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| Open AccessMachine learning-driven virtual biopsy system may increase organ discards at aggressive kidney transplant centers
- Emmanouil Giorgakis
- , Hailey Hardgrave
- & Allison Wells
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Article
| Open AccessNon-invasive in vivo sensing of bacterial implant infection using catalytically-optimised gold nanocluster-loaded liposomes for urinary readout
Implant-associated infections with Staphylococcus aureus pose serious clinical challenges. Here, the authors develop a biosensor based on toxin-responsive liposomes encapsulating gold nanoclusters, providing a non-invasive, colourimetric diagnostic tool for bacterial infection detection with urinary readout.
- Kaili Chen
- , Adrian Najer
- & Molly M. Stevens
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Article
| Open AccessATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice
The involvement of glomerular injury in acute kidney injury (AKI) has not been fully elucidated. Here, authors visualize impaired ATP recovery in podocytes in a murine model of ischemic AKI using intravital ATP imaging and propose accelerated mitochondrial fission as a key factor of ischemic podocyte injury.
- Masahiro Takahashi
- , Shinya Yamamoto
- & Motoko Yanagita
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Article
| Open AccessThe outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients
Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated efficacy in reducing cardiovascular events and potentially improving kidney function in diabetic patients. Here, using the TriNetX platform, the authors show that SGLT-2 inhibitors reduce all-cause mortality and major adverse cardiac and kidney events in diabetic kidney transplant recipients.
- Jia-Yuh Sheu
- , Li-Yang Chang
- & Vin-Cent Wu
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Article
| Open AccessAnalyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline
The authors use longitudinal data from the UK Biobank to search for genetic variants associated with kidney function decline. Using a linear mixed model, they identify 13 independent variants, incl. 6 novel, and link them to genetics of kidney aging.
- Simon Wiegrebe
- , Mathias Gorski
- & Iris M. Heid
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Article
| Open AccessProfiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease
Diabetic kidney disease is the leading cause of kidney failure in the world and cellular insulin resistance is an important driver of this disease. Here, Lay et al identify multiple insulin-resistance driven “common” and “cell-specific” kidney cell pathways and molecules that may be good therapeutic and biomarker targets.
- Abigail C. Lay
- , Van Du T. Tran
- & Matthias Kretzler
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Article
| Open AccessDiscovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan
Here the authors present a large genetic study in East Asians that identifies 97 genetic regions linked to kidney function. These findings aim at better understanding chronic kidney disease in diverse populations.
- Hung-Lin Chen
- , Hsiu-Yin Chiang
- & Chin-Chi Kuo
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Article
| Open AccessCardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study
Despite treatment, patients with chronic kidney disease remain at high risk of kidney failure and cardiovascular disease. Here, the authors show that apelin offers potential cardiorenal protection for this high-risk patient group.
- Fiona A. Chapman
- , Vanessa Melville
- & Neeraj Dhaun
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Article
| Open AccessImmune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis
Antineutrophil cytoplasmic antibody (ANCA) is currently treated with broad-spectrum immune suppressive drugs. Here the authors decipher inflammatory niches in the kidney of patients with ANCA-GN by combining spatial and single-cell transcriptomics to identify ustekinumab as a promising treatment option and successfully treat four ANCA-GN patients.
- Jonas Engesser
- , Robin Khatri
- & Ulf Panzer
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Article
| Open AccessNormothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39
The authors previously reported that normothermic ex vivo kidney perfusion is superior to static cold storage in terms of organ protection, but the detailed mechanism was unclear. Here the authors show that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by administration of AP39, a mitochondria-targeted hydrogen sulfide donor.
- Masataka Kawamura
- , Catherine Parmentier
- & Lisa A. Robinson
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Article
| Open AccessPodocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease
While diabetic kidney disease is characterized by initial glomerular injury, proximal tubule dysfunction determines the progression to kidney fibrosis. Here, the authors show that podocyte KLF6 attenuates proximal tubule injury via ApoJ-CaMK1D signaling in a murine model of diabetic kidney disease.
- Nehaben A. Gujarati
- , Bismark O. Frimpong
- & Sandeep K. Mallipattu
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Article
| Open AccessPlasma proteomics of acute tubular injury
Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment.
- Insa M. Schmidt
- , Aditya L. Surapaneni
- & Sushrut S. Waikar
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Article
| Open AccessGLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been studied for their cardiovascular benefits in type 2 diabetes. Here, the authors show that GLP-1 RAs are associated with reduced mortality and improved cardio-renal outcomes in type 2 diabetes patients with acute kidney disease.
