Proteinuria and tubular cells: Plasticity and toxicity.

Aim: Proteinuria is the most robust predictive factors for the progression of chronic kidney disease (CKD), and interventions targeting proteinuria reduction have shown to be the most effective nephroprotective treatments to date. While glomerular dysfunction is the primary source of proteinuria, its consequences extend beyond the glomerulus and have a profound impact on tubular epithelial cells. Indeed, proteinuria induces notable phenotypic changes in tubular epithelial cells and plays a crucial role in driving CKD progression.

Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria.

Key Points: Glomerular proteinuria induces large-scale changes in gene expression along the nephron. Increased protein uptake in the proximal tubule results in axial remodeling and injury. Increased protein delivery to the distal tubule causes dedifferentiation of the epithelium.

The role of hypoxia in chronic kidney disease: a nuanced perspective.

Purpose Of Review: This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease.

Recent Findings: Emerging evidence challenges the traditional view that hypoxia is universally harmful in CKD context.

A transfer learning framework to elucidate the clinical relevance of altered proximal tubule cell states in kidney disease.

The application of single-cell technologies in clinical nephrology remains elusive. We generated an atlas of transcriptionally defined cell types and cell states of human kidney disease by integrating single-cell signatures reported in the literature with newly generated signatures obtained from 5 patients with acute kidney injury. We used this information to develop kidney-specific cell-level information ExtractoR (K-CLIER), a transfer learning approach specifically tailored to evaluate the role of cell types/states on bulk RNAseq data.

Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21.

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking.

NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing.

Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix (ECM) and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer.

Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased.

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population.

Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease.

Introduction: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.

Methods: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction.

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function.

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease.

Tubular Cell Glucose Metabolism Shift During Acute and Chronic Injuries.

Acute and chronic kidney disease are responsible for large healthcare costs worldwide. During injury, kidney metabolism undergoes profound modifications in order to adapt to oxygen and nutrient shortage. Several studies highlighted recently the importance of these metabolic adaptations in acute as well as in chronic phases of renal disease, with a potential deleterious effect on fibrosis progression.

Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis.

Objectives: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed.

Hypoxia in chronic kidney disease: towards a paradigm shift?

Chronic kidney disease (CKD) is defined as an alteration of kidney structure and/or function lasting for >3 months [1]. CKD affects 10% of the general adult population and is responsible for large healthcare costs [2]. Since the end of the last century, the role of hypoxia in CKD progression has controversially been discussed.

Kinetic GFR Outperforms CKD-EPI for Slow Graft Function Prediction in the Immediate Postoperative Period Following Kidney Transplantation.

Background: Rapid identification of patients at high risk for slow graft function (SGF) is of major importance in the immediate period following renal graft transplantation, both for early therapeutic decisions and long-term prognosis. Due to the high variability of serum creatinine levels after surgery, glomerular filtration rate (GFR) estimation is challenging. In this situation, kinetic estimated GFR (KeGFR) equations are interesting tools but have never been assessed for the identification of SGF patients.

Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism.

Glucose levels are tightly regulated at all times. Gluconeogenesis is the metabolic pathway dedicated to glucose synthesis from non-hexose precursors. Gluconeogenesis is critical for glucose homoeostasis, particularly during fasting or stress conditions.

Author Correction: Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown.

Tubular NOX4 expression decreases in chronic kidney disease but does not modify fibrosis evolution.

Background: NADPH oxidase 4 (NOX4) catalyzes the formation of hydrogen peroxide (HO). NOX4 is highly expressed in the kidney, but its role in renal injury is unclear and may depend on its specific tissue localization.

Methods: We performed immunostaining with a specific anti-NOX4 antibody and measured NOX4 mRNA expression in human renal biopsies encompassing diverse renal diseases.

Experimental Model of Human Malignant Mesothelioma in Athymic Mice.

Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by asbestos exposure, which is difficult to diagnose and treat. Here, we characterized an in vivo orthotopic xenograft model consisting of human mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor injected in partially immunodeficient athymic mice. We assessed tumor formation and tumor-dependent patterns of inflammation.