Background: Acute kidney injury (AKI) is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe AKI in critically ill COVID-19 patients. Methods: In this cohort study, data from consecutive patients older than 18 years admitted to 6 ICUs for COVID-19-related ARDS requiring invasive mechanical ventilation were included. The incidence and severity of AKI, defined according to the 2012 KDIGO definition, were monitored during the entire ICU stay until day 90. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included. Results: 164 patients were included in the final analysis; 97 (59.1%) displayed AKI, of which 39 (23.8%) had severe stage 3 AKI, and 21 (12.8%) required renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with angiotensin-converting enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307–13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044–1.241), p = 0.003) and iNO (OR: 5.694 (1.953–16.606), p = 0.001). Prone positioning (OR: 0.234 (0.057–0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053–0.713), p = 0.014) were associated with a decreased risk of severe AKI. Conclusions: Dexamethasone was associated with the prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19-related ARDS.

In chronic intermittent hemodialysis, heparin is the standard anticoagulant as is the use of acid-containing dialysate. Regional anticoagulation (RA) with a calcium-free, citrate-containing dialysate has been developed. We compared RA using a calcium-free, citrate-free dialysate, routinely used in our center, versus systemic heparinization. In a retrospective, observational, single-center, crossover study, we examined 15 patients undergoing chronic hemodialysis who were at high risk of bleeding and temporarily unable to use heparin. These patients received temporary treatment with RA involving calcium-free and citrate-free dialysate. We compared the dialysis session success rates during two distinct periods: standard heparinization and RA procedure with a calcium-free and citrate-free dialysate. In our study of 15 patients on chronic hemodialysis which compared 30 RA sessions versus 28 heparin-based anticoagulation session, we observed a 100% success rate with a median session duration of 240 min in both RA and heparin groups. No early extracorporeal circulation (ECC) loss was reported. However, we noted significant differences in the post-dialysis ECC thrombosis scores, with higher Global Thrombosis Index (GTI) and higher membrane coagulation scores in the RA group (P < .007 and P < .02, respectively). No hypocalcaemia or hypercalcemia symptoms occurred. Median post-filter ionized calcium levels were 0.32 (0.29–0.39) mmol/L at 30 min and median patient ionized calcium levels was 1.19 (1.135–1.28) mmol/L at 60 min. No significant difference in per-dialysis arterial blood pressure was observed between groups. Our study evaluated the RA approach using a calcium-free, citrate-free acetate dialysate in a chronic hemodialysis center and found it effective. Although an acid-free dialysate was not used in this study, our findings suggest it could be the next frontier in the evolution of advanced dialysis techniques.

In ANCA-associated vasculitis (AAV), both the disease and its treatments contribute to systemic complications, among which, infections represent a major cause of morbidity and mortality. This study aimed to evaluate the prevalence and prognosis of infectious complications in AAV, to identify associated risk factors, and to describe long-term outcomes. This retrospective monocentric study included patients followed in the Nephrology and Internal Medicine departments at Conception Hospital after a first episode or relapse of AAV between 2004 and 2024. Infection was considered if requiring hospitalization or an anti-infectious therapy. Follow-up was conducted until January 1^st, 2025. Among 264 patients included, the incidence of infection was 43.9%, with respiratory infections accounting for 49.1% of cases and bacterial infections for 75.3%, mainly with gram negative bacillus. Infection episodes were significantly associated with age >65 years (p =0.02), hypertension (p=0.04), diabetes (p =0.01), a high Five-Factor Score (p =0.005), a high BVAS (p =0.03), anti-PR3 positivity (p =0.03), acute kidney injury (p=0.004), cyclophosphamide (p =0.05), and intravenous corticosteroid for induction (p =0.03). In multivariate analysis, anti-PR3 positivity (aOR = 2.0, p=0.03) was independent risk factors, whereas methotrexate appeared protective (aOR = 0.08, p=0.001). Infections were independently linked to vasculitis relapses (aOR = 2.8, p=0.007) and cardiovascular events (aOR 3.0, p =0.01). Survival analysis demonstrated a significant association between mortality and infection (HR 2.14 _95%CI[1.59-2.91], p<0.001). Infections are frequent complications in AAV, and exert an independent impact on mortality. Anti-PR3 positivity increases infection risk, whereas methotrexate appears protective.

