 virus and death due to COVID-19, have been prioritized for vaccination. However, because they were excluded from pivotal studies and have weakened immune responses, it is not known whether these patients are protected after the “standard” two doses of mRNA vaccines. To answer this, anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured in the circulation 10-14 days after the second injection of BNT162b2 vaccine in 106 patients receiving MHD (14 with history of COVID-19) and compared to 30 healthy volunteers (four with history of COVID-19). After vaccination, most (72/80, 90%) patients receiving MHD naïve for the virus generated at least one type of immune effector, but their response was weaker and less complete than that of healthy volunteers. In multivariate analysis, hemodialysis and immunosuppressive therapy were significantly associated with absence of both anti-RBD IgGs and anti-spike CD8+ T cells. In contrast, previous history of COVID-19 in patients receiving MHD correlated with the generation of both types of immune effectors anti-RBD IgG and anti-spike CD8+ T cells at levels similar to healthy volunteers. Patients receiving MHD naïve for SARS-Cov-2 generate mitigated immune responses after two doses of mRNA vaccine. Thus, the good response to vaccine of patients receiving MHD with a history of COVID-19 suggest that these patients may benefit from a third vaccine injection., Graphical abstract

(1) Background: The Vaccine Coverage Rate of influenza remains low and omnichannel efforts are required to improve it. The objective was to evaluate the feasibility and outcomes of a QR Code nudging system in outpatient departments. (2) Methods: The study was performed in 6 departments ensuring ambulatory activities in a French university Hospital between November and December 2021. By scanning QR codes, users accessed anonymously to the ELEFIGHT

International audience; Since the first attempt at extracorporeal renal replacement therapy, renal replacement therapy has been constantly improved. In the field of hemodialysis, substantial efforts have been made to improve toxin removal and biocompatibility. The advent of hemodiafiltration (HDF) and, more recently, of mid cut-off membranes have contributed to management of patients with end-stage renal disease (ESRD). Although several uremic toxins have been discovered, we know little about the clinical impact of their clearance in hemodialysis patients. In addition, a great deal of progress has been made in the areas of filtration and diffusion, but the adsorptive properties of hemodialysis membranes remain under-studied. The mechanism of action of adsorption is based on the attraction between the polymer of the dialysis membrane and the solutes, through hydrophobic interactions, ionic or electrostatic forces, hydrogen bonds or van der Waals forces. Adsorption on the dialysis membrane depends on the membrane surface, pore size, structure and electric load. Its involvement in toxin removal and biocompatibility is significant, and is not just an epiphenomenon. Diffusive and convective properties cannot be improved indefinitely and high permeability membranes, despite their high performance in the clearance of many toxins, have several limitations for long-term use in hemodialysis. This review will discuss why adsorption should be reconsidered and better characterized to improve efficiency and adequacy of dialysis.

This study aims at evaluating fluconazole exposure in critically ill patients and identifying variables associated with the latter.This was a 2-year (2018-2019) retrospective multicenter cohort study. Adult patients 18 years-old with at least one fluconazole concentration measurement during their ICU stay were included.Twenty patients were included. Only 11 patients had a fluconazole trough concentration (Cmin) within the target range (≥15 mg/L). According to bivariable analysis, SOFA score, GGT, fluconazole clearance, Ke, and Vd, were independently associated with a decrease in fluconazole Cmin. The median loading dose required to achieve the Cmin target appeared to be greater in patients with higher SOFA or GGT level and in patients undergoing renal replacement therapy.This study supports recommendation for routine fluconazole therapeutic drug monitoring in ICU patients so as to avoid underexposure, especially if SOFA score is ≥ 7 and/or GGT is ≥ 100 U/L.

Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract

The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% patients with negative spike-specific CD4+ T cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4+ T cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2 naïve patients receiving MHD., Graphical abstract

BackgroundPatients on maintenance hemodialysis (MHD) are at high risk of infection with SARS-Cov-2 and death due to COVID-19. This vulnerable population has been prioritized for vaccination, but the level of protection achieved in these immunocompromised patients is unclear.ObjectivesTo evaluate the protection of MHD patients against COVID-19 after 2 doses (2D) of BNT162b2, and the safety and impact on immune responses of a 3rddose (3D).DesignProspective observational.Setting, Patients, intervention and measurementsREIN national registry was used to compare the severity of 1474 cases of COVID-19 diagnosed in MHD patients after 0, 1 or 2 doses of mRNA vaccine. Anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured after 2D and 3D of BNT162b2 in a monocentric cohort of 75 MHD patients.ResultsVaccination reduced disease severity but 11% of MHD patients infected after 2D still died. Tolerance to 3D of BNT162b2 was excellent. MHD patients with humoral response similar to healthy volunteers after 2D did not generate more immune effectors after 3D and had more side effects. In contrast, 2/3 of MHD patients with suboptimal response after 2D reached optimal titer of anti-RBD IgG and/or developed spike-specific CD8+ T cells after 3D. Presence of spike-specific CD4+ T cells after 2D was associated with response to 3D in multivariate analysis (OR=4.80 [1.23−21.54]; p=0.029).LimitationsLimited number of patients injected with 3D.ConclusionStandard scheme of vaccination provides insufficient protection to some MHD patients. Anti-RBD IgG and specific CD4+ T cells should be measured after 2D. Among patients with suboptimal humoral response, those with specific CD4+ T cells could benefit of a 3rddose of vaccine.RegistrationNCT04881396Funding SourceNone

International audience; Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Introduction: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3–5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l’Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.

Background and Aims Among ST-segment elevation myocardial infarction (STEMI) patients, the respective impact of the baseline renal function, of the development of acute kidney injury (AKI), and of their combination, on the long-term cardiovascular outcomes, remain unclear. Method The present study was based on a post hoc analysis of the CIRCUS trial database, a multicentre randomized study which gathered 969 patients with anterior STEMI treated by primary percutaneous intervention (PPCI) within 12 hours of symptoms onset. Uni and multivariate regressions were performed to identify if the estimated glomerular filtration rate (eGFR) at admission and the development of AKI were associated with (1) cardiovascular death and heart failure (HF) at one year and (2) sub-optimal treatment prescription at discharge. Results A total of 822 patients were included. The mean baseline eGFR was 86 ± 19 mL/min/1.73m2. AKI occurred in 97 patients (11.8%). Baseline eGFR Conclusion In anterior STEMI patients undergoing PPCI, the development of AKI was the strongest independent predictor of poor clinical outcome at one year. The study suggests the need for a tailored monitoring of STEMI patients with AKI or baseline kidney dysfunction.