- Heng-Chih Pan
- , Jui-Yi Chen
- & Vin-Cent Wu
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Article
| Open AccessTargeting the transmembrane cytokine co-receptor neuropilin-1 in distal tubules improves renal injury and fibrosis
Many studies have shown that progressive human kidney disease seriously affects the quality of life of patients and may lead to their death. Here, the authors show that targeting of NRP1 represents a promising strategy for the treatment of kidney injury and subsequent chronic kidney disease.
- Yinzheng Li
- , Zheng Wang
- & Rui Zeng
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Article
| Open AccessData-driven prediction of continuous renal replacement therapy survival
Despite decades of use in clinical care, only half of individuals who receive continuous renal replacement therapy (CRRT) benefit, and no consensus exists around who should be placed on CRRT. Here, the authors use electronic health record data from multiple institutions to improve prediction of CRRT response before initiating treatment
- Davina Zamanzadeh
- , Jeffrey Feng
- & Ira Kurtz
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Article
| Open AccessPodocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury
Deubiquitinating of key proteins may be involved in podocyte injury and diabetic kidney disease (DKD). Here, the authors show that OTUD5 in podocytes alleviates DKD through deubiquitinating TAK1 at the K158 site, preventing TAK1 phosphorylation and inflammatory responses in podocytes.
- Ying Zhao
- , Shijie Fan
- & Guang Liang
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Article
| Open AccessLow potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2
The renal epithelium is sensitive to changes in blood K+. Here, Zhang et al. identify low K+ as a potent activator of proximal tubule mTOR/AKT signaling, which occurs through the K+ channel, Kir4.2 to modulate epithelial cell growth and Na+ transport.
- Yahua Zhang
- , Fabian Bock
- & Andrew S. Terker
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Article
| Open AccessCosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction
Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.
- Keith Siew
- , Kevin A. Nestler
- & Stephen B. Walsh
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Article
| Open AccessA cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys
As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.
- Marlon J. A. de Haan
- , Marleen E. Jacobs
- & Ton J. Rabelink
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Article
| Open AccessMultiplexed bulk and single-cell RNA-seq hybrid enables cost-efficient disease modeling with chimeric organoids
IPSC-derived organoids model diseases. Multiplexed coculture and demultiplexing natural genetic barcodes aid in studying genetic effects. Here, authors introduce Vireo-bulk to deconvolve bulk RNA-seq data, quantify donor abundance and identify differentially expressed genes.
- Chen Cheng
- , Gang Wang
- & Jin Zhang
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Article
| Open AccessGlis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Cyst growth in autosomal dominant polycystic kidney disease (ADPKD) is driven by unknown molecular signals that require the presence of intact primary cilia in the absence of the PKD gene products. Here, the authors show that the transcription factor Glis2 is a key effector of this cilia dependent cyst growth pathway and a potential target for therapy in ADPKD
- Chao Zhang
- , Michael Rehman
- & Stefan Somlo
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Article
| Open AccessPD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models.
- John TCHEN
- , Quentin SIMON
- & Nicolas CHARLES
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Article
| Open AccessInhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence
Here the author reveal that histone crotonylation (including H3K9cr) exert a role in kidney fibrosis, where ACSS2 represents a potential target to slow fibrotic kidney disease progression.
- Lingzhi Li
- , Ting Xiang
- & Liang Ma
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Article
| Open AccessEnzymatic conversion of human blood group A kidneys to universal blood group O
ABO blood group compatibility restrictions limit the availability of organs for patients awaiting transplantation. Here, the authors show the rapid enzymatic removal of blood group A antigens from the vasculature of human kidneys using normothermic and hypothermic machine perfusion technologies to make universal blood group O organs for transplantation.
- Serena MacMillan
- , Sarah A. Hosgood
- & Michael L. Nicholson
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Article
| Open AccessNDUFS4 regulates cristae remodeling in diabetic kidney disease
Mitochondrial Ndufs4, a subunit of complex I, is a regulator of the electron transport chain. Here, the authors show that forced expression of Ndufs4 in podocytes improves the assembly of respiratory supercomplexes, maintains cristae integrity, and mitigates the progression of diabetic kidney disease
- Koki Mise
- , Jianyin Long
- & Farhad R. Danesh
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Article
| Open AccessThe proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration
In the kidney, maintaining permeability of the filtration barrier is critical. Here, Sachs W. et al show that homeostasis of podocytes and glomerular endothelial cells relies on differing proteasome constitutions which orchestrate endocytic activity in addition to protein degradation.
