Featured
-
-
Article
| Open Access
Enzymatic 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
-
Article
| Open Access
NDUFS4 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
-
Article
| Open Access
The 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
-
Article
| Open Access
Short-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
-
Article
| Open Access
Unraveling 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
-
Article
| Open Access
WNT-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
-
Article
| Open Access
X-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
-
Article
| Open Access
A 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
-
Article
| Open Access
The 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
-
Article
| Open Access
Deletion 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
-
Article
| Open Access
Polygenic 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
-
Article
| Open Access
Choroidal 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
-
Article
| Open Access
Strong 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
-
Article
| Open Access
MicroRNA-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
-
Article
| Open Access
Acetyl-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
-
Article
| Open Access
The 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
-
Article
| Open Access
Mucosal-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
-
Article
| Open Access
Epidermal 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
-
Article
| Open Access
Palmitoyltransferase 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
-
Article
| Open Access
Fibrocystin/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
-
Article
| Open Access
MANF 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
-
Article
| Open Access
Proteomics 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
-
Article
| Open Access
Omicron 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
-
Article
| Open Access
Feasibility 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
-
Article
| Open Access
An 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
-
Article
| Open Access
SuPAR 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
-
Article
| Open Access
Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron
The mechanisms of failed tubule repair after acute kidney injury are incompletely understood. Here, the authors show spatial and temporal analysis of cycling cells relative to initial necrosis and postulate pronounced injury expansion into non-necrotic tissue regions, predictive of tubule atrophy.
- Luca Bordoni
- , Anders M. Kristensen
- & Ina Maria Schiessl
-
Article
| Open Access
Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
Although long-term kidney allograft failure is broadly classified as T cell- or antibody-mediated, this dichotomy is not always apparent in all patients, highlighting the need for improved allograft tissue characterisation. Here, the authors use single-cell RNA sequencing and multiplex imaging for transcriptomic and spatial profiling of allograft tissue from patients experiencing different degrees of rejection severity.
- Baptiste Lamarthée
- , Jasper Callemeyn
- & Maarten Naesens
-
Article
| Open Access
A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease
Kidney stone disease causes significant morbidity and increases in health care utilization. Here, the authors define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human renal papilla and identify associated urinary biomarkers.
- Victor Hugo Canela
- , William S. Bowen
- & Tarek M. El-Achkar
-
Article
| Open Access
HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
The authors previously reported HCK was associated with kidney inflammation and fibrosis. Here, they further unravel a mechanism of HCK regulating autophagy within macrophages, altering their polarization, proliferation, and migration and they also developed a more selective HCK inhibitor.
- Man Chen
- , Madhav C. Menon
- & Chengguo Wei
-
Article
| Open Access
A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury
KIM1 is dramatically upregulated in acute kidney injury (AKI) and but how KIM1 affects AKI remains unknown. Here, the authors report that renal specific Kim1 knockout relieves AKI, unveil a YY1-KIM1-DR5 axis in the progression of AKI, and suggest potential therapeutic strategies against AKI.
- Chen Yang
- , Huidie Xu
- & Ling Zheng
-
Article
| Open Access
Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent
Current clinical methods for assessing kidney function report an aggregate value for both kidneys, and lack the ability to say which kidney is dysfunctioning or even to localize the dysfunction to a region of renal pathology. Here, the authors show that an injectable dye can be used to map kidney function by magnetic resonance imaging, offering a safer alternative than existing dyes for the spatial evaluation of kidney health.
- Nicholas D. Calvert
- , Alexia Kirby
- & Adam J. Shuhendler
-
Article
| Open Access
Predicting in-hospital outcomes of patients with acute kidney injury
Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. Here, the authors show a deep learning model that can identify patients with acute kidney injury (AKI) who are at high risk of death or dialysis at certain time points.
- Changwei Wu
- , Yun Zhang
- & Guisen Li
-
Article
| Open Access
Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation
Porcine kidney xenotransplantation is accelerating towards clinical testing. Here the authors present preclinical results examining xenograft growth and participation in renal endocrine pathways that can be used to inform clinical study design.
- Daniel J. Firl
- , Grace Lassiter
- & Katherine C. Hall
-
Article
| Open Access
Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model
The possibility of banking cryopreserved organs could make transplantation medicine much more accessible. Here, the authors show that vitrification and nanowarming—cooling organs to an ice-free state followed by rapid rewarming using nanoparticles and magnetic fields—enables organ cryopreservation, long-term banking, and recovery of full function in a rat kidney transplant model.
- Zonghu Han
- , Joseph Sushil Rao
- & Erik B. Finger
-
Article
| Open Access
Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease
Chronic kidney disease (CKD) is a disease that irreversibly leads to loss of renal function. Here, the authors demonstrate the beneficial effect of intrinsic TGF-b signaling on mitochondrial function and inflammation in the proximal tubule epithelium in response to kidney injury.
