C3 Glomerulonephritis Associated With Unusual IgG4 Antifactor H in IgG4-related Disease.

C3 glomerulonephritis (C3GN) is characterized by glomerular aggression mediated by deregulation of the alternative complement pathway. C3GN can be inherited or consequent to acquired autoantibodies, notably against factor H. We report the case of a patient with systemic active IgG4-related disease who presented for acute kidney injury with glomerular proteinuria and hypocomplementemia related to C3GN associated with IgG4-related interstitial nephritis on kidney biopsy.

Blood-brain barrier permeability in CKD: Link with inflammation and cognitive and mood impairment in rats.

Chronic kidney disease (CKD) is associated with cognitive impairment. CKD is associated with increased permeability of the blood-brain barrier (BBB), resulting in increased cognitive impairment in animals and in humans. The aim of this study is to describe the inflammatory profile in blood and cerebro-spinal fluid (CSF) during a CKD model induced by adenine rich diet (ARD) in rats, in relation to BBB permeability and to explore the cognitive and mood impairment phenotypes.

Uncovering the Link Between Kynurenic Acid Pathway and Kidney Failure.

Introduction: Recent studies have focused on some uremic toxins, particularly those derived from tryptophan, as potential modifiable risk factors of chronic kidney disease (CKD) progression. The kynurenine pathway is the major enzymatic pathway for sequentially catabolizing tryptophan, resulting in key metabolites including kynurenine and kynurenic acid (KA) by the aminoadipate aminotransferase. We aimed at evaluating the association of serum KA levels and KA-to-kynurenine ratio (as indicators of aminoadipate aminotransferase activity) with kidney failure.

Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort.

Introduction: Lumasiran is a drug used in RNA-interference (RNAi) therapy for primary hyperoxaluria type 1 (PH1). Data on its efficacy and safety mainly come from industry-sponsored trials.

Methods: For postmarketing follow-up, French authorities requested a quasi-exhaustive retrospective and prospective study over 5 years for patients receiving lumasiran, requiring the inclusion of at least 90% of patients, named as the DAILY-LUMA cohort (NCT06225882).

Myostatin Exacerbates Endothelial Dysfunction Induced by Uremic Toxin Indoxyl Sulfate and Is Associated with Hemodialysis Arteriovenous Access Complications.

Hemodialysis patients exhibit endothelial dysfunction, contributing to elevated cardiovascular risk and complications of the arteriovenous access. These patients have elevated serum levels of myostatin, a member of the transforming growth factor-β (TGFβ) superfamily, and of the uremic toxin indoxyl sulfate, both of which are pro-inflammatory towards endothelial cells. We hypothesized that myostatin and indoxyl sulfate may synergistically induce endothelial dysfunction by impairing endothelial proliferation and promoting a pro-inflammatory phenotype.

Metabolomics to Identify Unclassified Uremic Toxins: A Comprehensive Literature Review.

A comprehensive review of known uremic retention molecules goes back to more than 10 years ago and did not consider metabolomic analyses. The present analysis searches for as of yet unclassified solutes retained in chronic kidney disease (CKD) by analyzing metabolites associated with relevant outcomes of CKD. This untargeted metabolomics-based approach is compared with a conventional targeted literature search.

Unveiling the role of sex in the metabolism of indoxyl sulfate and apixaban.

Chronic Kidney Disease (CKD) is associated with heightened risk of thrombosis. Prescription of anticoagulants is key to manage it; however, CKD patients have shown an increased risk of bleeding under anticoagulation therapy compared to non-CKD patients. We hypothesized that the sex could modify the metabolism of indoxyl sulfate (IS), a uremic toxin and Apixaban.

Depression in chronic kidney disease: Particularities, specific mechanisms and therapeutic considerations, a narrative review.

Introduction: Depression is highly prevalent during chronic kidney disease (CKD) with studies suggesting prevalence rates ranging from approximately one-quarter to half of CKD patients. CKD and depression have a bidirectional relationship, each disorder aggravating the other, leading to more complex and challenging patient management. Depression during CKD is multifactorial and is associated with increased risk of adverse events and hospitalization.

Phenotypic Heterogeneity of ADTKD-MUC1 Diagnosed Using VNtyper, a Novel Genetic Technique.

Rationale & Objective: Molecular diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to variants in the MUC1 gene has long been challenging because variants lie in a large variable number of tandem repeat (VNTR) region, making identification impossible using standard short-read techniques. Previously, we addressed this diagnostic limitation by developing a computational pipeline named VNtyper for easier reliable detection of MUC1 VNTR pathogenic variants from short-read sequences. This led to unexpected diagnoses of ADTKD-MUC1 among patients with kidney disease referred for genetic testing, which we report here.

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.