Background and Aims Renal ischemia-reperfusion can lead to acute kidney injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through inflammation and vascular lesions. Serum urea or creatinine level routinely used as diagnostic indices of renal function are always delayed from the onset of the disease. Therefore, we currently lack reliable markers to early detect AKI, especially in animals. We aimed to show that non-invasive renal contrast-enhanced ultrasound (CEUS) could be a reliable tool to assess early and chronic changes of renal perfusion after renal ischemia-reperfusion. Method Male C57BL6 mice underwent 15 minutes of unilateral renal ischemia by clamping of the left renal vascular pedicle (n = 7), or a sham procedure (n = 3), under inhaled general anesthesia by Sevoflurane. A renal ultrasound was performed on the left ischemic kidney at baseline 1 week before the surgery, then, 20 minutes after reperfusion to assess early modifications of renal perfusion, and 1 month after reperfusion to follow chronic modifications. CEUS was performed in supine position by using a high-resolution ultrasonic imaging system (VEVO 3100 Fujifilm Visualsonics, Toronto, Canada) with a MX550D probe fixed in place with an iron support, ensuring the constant imaging plane throughout acquisition. First, a continuous infusion of microbubbles (VS-11913, Fujifilm Visualsonics, Toronto, Canada) was done through the tail vein, then a high mechanical index burst was given to destroy microbubbles when the contrast enhancement had reached a steady state, and finally, low mechanical-index imaging mode was used until, and 30 sec after the contrast agent concentration reached the plateau. Images were recorded and were analyzed using the “destruction-replenishment” fitting model of the Vevo LAB software (Fujifilm Visualsonics, Toronto, Canada). Renal perfusion was estimated by the total renal Blood Volume (rBV) parameter and was expressed as percentage of the baseline value for each animal. Renal function was also assessed by serum urea concentration 1 month after reperfusion, and the long axis lengths of both the kidneys were measured ex vivo after the mice were euthanized. Results Renal perfusion of the ischemic kidney measured by CEUS was significantly decreased as soon as 20 minutes of reperfusion compared to baseline (median 28,8% of baseline value; interquartiles [20,1 – 69,8%]). 1 month after reperfusion, renal perfusion recovered partially but was still significantly decreased compared to baseline (median 79,9% of baseline value; interquartiles [52,8 – 99,9%]) (Figure A). In sham operated mice, renal perfusion did not differ from baseline at 20 minutes or 1 month (p > 0.05). The renal function, assessed by serum urea, was mildly but significantly impaired 1 month after ischemia-reperfusion compared with sham (median serum urea 9,8 vs. 7,6 mmol/L) (p = 0.02), and this was consistent with the observed kidney atrophy in the ischemic group when compared to the contralateral kidney (median long axis length 7,5 vs 10,8 mm) (p = 0.03). Moreover, the decrease of renal perfusion 20 minutes after reperfusion was significantly correlated with the impairment of renal perfusion 1 month after reperfusion (Pearson r = 0.836, p = 0.005) and with the serum urea level at 1 month (Pearson r = -0.710, p = 0.03) (Figure B-C). Conclusion Renal CEUS was able to detect early impairment of renal perfusion as soon as 20 minutes after 15 minutes of renal ischemia in mice, and perfusion was still decreased 1 month after reperfusion, compared to baseline. This early impairment of perfusion was correlated with the chronic decrease of renal perfusion and renal function 1 month after reperfusion. This was also associated with a significant kidney atrophy. CEUS is an interesting non-invasive tool to assess renal lesions dynamically after ischemia-reperfusion.

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

Aim To assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD). Methods A literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript. Results Of the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials–RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference. Conclusions Within the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function.

International audience

Introduction L’ischemie-reperfusion renale est a l’origine d’une inflammation renale et systemique. Il est suggere un effet protecteur de l’hypothermie moderee. Nous avons dose extracellular Cold-Inducible RNA-binding Protein (eCIRP) plasmatique, une cytokine pro-inflammatoire, apres une ischemie renale avec ou sans hypothermie. Description Une ischemie renale bilaterale de 20 minutes par clampage des pedicules vasculaires renaux a ete menee chez des souris C57BL6 reparties en 4 groupes : un groupe normothermique (IR-37 °C, n = 14) ou hypothermique (IR-34 °C, n = 14), et des groupes controle sans ischemie (Sham-37 °C, n = 10 et Sham-34 °C, n = 10). Methodes Les taux plasmatiques d’uree et de eCIRP ont ete mesurees a 2 h et 24 h de reperfusion. Les reins ont ete preleves a 24 h pour analyse histologique (score de necrose tubulaire aigue de 0 a 4). Resultats L’ischemie-reperfusion a 37 °C (groupe IR-37 °C) entraine une augmentation de l’uree des 2 h et a 24 h de reperfusion comparee aux Sham (p L’hypothermie moderee au cours de l’ischemie (groupe IR-34 °C) empeche l’elevation de l’uree a 2 h de reperfusion, limite l’insuffisance renale aigue a 24 h (p = 0,001), les lesions histologiques renales (score median 1,45, p Dans notre modele, eCIRP est correlee au taux d’uree des 2 h (Spearman r = 0,60, p Fig. 1 ). Conclusion L’ischemie-reperfusion renale entraine une augmentation de eCIRP plasmatique, correlee a l’insuffisance renale aigue et aux lesions histologiques renale, qui sont limitees par une hypothermie moderee (34 °C) pendant l’ischemie. eCIRP pourrait etre un bon biomarqueur plasmatique precoce des lesions d’ischemie-reperfusion renale, et des mesures de nephroprotection comme l’hypothermie.