- Merve Kayhan
- , Judith Vouillamoz
- & Stellor Nlandu Khodo
-
Article
| Open Access
A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology
The human genome still contains numerous uncharacterized genes. Here, the authors identify a fast evolving Factor associated with Metabolism and Energy (FAME) that is associated with altered body weight, energy expenditure, and metabolism and study its function in knockout mouse models.
- Julian Petersen
- , Lukas Englmaier
- & Igor Adameyko
-
Article
| Open Access
The AE4 transporter mediates kidney acid-base sensing
Maintaining systemic acid-base balance is a central task of the kidneys, but it is still undetermined how acid-base alterations are perceived by the kidney. Here, the authors show that the solute transporter AE4 in β-intercalated cells is an essential part of the renal acid-base sensing mechanism
- H. Vitzthum
- , M. Koch
- & H. Ehmke
-
Article
| Open Access
HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice
Although accumulating evidence indicates that epithelial cell cycle G2/M arrest is involved in kidney fibrosis, the underlying mechanism remains unclear. Here, the authors show that HDAC9 is upregulated in the fibrotic kidney and promotes epithelial cell cycle arrest in G2/M by regulating STAT1.
- Yang Zhang
- , Yujie Yang
- & Fan Yi
-
Article
| Open Access
A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes
In a multicenter randomized trial, researchers found that electronic alerts increased the rate of discontinuation of potential nephrotoxins. This did not translate into improved clinical outcomes, except among those exposed to proton-pump inhibitors.
- F. Perry Wilson
- , Yu Yamamoto
- & Ugochukwu Ugwuowo
-
Article
| Open Access
Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome
Here, the authors have performed a multi-population GWAS meta-analysis of pediatric steroid sensitive nephrotic syndrome cases to discover 12 loci (4 novel), fine-map HLA, implicate kidney and immune factors, and associate the polygenic risk score with earlier disease onset.
- Alexandra Barry
- , Michelle T. McNulty
- & Matthew G. Sampson
-
Article
| Open Access
Isthmin-1 (Ism1) modulates renal branching morphogenesis and mesenchyme condensation during early kidney development
Loss of Ism1 in mice results in kidney agenesis and dysplasia that are common human diseases. Here they show that Ism1 is expressed in metanephric mesenchyme and acts as a ligand of Integrin α8β1 to regulate mesenchyme condensation during early renal branching morphogenesis.
- Ge Gao
- , Xiaoping Li
- & Zhongjun Zhou
-
Article
| Open Access
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Mutations in the gene encoding PC1 cause ADPKD, a common genetic renal disease. Here, the authors show that expression of the C-terminal 200 amino acids of the large PC1 protein in mouse models of ADPKD suppresses cystic disease through an interaction with the mitochondrial enzyme NNT.
- Laura Onuchic
- , Valeria Padovano
- & Michael J. Caplan
-
Article
| Open Access
Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy
Immune checkpoint inhibitors (ICI) may have unanticipated side effects in transplant recipients who subsequently develop tumors. Here the authors used single-cell sequencing to identify and characterize allogeneic reactive T cells that developed after an ICI course for melanoma in a transplant recipient.
- Garrett S. Dunlap
- , Daniel DiToro
- & Deepak A. Rao
-
Article
| Open Access
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice
Kidney injury leads to fibrosis during the progression of chronic kidney disease. Here the authors report that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in a study with male mice, potentially via TAF7/RAPTOR/mTORC1 signaling.
- Yunwen Yang
- , Suwen Liu
- & Aihua Zhang
-
Article
| Open Access
Imputation-powered whole-exome analysis identifies genes associated with kidney function and disease in the UK Biobank
An exome wide association study of UK Biobank data revealed 158 variants and 105 genes significantly associated with kidney function traits and disease. The findings are supported by functional evidence for a previously unreported mutation in CLDN10.
- Matthias Wuttke
- , Eva König
- & Christian Fuchsberger
-
Article
| Open Access
Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment
m6A modification has been reported to play roles in many developmental and pathological processes, but its role in AKI remains poorly understood. Here, the authors show the role and the mechanism of the m6A demethylase, ALKBH5 on IRI induced AKI.
- Juntao Chen
- , Cuidi Xu
- & Tongyu Zhu
-
Article
| Open Access
Next-Generation Morphometry for pathomics-data mining in histopathology
Pathology diagnostics still rely on tissue morphology assessment by trained experts. Here, the authors perform deep-learning-based segmentation followed by large-scale feature extraction of histological images, i.e., next-generation morphometry, to enable outcome-relevant and disease-specific pathomics analysis of non-tumor kidney pathology.
- David L. Hölscher
- , Nassim Bouteldja
- & Peter Boor
-
Article
| Open Access
The classical pathway triggers pathogenic complement activation in membranous nephropathy
It is generally thought that complement activation in human membranous nephropathy (MN) occurs predominantly via the lectin or alternative pathway. Here, the authors show that the classical pathway is the dominant form of complement activation in MN and a pathogenic driver of the disease.
- Larissa Seifert
- , Gunther Zahner
- & Nicola M. Tomas
Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence