Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease.

Cardiovascular disease (CVD) is a major complication of chronic kidney disease (CKD), despite improvements in patient care. Vascular inflammation is a crucial process in the pathogenesis of CVD and a critical factor in the cardiovascular complications in CKD patients. CKD promotes a pro-inflammatory environment that impacts the vascular wall, leading to endothelial dysfunction, increased oxidative stress, and vascular remodeling.

[Acute kidney injury in cancer patients receiving immune checkpoint inhibitor therapy-shared guidelines of FITC/SFNDT].

Cancer treatments have been dramatically modified by the introduction and the development of immunological checkpoint inhibitors (ICI). These treatments have many side effects, including acute kidney injury (AKI). Their combination with other treatments makes the diagnosis complex.

New insights into mechanisms underlying cognitive impairment in chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. Patients with CKD display an increased permeability of the blood-brain barrier. Zimmermann et al.

Increased Blood-Brain Barrier Permeability and Cognitive Impairment in Patients With ESKD.

Introduction: Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. This cognitive impairment is associated with an increased permeability of blood-brain barrier (BBB) in rodents with CKD, linked to activation of aryl hydrocarbon receptor (AhR) by indoxyl sulphate (IS). The objective of the BREIN study was to confirm the increased BBB permeability in humans with CKD.

Prospective Multicenter Study on Early Proximal Tubular Injury in COVID-19-Related Acute Respiratory Distress Syndrome.

Introduction: During COVID-19, renal impairment is associated with poor prognosis in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS).

Methods: In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation (MV) for ARDS were enrolled in 3 ICUs.

Acute and Chronic Kidney Dysfunction and Prognosis following Thrombectomy for Ischemic Stroke.

Introduction: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy.

Methods: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy.

Beyond the kidney biopsy: genomic approach to undetermined kidney diseases.

Background: According to data from large national registries, almost 20%-25% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate.

Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis.

Introduction: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD).

Methods: ES was proposed during routine clinical care in patients with UKD from January 2020 to December 2021.

Weaning Maintenance Therapy in Lupus Nephritis: For Whom, When, and How?

Lupus nephritis (LN) is one of the main determinants of the severity of systemic lupus erythematosus (SLE). LN flares can lead to organ damage with chronic kidney disease (CKD) or even end-stage kidney disease (ESKD) and impair patients' survival. The "treat-to-target" strategy, which aims at obtaining and maintaining remission or low disease activity of SLE to alleviate symptoms and prevent organ damage, also refers to the control of residual activity in the kidney.

Impact of reference panel composition on scores of script concordance test assessing basic nephrology knowledge in undergraduate medical education.

Purpose: In the assessment of basic medical knowledge, the composition of the reference panel between specialists and primary care (PC) physicians is a contentious issue. We assessed the effect of panel composition on the scores of undergraduate medical students in a script concordance test (SCT).

Methods: The scale of an SCT on basic nephrology knowledge was set by a panel of nephrologists or a mixed panel of nephrologists and PC physicians.

VNtyper enables accurate alignment-free genotyping of coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease.

The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease- (ADTKD-) is caused by specific frameshift variants in the coding VNTR of the gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability.

Indoxyl sulfate inhibits muscle cell differentiation via Myf6/MRF4 and MYH2 downregulation.

Background: Chronic kidney disease (CKD) is associated with a significant decrease in muscle strength and mass, possibly related to muscle cell damage by uremic toxins. Here, we studied in vitro and in vivo the effect of indoxyl sulfate (IS), an indolic uremic toxin, on myoblast proliferation, differentiation and expression of myogenic regulatory factors (MRF)-myoblast determination protein 1 (MyoD1), myogenin (Myog), Myogenic Factor 5 (Myf5) and myogenic regulatory factor 4 (Myf6/MRF4)-and expression of myosin heavy chain, Myh2.

Methods: C2C12 myoblasts were cultured in vitro and differentiated in myotubes for 7 days in the presence of IS at a uremic concentration of 200 µM.

Systematic Comparison of Uremic Toxin Removal Using Different Hemodialysis Modes: A Single-Center Crossover Prospective Observational Study.

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group.

Kidney disease and stroke: epidemiology and potential mechanisms of susceptibility.

Patients with chronic kidney disease (CKD) have an increased risk of both ischaemic and haemorrhagic stroke compared with the general population. Both acute and chronic kidney impairment are independently associated with poor outcome after the onset of a stroke, after adjustment for confounders. End-stage kidney disease (ESKD) is associated with a 7- and 9-fold increased incidence of both ischaemic and haemorrhagic strokes, respectively, poorer neurological outcome and a 3-fold higher mortality.

Stability Study of Parenteral N-Acetylcysteine, and Chemical Inhibition of Its Dimerization.

Parenteral N-acetylcysteine has a wide variety of clinical applications, but its use can be limited by a poor chemical stability. We managed to control parenteral N-acetylcysteine stability, and to study the influence of additives on the decrease of N-acetylcysteine degradation. First, an HPLC-UV dosing method of N-acetylcysteine and its main degradation product, a dimer, was validated and the stability without additive was studied.

Rheopheresis Performed in Hemodialysis Patients Targets Endothelium and Has an Acute Anti-Inflammatory Effect.

Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) patients with severe microischemia. Interestingly, some studies showed that rheopheresis sessions improve endothelial function.

Protein/Fiber Index Modulates Uremic Toxin Concentrations in Hemodialysis Patients.

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), two uremic toxins (UTs), are associated with increased mortality in patients with chronic kidney disease (CKD). These toxins are produced by the microbiota from the diet and excreted by the kidney. The purpose of this study was to analyze the effect of diet on IS and PCS concentration in hemodialysis (HD) patients.

Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19.

Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020.

Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial.

Objectives: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown.

Mechanisms of myostatin and activin A accumulation in chronic kidney disease.

Background: Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance.

Methods: We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR).

What If Not All Metabolites from the Uremic Toxin Generating Pathways Are Toxic? A Hypothesis.

The topic of uremic toxicity has received broad attention from the nephrological community over the past few decades. An aspect that is much less often considered is the possibility that the metabolic pathways that generate uremic toxins also may produce molecules that benefit body functions. Here, we discuss this dualism based on the example of tryptophan-derived metabolites, which comprise elements that are mainly toxic, such as indoxyl sulfate, kynurenine and kynurenic acid, but also beneficial compounds, such as indole, melatonin and indole-3-propionic acid, and ambivalent (beneficial for some aspects and harmful for others) compounds such as serotonin.