Identification of Renal Transcripts Associated with Kidney Function and Prognosis in ANCA-Associated Vasculitis.

Background: ANCA-associated vasculitis with glomerulonephritis (AAV-GN) frequently progresses to kidney failure. However, tools for risk stratification of kidney outcomes remain limited. Existing approaches inadequately capture the molecular complexity underlying kidney injury, despite its potential value to tailor therapeutic management.

Diagnostic Value of Biological Parameters in Biopsy-Confirmed Thrombotic Microangiopathy-MATRIX Consortium Group.

Introduction: The diagnosis of thrombotic microangiopathy (TMA) relies on common biological parameters, the diagnostic value of which are unknown.

Methods: The presence of common biological parameters was assessed in 967 patients with TMA from 2009 to 2023 (ClinicalTrials.gov: NCT05991245).

Pulmonary-renal syndrome under Dostarlimab, a recent PD-1 inhibitor, in a patient with Endometrial Cancer.

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various cancers since 2011. Dostarlimab is a recent anti-PD-1 agent, approved notably as a first-line treatment for endometrial cancer. The renal toxicity of anti-PD-1 agents is rare, with a prevalence ranging from 1 to 5% depending on the studies, mainly manifesting as acute interstitial nephritis and, much more rarely, as glomerulopathies.

Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant gene panel: A multicenter international study.

Transcriptomic analysis of kidney biopsies has demonstrated the potential to improve diagnosis of allograft rejection. Here, we developed a molecular assessment of antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR) based on the Banff Human Organ Transplant consensus gene panel. Expression assays of formalin-fixed paraffin-embedded kidney biopsies from well-phenotyped cohorts were used to develop prediction models for AMR and TCMR and an automated report of gene expression-based diagnosis.

Resolution of Metabolic Dysfunction-associated Steatohepatitis With No Worsening of Fibrosis After Bariatric Surgery Improves 15-year Survival: A Prospective Cohort Study.

Background & Aims: The aim of this study was to investigate the consequences of the histological progression of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis on long-term survival after bariatric surgery.

Methods: From 1994 to 2021, 3028 patients at the University Hospital of Lille were prospectively included. Baseline liver biopsies were systematically performed with proposed follow-up biopsies 1 year after surgery, mainly in patients with MASH.

Severe hypophosphatemia induced by excessive production of FGF23 in acute hepatitis: from bedside to bench.

Background: Although hepatic production of FGF23 has been suggested in chronic settings, there are no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression.

Methods: Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively ( hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared with controls of hepatic fibrosis or healthy liver.

Pregnancy as a susceptible state for thrombotic microangiopathies.

Pregnancy and the postpartum period represent phases of heightened vulnerability to thrombotic microangiopathies (TMAs), as evidenced by distinct patterns of pregnancy-specific TMAs (e.g., preeclampsia, HELLP syndrome), as well as a higher incidence of nonspecific TMAs, such as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, during pregnancy.

A predictive mortality score in ANCA-associated renal vasculitis.

Background: Several scores have been developed to predict mortality at anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none has been developed in this specific population. We aimed to propose a novel and more accurate score specific for them.

Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery.

Background & Aims: The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery.

Methods: Participants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60 months after surgery.

Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.

Background & Aims: Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and clock disruption increases susceptibility to MASLD progression in rodent models. We therefore investigated whether the time-of-day-dependent transcriptome and metabolome are significantly altered in human steatotic and MASH livers.

Combining diabetes, sex, and menopause as meaningful clinical features associated with NASH and liver fibrosis in individuals with class II and III obesity: A retrospective cohort study.

Objective: Steatotic liver disease (SLD) is frequent in individuals with obesity. In this study, type 2 diabetes (T2D), sex, and menopausal status were combined to refine the stratification of obesity regarding the risk of advanced SLD and gain further insight into disease physiopathology.

Methods: This study enrolled 1446 participants with obesity from the ABOS cohort (NCT01129297), who underwent extensive phenotyping, including liver histology and transcriptome profiling.

Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab-bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study.

Background: Clinical benefits of atezolizumab plus bevacizumab (atezolizumab-bevacizumab) are observed only in a subset of patients with hepatocellular carcinoma and the development of biomarkers is needed to improve therapeutic strategies. The atezolizumab-bevacizumab response signature (ABRS), assessed by molecular biology profiling techniques, has been shown to be associated with progression-free survival after treatment initiation. The primary objective of our study was to develop an artificial intelligence (AI) model able to estimate ABRS expression directly from histological slides, and to evaluate if model predictions were associated with progression-free survival.

Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies.

The complement system plays a key role in the pathophysiology of kidney thrombotic microangiopathies (TMA), as illustrated by atypical hemolytic uremic syndrome. But complement abnormalities are not the only drivers of TMA lesions. Among other potential pathophysiological actors, we hypothesized that alteration of heparan sulfate (HS) in the endothelial glycocalyx could be important.

Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity.

Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis.

Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.

Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy.

Background: Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN.

Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages.

Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation.

Early Renal Recovery after the First Flare of Pauci-Immune Glomerulonephritis.

Introduction: Renal involvement is a severe manifestation of antineutrophil cytoplasmic antibody-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after the first flare has seldom been studied.