Patients with chronic kidney disease (CKD) are exposed to high levels of uremic toxins and have an increased risk of cardiovascular disease. Among these toxins, indolic compounds such as indoxyl sulfate (IS) are predictors of cardiovascular events and mortality in CKD patients and induce a procoagulant and proinflammatory vascular phenotype through activation of the aryl hydrocarbon receptor (AhR). Targeting AhR activation by indolic toxins may therefore help prevent cardiovascular complications in CKD. To this end, we investigated in vitro whether natural dietary AhR ligands (galangin, quercetin, curcumin and indole-3-carbinol) could antagonize IS-induced AhR activation and the associated inflammatory response in endothelial cells. The activation of the AhR genomic pathway was assessed by measuring the expression of AhR target genes (CYP1A1, CYP1B1, and AHRR) in endothelial cells and by evaluating AhR-dependent transcriptional activity using a CALUX-AHRE luciferase reporter assay in HG40/6 cells. In parallel, endothelial inflammation was evaluated by analyzing the expression of AhR-related inflammatory genes: F3/tissue factor, PTGS2/COX-2, CCL2/MCP-1, and CXCL8/IL-8. Quercetin was the only ligand capable of antagonizing IS-induced AhR transcriptional activity, as well as the upregulation of the endothelial AhR target genes CYP1A1 and CYP1B1. In contrast, galangin, curcumin, and I3C exhibited no inhibitory effects. Moreover, none of the tested dietary AhR ligands suppressed the IS-induced upregulation of endothelial inflammatory genes; instead, they tended to potentiate IS-induced inflammatory responses at high concentrations. In conclusion, among the AhR ligands tested, quercetin was the only one that attenuated IS-induced activation of the AhR genomic pathway in endothelial cells. However, it may also enhance IS-mediated endothelial inflammation, an effect also observed at specific concentrations of galangin, curcumin, and I3C. These findings suggest that the potential beneficial effects of natural dietary AhR ligands should be carefully considered in the context of CKD patients exhibiting high levels of indolic uremic toxins.

L’hyperkaliémie, fréquente en pratique clinique courante, est un facteur de risque majeur de mortalité. Elle affecte principalement les patients présentant une insuffisance rénale chronique (IRC), un diabète ou recevant un traitement par inhibiteurs du système rénine-angiotensine-aldostérone (iSRAA). La prise en charge thérapeutique a pour objectif non seulement d’éviter les complications de l’hyperkaliémie, mais aussi d’éviter l’arrêt des traitements cardio- et néphroprotecteurs comme les iSRAA. L’emploi du polystyrène sulfonate, largement prescrit, est souvent limité par l’acceptabilité des patients. Des données récentes sont venues mettre en doute son innocuité, notamment sa tolérance digestive. Deux nouvelles molécules échangeuses de potassium ont fait leur apparition, le patiromer et le sulfonate de zirconium. Leur intérêt en pratique clinique ainsi que leur acceptabilité en cas de prescription prolongée, restent à démontrer. L’association d’un diurétique thiazidique ou d’un inhibiteur du cotransporteur sodium-glucose de type 2 (iSGLT2) au traitement par iSRAA dans l’IRC, peut également permettre de mieux contrôler la kaliémie. Il n’existe pas à l’heure actuelle de recommandations pour positionner les différents traitements hypokaliémiants. Le choix de ces traitements doit s’adapter aux pathologies du patient et tenir compte des autres effets attendus de ces molécules. Hyperkalemia is common in everyday clinical practice, and is a major risk factor for mortality. It mainly affects patients with chronic renal failure (CKD), diabetes or receiving treatment with inhibitors of the renin-angiotensin-aldosterone system (iRAAS). Therapeutic management aims not only to avoid the complications of hyperkalemia, but also to avoid discontinuation of cardio- and nephroprotective treatments such as iRAAS. The use of polystyrene sulfonate, widely prescribed, is often limited by patient acceptability. Recent data have cast doubt on its safety, particularly in terms of digestive tolerance. Two new potassium exchange molecules have appeared on the market: patiromer and zirconium sulfonate. Their value in clinical practice, and their acceptability in the event of prolonged prescription, remain to be demonstrated. The combination of a thiazide diuretic or an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) with iRAAS therapy in CKD, may also improve control of kalemia. At present, there are no recommendations for the positioning of the various hypokalemic treatments. The choice of these treatments must be adapted to the patient's pathologies and consider the other expected effects of these molecules.

Background: Medullary sponge kidney (MSK) is characterized by precalyceal dilatation of the renal tubules. This entity is associated with recurrent kidney stone disease (KSD). Although etiopathogenesis is unknown, genetic origin is suspected. Hypothesis: The aim of the study was to describe the variants identified in genes associated with urolithiasis and/or cystic kidney disease in MSK using whole-exome sequencing (WES) in patients diagnosed with MSK. Moreover, one hypothesis supported by the only available genetic cohort study is that MSK is due to disruptions in kidney organogenesis involving the GDNF, RET, or GFRα1 genes. We wanted to test that hypothesis in our population. Methods: WES was performed between January 2023 and June 2024 in 42 patients diagnosed with MSK. The pathogenicity was assessed using American College of Medical Genetics guidelines Positive WES group was defined by one or more “likely pathogenic” or “pathogenic”’ variants in genes associated with monoallelic urolithiasis and/or cystic kidney disease and/or already described in MSK according to the mode of inheritance. We also searched for rare truncating and missense variants in the RET, GDNF, and GFRα1 from a variant datastore which contains unsorted and unfiltered WES results from ∼8000 French patients. We then checked whether the patients identified had an MSK phenotype. Results: Ten patients were identified as WES-positive, involving nine genes: IFT140, PRKCSH, PKHD1, SLC34A3, SLC34A1, SLC26A1, UMOD, COL4A3, and MT-TL1. A total of 140 rare variants of RET (n = 107), GDNF (n = 11), and GFR α1 (n = 22) were identified in the variant datastore, none was associated with MSK. Conclusions: MSK was associated with a diverse set of genes related to KSD and/or cystic kidney diseases that underscore the heterogeneity of MSK, both in its presentation and its underlying genetic basis. MSK may represent a macroscopic phenotype with polygenic origins rather than a distinct entity.