- Wiebke Sachs
- , Lukas Blume
- & Catherine Meyer-Schwesinger
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Article
| Open AccessShort-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21
Surgery poses significant risks for patients, with attempts to mitigate these risks using multimodal perioperative care pathways. Here, the authors show that preoperative hypercaloric carbohydrate drinks not only alleviate surgical stress but also demonstrates the replicability of this protection using FGF21 treatment alone.
- Thomas Agius
- , Raffaella Emsley
- & Alban Longchamp
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Article
| Open AccessUnraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development
Kidney disease affects more than 850 million people worldwide, but the development of drug therapeutics has been limited by poor mechanistic understanding. Here, the authors perform epigenome-wide analyses to find methylation changes, and disease mechanisms associated with kidney disease.
- Yu Yan
- , Hongbo Liu
- & Katalin Susztak
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Article
| Open AccessWNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease
Fibroblast heterogeneity is a recognized feature in chronic kidney disease, and although fibrosis is integrant to the pathology, it is lesser known which of the fibroblast populations contribute. Here authors describe a population of proinflammatory fibroblasts, which are found in close proximity to macrophages and may facilitate their recruitment and acquisition of a FOLR2+, pathogenic phenotype.
- Camille Cohen
- , Rana Mhaidly
- & Fatima Mechta-Grigoriou
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Article
| Open AccessX-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases such as chronic kidney disease (CKD). Here, the authors perform a sex-stratified, cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits, with results including identification of four novel loci associated with the CKD-defining trait eGFR.
- Markus Scholz
- , Katrin Horn
- & Cristian Pattaro
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Article
| Open AccessA Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients
Despite being recommended, day-zero biopsies are often not performed, due to the cost and time. Here, the authors show that machine learning and donor’s basic parameters can predict the biopsy, offering a reliable virtual estimation of the day-zero biopsy findings.
- Daniel Yoo
- , Gillian Divard
- & Alexandre Loupy
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Article
| Open AccessThe chromatin landscape of healthy and injured cell types in the human kidney
Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.
- Debora L. Gisch
- , Michelle Brennan
- & Michael T. Eadon
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Article
| Open AccessDeletion of Aurora kinase A prevents the development of polycystic kidney disease in mice
Using different mouse models of Polycystic Kidney Disease, this research demonstrated that deletion of the Aurora Kinase A gene was able to prevent cyst initiation and growth, identifying it as a central regulator of pathogenesis in this condition.
- Ming Shen Tham
- , Denny L. Cottle
- & Ian M. Smyth
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Article
| Open AccessPolygenic risk alters the penetrance of monogenic kidney disease
Polygenic factors may partially explain the observed variability in the penetrance of monogenic diseases. Here, the authors show that a polygenic risk score for chronic kidney disease is significantly associated with a higher risk of renal dysfunction in the two most common monogenic forms of kidney disease, suggesting that accounting for polygenic factors improves risk stratification in monogenic kidney disease.
- Atlas Khan
- , Ning Shang
- & Krzysztof Kiryluk
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Article
| Open AccessChoroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment
In patients with CKD, there is an unmet need for biomarkers that reliably track kidney injury. Here, in a series of prospective studies, the authors show that retinal OCT metrics reflect kidney injury, are modified by treatments for kidney disease and can predict future decline of kidney function.
- Tariq E. Farrah
- , Dan Pugh
- & Neeraj Dhaun
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Article
| Open AccessStrong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.
- Yask Gupta
- , David J. Friedman
- & Simone Sanna-Cherchi
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Article
| Open AccessMicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease
Cisplatin, a chemotherapy drug, can cause long-lasting kidney injury. The authors explore miRNA:mRNA interactions in cisplatin-injured kidneys and find that such a cisplatin inducible miRNA as miR-429-3p suppresses the catabolism of branched-chain amino acids, leading to stimulation of ferroptotic cell death.
- Hisakatsu Sone
- , Tae Jin Lee
- & Sang-Ho Kwon
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Article
| Open AccessAcetyl-CoA is a key molecule for nephron progenitor cell pool maintenance
Cell metabolism plays pivotal roles during kidney embryogenesis. This research shows that glycolysis modulation affects nephron progenitor cells via Acetyl-CoA-modulated pathways, influencing both kidney development, and nephron endowment at birth.
- Fabiola Diniz
- , Nguyen Yen Nhi Ngo
- & Giovane G. Tortelote
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Article
| Open AccessThe extrafollicular B cell response is a hallmark of childhood idiopathic nephrotic syndrome
Although B cell-targeting therapies can provide clinical benefits to children with idiopathic nephrotic syndrome (INS), B lymphocyte subsets have not been extensively studied in this disease. Here, using single-cell RNA sequencing, the authors identify an extrafollicular B cell signature in children with INS.