In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed.A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round).Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins).The panel expressed a need for new treatment strategies validated by clinical trials.

International audience

Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I&ndash, II to CKD stage IV&ndash, V compared to non-CKD patients (4.5-fold higher in CKD IV&ndash, V, p &lt, 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV&ndash, V patients (6.2-fold, p &lt, 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p &lt, 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV&ndash, V patients before the initiation of hemodialysis.

Background and Aims Glomerulonephritis is common in ANCA associated vasculitis (GN-AAV). There is extensive published data on the renal prognosis of these conditions. However, few authors have described predictive factors for end-stage renal disease (ESRD) in patients with GN-AAV. Many authors suggest that renal biopsy should be abandoned in patients whose diagnosis would be established by antibody positivity alone. The aim of the study was to establish a prognostic score for renal damage during ANCA vasculitis and demonstrate need for prognostic renal biopsy. Method One Hundred and eighteen patients referred to 2 french nephrology departments in Lyon between January 2003 and January 2019 were retrospectively analysed. Patients were randomly divided in 2 cohorts at a ratio of 70/30: training and validation cohorts. ESRD was defined as glomerular filtration rate (eGFR) ≤ 15mL/min/1.73m2,need of chronic dialysis or renal transplantation. Results Of the 118 patients, 38 (32.20%) developed ESRD. We identified 3 criteria associated with development of ESRD in patients with GN-AAV. One point was assigned to each criterion according to a threshold value: eGFR at the time of renal biopsy ≤ 15 mL/min; percentage of sclerotic glomeruli ≥ 11% and percentage of normal glomeruli < 20%. A new prognostic renal score was established in patients with GN-AAV. It classifies patients into 3 categories at risk of developing ESRD: low (≤ 1 point), moderate (2 points) and high (3 points). Conclusion Two of the three criteria of our score are histological. Biopsy remains, when possible, an essential tool for diagnosis and especially to predict renal prognosis of ANCA vasculitis with renal impairment.

Background and Aims Fabry Disease (FD) is an X linked lysosomal storage disease due to pathogenic α-galactosidase A (GLA) variants. It leads to damage in kidney and other organs. Numerous prevalence studies have been conducted over the past twenty years in ESRD patients in different countries. However, many screening studies did not perform confirmatory GLA variant analyses, and included recently recognized ‘benign/likely-benign’ variants, thereby inflating prevalence estimates. Thus, the prevalence of Fabry disease in patients with end-stage renal disease remains controversial. The FABRYDIAL study aimed to measure the prevalence of Fabry disease in patients aged 18 to 75 years and treated by chronic dialysis, either hemodialysis or peritoneal dialysis. Method The study was conducted in France in 5 geographic sectors (Aquitaine, Ile-de-France, Rhône-Alpes and Picardie regions, and the Gard department). One hundred and twenty-four dialysis centers participated in the study, which targeted patients undergoing chronic dialysis during the week of November 20, 2017. The exclusion criteria were the existence of a proven nephropathy unrelated to FD (polycystic kidney disease, type 1 diabetes or biopsy-proven IgA nephropathy, membranous glomerulonephritis or ANCA-associated vasculitis), the absence of health insurance coverage or guardianship or tutelage. α-galactosidase A in men, and both α-galactosidase A and lyso-GL3 in women, were measured on a drop of dried blood during the usual care of patients. GLA gene sequencing was performed in patients in whom one biological value was outside normal values. If a genetic variant was identified, a multidisciplinary Diagnosis Validation Committee (DVC) concluded, based on precise literature, clinical, biological and genetic data, as to the reality of Fabry disease. Results Among the 6,032 patients aged 18 to 75 years under chronic dialysis during the period considered, 714 were no longer treated in the participating centers when the research staff visited for eligibility assessment. 1,121 had non-inclusion criteria, which in 89% of cases were a confirmed diagnosis of kidney disease (by renal biopsy or other means) making the existence of Fabry disease very unlikely. 4,197 patients met the inclusion criteria, of which 3,088 were included (1,888 men and 1,200 women). Valid biological analyzes were available for 2815 patients (1721 men and 1094 women), and a genetic test was indicated for 91 patients (52 men and 39 women). Ninety-seven percent of the samples were analyzed with a unique assay technique in a unique laboratory. Five patients had a genetic variant (4 men and one woman). After discussion in the DVC, one male patient was considered to have a confirmed Fabry disease. He presented early signs of the disease (first-degree family history of cardiac or unexplained death, hypohidrosis, heat intolerance, tendency to chronic diarrhea, angiokeratoma, hypoacousia and tinnitus) which could have been identified earlier. The GLA variant was c.1185dupG / p.Phe396Glyfs, a clearly pathogenic frameshift variant. The prevalence of FD in included patients with biological data was 0.035% [0.006; 0.201] (0.058% [0.010; 0.33] in men, 0.000 % [0,000; 0.350] in women). If we consider that patients who were not included because of a specific renal diagnosis unrelated to FD did not have FD, the estimated prevalence decreased to 0.028% [0.006; 0.121]. Conclusion The estimated prevalence of FD in a cohort of French dialysis patients is 0.035% [0.006; 0.201], and by sex 0.058% in men [0.010; 0.328] and 0,000% in women [0,000; 0.35]. Although it appears extremely low, it remains justified to bring up this diagnosis in the event of an evocative sign, whether for the patient or his relatives as FD benefit of effective specific treatments. Funding for this Investigator Sponsored Study was provided by Sanofi Genzyme

Background and Aims Renal ischemia reperfusion (RIR) can induce mitochondrial stress triggering cell death and eventually leading to acute kidney injury (AKI). It has been suggested that mild hypothermia could be protective in RIR without clear underlying mechanisms. We aimed to show that mild hypothermia (34°C) during RIR protects renal mitochondrial function and prevents AKI. Method Male C57BL6 mice were assigned to 4 groups: normothermic ischemic (RIR-37°C) group (n=14) and hypothermic ischemic (RIR-34°C) group (n=14) with body temperature maintained at respectively 37°C or 34°C during 20 minutes of renal ischemia by bilateral renal clamping under general anesthesia; normothermic sham (Sham-37°C) group (n=10) and hypothermic sham (Sham-34°C) group (n=10) with only anesthesia and laparotomy at 37°C or 34°C respectively. Renal function (serum urea concentration) and isolated renal mitochondria function (capacity of mitochondria to retain calcium i.e. calcic retention capacity (CRC), and oxidative phosphorylation capacity of electron transport chain complexes (complex I, II and IV)) were assessed 2 hours and 24 hours after reperfusion. All animal procedures were approved by local Ethics Committee. Data are presented as median with IQR. Results All the parameters monitored were not modified by the temperature in the sham groups, and there was no mortality in those 2 groups. Mortality was 33% in the RIR-37°C group and 11% in the RIR-34°C group 24 hours after reperfusion (p=0.58). Renal ischemia was responsible for a significant increase of serum urea level 2 hours after reperfusion at 37°C [18.7 (17.3–19.0) mmol/L] compared to sham groups (p=0.02), whereas no significant increase was observed in the RIR-34°C group. After 24 hours of reperfusion serum urea level was improved in the RIR-34°C group [22.7 (11.5–42.0) mmol/L] compared to RIR-37°C [60.8 (58.0–69.7) mmol/L, p=0.001]. CRC was not modified by RIR after 2 hours of reperfusion in both groups. CRC was preserved 24 hours after reperfusion in the RIR-34°C group [260 (210–320) nmol Ca2+/mg protein] with no difference compared to Sham-37°C [320 (280–360) nmol Ca2+/mg protein p=0.18] whereas CRC was significantly decreased in the RIR-37°C group compared to Sham-37°C [120 (0–130) vs 320 (280–360) nmol Ca2+/mg protein p=0.004). Complexes I, II and IV were lowered after 2 hours of reperfusion in the RIR-37°C group (p Conclusion Mild hypothermia (34°C) during RIR significantly protected renal mitochondrial respiration and mitochondrial stress, associated with a preserved renal function after 2 hours of reperfusion and an improved renal function 24 hours after reperfusion compared to normothermic mice (37°C).