- Tho-Alfakar Al-Aubodah
- , Lamine Aoudjit
- & Tomoko Takano
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Article
| Open AccessMucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease
Mucosal associated invariant T (MAIT) cells reside in barrier organs, but their contribution to inflammatory processes in the kidneys is not fully known. Here authors find by single cell RNA sequencing that among the different MAIT cell subtypes found at steady state, a population with MAIT17 signature is expanded in both human crescentic glomerulonephritis and its mouse model, and these cells may play protective role in the disease.
- Ann-Christin Gnirck
- , Marie-Sophie Philipp
- & Jan-Eric Turner
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Article
| Open AccessEpidermal growth factor receptor activation is essential for kidney fibrosis development
Fibrosis is the progressive accumulation of excess extracellular matrix produced by myofibroblasts leading to organ failure. Here the authors show that expression of the Epidermal Growth Factor Receptor (EGFR) increases in interstitial myofibroblasts in human and mouse fibrotic kidneys, and selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins.
- Shirong Cao
- , Yu Pan
- & Raymond C. Harris
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Article
| Open AccessPalmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating β-catenin palmitoylation
The role and mechanisms for protein palmitoylation in renal fibrosis remain unclear. Here, the authors show that DHHC9 and APT1 catalysed β-catenin S-palmitoylation on Cys300 contributes to renal fibrosis, which may provide a new therapeutic strategy for chronic kidney diseases.
- Mengru Gu
- , Hanlu Jiang
- & Chunsun Dai
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Article
| Open AccessFibrocystin/Polyductin releases a C-terminal fragment that translocates into mitochondria and suppresses cystogenesis
Fibrocystin/Polyductin (FPC) is a large ciliary membrane protein encoded by PKHD1 which, when mutated, causes ARPKD. Here, the authors show that FPC suppresses cyst development in the kidney of mouse models through the release and mitochondrial translocation of its C terminal product.
- Rebecca V Walker
- , Qin Yao
- & Feng Qian
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Article
| Open AccessMANF stimulates autophagy and restores mitochondrial homeostasis to treat autosomal dominant tubulointerstitial kidney disease in mice
Autosomal dominant tubulointerstitial kidney disease (ADTKD) due to uromodulin mutations is a hereditary kidney disease causing renal fibrosis. Here, the authors show that mesencephalic astrocyte-derived neurotrophic factor can improve defective autophagy/mitophagy and decrease renal scarring in ADTKD.
- Yeawon Kim
- , Chuang Li
- & Ying Maggie Chen
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Article
| Open AccessProteomics of CKD progression in the chronic renal insufficiency cohort
Progression of chronic kidney disease may lead to kidney failure and cardiovascular, metabolic and bone disease complications. Here, the authors conduct a large-scale proteomic study in patients with chronic kidney disease, identify numerous proteins that predict kidney failure, some of which are likely causal mediators and hence potential therapeutic targets.
- Ruth F. Dubin
- , Rajat Deo
- & Peter Ganz
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Article
| Open AccessOmicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease
Here the authors evaluate neutralizing antibodies following COVID-19 bivalent vaccination and find that both Pfizer BA.5 (BNT162b2) and Moderna BA.1 (mRNA-1273) vaccines elicit similar neutralization against Omicron subvariants BA.1, BA.5, BQ.1.1, and XBB.1.5 in patients with end-stage kidney disease.
- Kevin Yau
- , Alexandra Kurtesi
- & Michelle A. Hladunewich
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Article
| Open AccessFeasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes
An implantable bioartificial kidney with a cell-containing bioreactor could be used to treat end-stage renal disease. Here the authors demonstrate the feasibility of an implantable bioreactor by maintaining human cell viability and functionality after implantation in a xenograft model.
- Eun Jung Kim
- , Caressa Chen
- & Shuvo Roy
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Article
| Open AccessAn integrated organoid omics map extends modeling potential of kidney disease
Lassé et al. show that genes involved in kidney organoid proteomic response to TNFα segregate a subset of individuals with poor outcomes in proteinuric kidney disease, demonstrating the relevance of kidney organoid modeling to human kidney disease.
- Moritz Lassé
- , Jamal El Saghir
- & Markus M. Rinschen
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Article
| Open AccessSuPAR mediates viral response proteinuria by rapidly changing podocyte function
Proteinuric kidney diseases are on the rise and have limited treatment options. Here, the authors show soluble urokinase receptor (suPAR) orchestrates viral response proteinuria (VRP) which occurs in response to certain viral infections and podocyte integrin engagement.
- Changli Wei
- , Prasun K. Datta
- & Jochen Reiser