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30&ndash, 71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8&ndash, 19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA ([HR] 1.62, 95% [95% CI] 1.07&ndash, 2.44], p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00&ndash, 1.21], p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24&ndash, 7.88], p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

Introduction L’ischemie-reperfusion renale cree des lesions vasculaires aigues, qui peuvent se chroniciser. Notre but etait de montrer que l’echographie renale de contraste permet d’evaluer les anomalies de perfusion renale apres ischemie-reperfusion. Description Une ischemie renale unilaterale de 15 minutes par clampage du pedicule vasculaire renal gauche a ete realisee sur des souris C57BL6 (n = 6), ou une procedure Sham sans ischemie (n = 3). Methodes Une echographie de contraste de perfusion (systeme VEVO 3100, Fujifilm Visualsonics) du rein gauche etait realisee : 1 semaine (basale) avant la chirurgie, puis precocement (20 minutes) et a distance (1 mois) apres reperfusion. Des microbulles (VS-11913, Fujifilm Visualsonic) etaient injectees en continu via la veine caudale, puis detruites par un burst d’ultrasons. Les images etaient acquises jusqu’a 30 secondes apres reascension du signal, puis analysees par le modele « destruction-replenishment » du logiciel VevoLAB (Fujifilm Visualsonics). La perfusion du rein entier etait estimee par le rBV (relative Blood Volume) exprime en pourcentage de la valeur basale de l’animal. A 1 mois de reperfusion, l’uree serique etait dosee. Resultats Chez les souris ischemiques, la perfusion renale etait diminuee des 20 minutes apres reperfusion (rBV median 28,8 % de la basale ; interquartiles [20,1–69,8 %]). A 1 mois de reperfusion, la perfusion renale recuperait mais restait abaissee comparee aux basales (rBV median 79,9 % de la basale ; interquartiles [52,8–99,9 %]). Chez les Sham, la perfusion etait inchangee. L’abaissement precoce de la perfusion renale 20 minutes apres reperfusion etait correlee a la diminution chronique de perfusion renale (Pearson R = 0.836, p = 0,005) et a l’elevation de l’uree (Pearson R = −0,710, p = 0,03) a 1 mois ( Fig. 1 ). Conclusion L’echographie renale de contraste de perfusion est un outil interessant pour evaluer les lesions renales fonctionnelles precocement et a distance apres ischemie-reperfusion.

Introduction Les patients hémodialysés chroniques (HD) sont à haut risque d’infection par le SARS-CoV2 et de décès en cas de COVID-19, justifiant la priorisation de la vaccination dans cette population. Cependant, ces patients étaient exclus des études pivots, et sont connus pour avoir un défaut de réponse vaccinale. Description Il est donc urgent d’établir si les patients HD sont protégés après un schéma vaccinal « standard » par 2 doses de vaccin ARNm. Méthodes Nous avons mesuré le taux d’IgG dirigé contre le domaine de fixation de la protéine Spike (IgG anti-RBD) ainsi que la réponse interféron-gamma (IFNγ) des lymphocytes T CD4 et CD8 spécifiques 10 à 14 jours après la 2nde injection vaccinale chez 106 patients hémodialysés chroniques (dont 14 avec un antécédent de COVID-19). En l’absence de corrélat de protection, nous avons utilisé une cohorte de 30 volontaires sains comme référence. Résultats Dix à 14 jours après la 2nde injection, 19/106 (18 %) des patients n’avaient pas d’IgG anti-RBD, 47/106 (44 %) des IgG anti-RBD détectables mais inférieurs aux volontaires sains, et 40/106 (38 %) un titre d’IgG anti-RBD similaire aux volontaires sains. En analyse multivariée, les facteurs indépendamment associés à une réponse IgG anti-RBD optimale étaient une absence d’immunosuppression (OR = 0,16, p = 0,05), un antécédent de COVID-19 (OR = 9,55 ; p = 0,004) et de meilleurs paramètres d’hémodialyse (OR = 6,11 ; p = 0,014). Les réponses CD4 étaient corrélées aux IgG anti-RBD (p

Introduction Les patients hémodialysés chroniques (HD) présentent un défaut de réponse immunitaire après 2 doses de vaccin ARNm anti SARS-Cov2, ayant conduit les autorités de santé françaises à recommander l’injection d’une 3e dose vaccinale. Description Notre objectif était d’évaluer : – la nécessité clinique ; – la tolérance ; – l’immunogénicité d’une 3e injection vaccinale chez les patients HD. Méthodes Nous avons comparé la gravité des maladies COVID des patients HD non vaccinés, après 1 dose ou 2 dose vaccinale issues du registre national français REIN. Nous avons ensuite mesuré les taux d’IgG anti-RBD et la réponse interféron gamma des lymphocytes T CD4 et CD8 spécifiques 10 à 14 jours après la 3e injection vaccinale chez 56 patients hémodialysés ayant un défaut de réponse après 2 doses. Résultats obtenus ou attendus Entre le 01/02/2021 et le 18/05/2021, 105 cas de COVID-19 sont survenus chez des HD après 2 injections vaccinales, 179 après 1 dose et 1094 chez des HD non vaccinés. Si la vaccination diminue la sévérité de la maladie COVID(p

Resume La microangiopathie thrombotique est une complication rare mais grave du traitement par gemcitabine. Sa prevalence augmente du fait de l’elargissement des indications de cette chimiotherapie. Nous rapportons quatre cas pour lesquels la presentation clinicobiologique est relativement typique, associant hypertension arterielle, proteinurie et augmentation de la creatinine plasmatique. En revanche, la gravite du tableau est variable, necessitant le recours inconstant a une technique d’hemodialyse. Les strategies therapeutiques, outre l’arret systematique de la gemcitabine, ne sont pas consensuelles. Elles ont ete guidees par la gravite du tableau : echanges plasmatiques d’efficacite variable et eculizumab, qui s’est avere efficace lorsqu’il a ete utilise. Il ressort surtout que ce syndrome est compose de signes banals et frequents chez des patients recevant des chimiotherapies, comme les cytopenies et la majoration de la creatinine. Mais ces signes devraient inciter a rechercher d’autres signes plus specifiques, tels qu’une hypertension arterielle, des stigmates d’hemolyse mecanique, une proteinurie ou une hematurie, afin de reconnaitre le plus precocement possible la microangiopathie thrombotique et permettre sa prise en charge rapide, en evitant de nouvelles injections.

Background Clostridium difficile infection (CDI) is a serious medical condition that is associated with substantial morbidity and mortality. Identification of risk factors associated with CDI and prompt recognition of patients at risk is key to successfully preventing CDI. Methods A 3-year prospective, observational, cohort study was conducted in a French university hospital and a nested case-control study was performed to identify risk factors for CDI. Inpatients aged 18 years or older, suffering from diarrhea suspected to be related to CDI, were asked to participate. Results A total of 945 patients were included, of which 233 cases had a confirmed CDI. CDI infection was more common in men (58.4%) (P = 0.04) compared with patients with diarrhea not related to C. difficile. Previous hospitalization (P

Chronic kidney disease causes hyperphosphatemia, which is associated with increased cardiovascular risk and mortality. In patients with end-stage renal disease, haemodialysis allows the control of hyperphosphatemia. During a 4-h haemodialysis session, between 600 and 700mg of phosphate are extracted from the plasma, whereas the latter contains only 90mg of inorganic phosphate. The precise origin of phosphates remains unknown. The modelling of phosphorus transfers allows to predict the outcome after changes in dialysis prescription (duration, frequency) with simple two-compartment models and to describe the transfers between the different body compartments with more complex models. Work using 31P nuclear magnetic resonance spectroscopy performed in animals showed an increase in intracellular phosphate concentration and a decrease in intracellular ATP during a haemodialysis session suggesting an intracellular origin of phosphates.

Endovascular revascularization as treatment of atherosclerotic renal-artery stenosis (aRAS) is controversial since 3 large and multicentric randomised trials (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous transluminal renal-artery stenting (PTRAS) over medical treatment only (MT). However, considering the multiple bias of these trials, among which questionable inclusion criterias, these results must be extrapolated in clinical practice with caution. New pathophysiological data have been helping to understand why restoring blood flow does not necessarily lead to kidney function improvement. Today, the diagnostic approach must in one hand confirm the artery stenosis and on the other hand assess its severity and impact on the kidney. Therapeutic options still lie on the American guidelines published in 2006, since no study data can be reasonably used in everyday practice. However, particular sub-groups of patients who could benefit from revascularisation have been identified through recent cohort studies. Further prospective studies are needed in order to confirm the superiority of PTRAS in these populations. Meanwhile, multidisciplinary approach should be promoted, in order to provide the best treatment for each patient.

Background: In patients with cast nephropathy and acute kidney injury (AKI) requiring dialysis, the reduction of serum free light chains (FLC) using chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may improve renal and patient outcomes. We evaluated the effectiveness of a combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate membrane (IHD-PMMA) on renal recovery and survival. Methods: A single-center retrospective cohort-study was conducted. Between 2007 and 2014, patients with dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA were included. Patients had six 6-h hemodialysis sessions a week, until predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary outcomes were renal recovery, defined as dialysis independence, and survival. Results: Seventeen patients were included, all with stage 3 AKI. All received chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the overall hematological response rate was 57%; hematological response was maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months, 76, 75, and 62% of patients were alive, respectively. Higher reduction in involved FLC by day 12 (p = 0.022) and day 21 (p = 0.003) was associated with renal recovery. Patients with FLC reduction rate >50% by day 21 experienced a lower mortality (hazard ratio 0.10, 95% CI 0.02–0.63). Conclusion: In patients with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA combined with chemotherapy was associated with high rates of renal recovery and survival.

Atherosclerosis is an important predictor of mortality in patients with chronic kidney disease (CKD) and is associated with a wide inflammatory response. The aim of this study is to evaluate in vitro how different membranes can remove mediators associated with this pathology in a closed loop dialysis model. We performed experimental hemofiltration in vitro using three different membrane materials. Human plasma was preliminarily incubated with various inflammatory mediators and filtered in a closed loop circulation model for 240 min. Respective concentrations of 17 different mediators were measured over time to study the removal mechanisms of each membrane, including associated removal time course. The experiment was repeated three times for the assay of tumor necrosis factor (TNF)-α to document the model variability. Means were compared using Mann–Whitney test. Most of the investigated mediators were effectively removed with the different dialysis membranes. Adsorption mechanism was mainly at the origin of the decrease in mediators circulating concentrations and was maximized in the region 10 000–20 000 Da. Especially, the HeprAN membrane showed fast removal capacities of mediators with elevated isoelectric point including complement factors and chemokines or having basic groups located in the protein periphery, plasminogen activator inhibitor (PAI-1), and TNF-α-like. The latter was further significantly removed with HeprAN and polymethylmethacrylate (PMMA) compared to polyethersulfone (PES) material (P