Nephrology

  • Article | | open

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    • , Makoto Sanbo
    • , Hideki Masaki
    • , Hideyuki Sato
    • , Tomoyuki Yamaguchi
    • , Shinichi Hochi
    • , Toshihiro Kobayashi
    • , Hiromitsu Nakauchi
    •  & Masumi Hirabayashi
  • Article | | open

    Glycogen Synthase Kinase 3 (GSK3) has conserved functions across species but its role in the kidney is unclear. Here, the authors show that in the kidney podocyte cell of mice and related nephrocyte in Drosophila that GSK3 is a master regulator of function both during development and in maturity.

    • J. A. Hurcombe
    • , P. Hartley
    • , A. C. Lay
    • , L. Ni
    • , J. J. Bedford
    • , J. P. Leader
    • , S. Singh
    • , A. Murphy
    • , C. L. Scudamore
    • , E. Marquez
    • , A. F. Barrington
    • , V. Pinto
    • , M. Marchetti
    • , L.-F. Wong
    • , J. Uney
    • , M. A. Saleem
    • , P. W. Mathieson
    • , S. Patel
    • , R. J. Walker
    • , J. R. Woodgett
    • , S. E. Quaggin
    • , G. I. Welsh
    •  & R. J. M. Coward
  • Article | | open

    Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.

    • Alena V. Yermalovich
    • , Jihan K. Osborne
    • , Patricia Sousa
    • , Areum Han
    • , Melissa A. Kinney
    • , Michael J. Chen
    • , Daisy A. Robinton
    • , Helen Montie
    • , Dan S. Pearson
    • , Sean B. Wilson
    • , Alexander N. Combes
    • , Melissa H. Little
    •  & George Q. Daley
  • Article | | open

    Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.

    • Andrew P. Morris
    • , Thu H. Le
    • , Haojia Wu
    • , Artur Akbarov
    • , Peter J. van der Most
    • , Gibran Hemani
    • , George Davey Smith
    • , Anubha Mahajan
    • , Kyle J. Gaulton
    • , Girish N. Nadkarni
    • , Adan Valladares-Salgado
    • , Niels Wacher-Rodarte
    • , Josyf C. Mychaleckyj
    • , Nicole D. Dueker
    • , Xiuqing Guo
    • , Yang Hai
    • , Jeffrey Haessler
    • , Yoichiro Kamatani
    • , Adrienne M. Stilp
    • , Gu Zhu
    • , James P. Cook
    • , Johan Ärnlöv
    • , Susan H. Blanton
    • , Martin H. de Borst
    • , Erwin P. Bottinger
    • , Thomas A. Buchanan
    • , Sylvia Cechova
    • , Fadi J. Charchar
    • , Pei-Lun Chu
    • , Jeffrey Damman
    • , James Eales
    • , Ali G. Gharavi
    • , Vilmantas Giedraitis
    • , Andrew C. Heath
    • , Eli Ipp
    • , Krzysztof Kiryluk
    • , Holly J. Kramer
    • , Michiaki Kubo
    • , Anders Larsson
    • , Cecilia M. Lindgren
    • , Yingchang Lu
    • , Pamela A. F. Madden
    • , Grant W. Montgomery
    • , George J. Papanicolaou
    • , Leslie J. Raffel
    • , Ralph L. Sacco
    • , Elena Sanchez
    • , Holger Stark
    • , Johan Sundstrom
    • , Kent D. Taylor
    • , Anny H. Xiang
    • , Aleksandra Zivkovic
    • , Lars Lind
    • , Erik Ingelsson
    • , Nicholas G. Martin
    • , John B. Whitfield
    • , Jianwen Cai
    • , Cathy C. Laurie
    • , Yukinori Okada
    • , Koichi Matsuda
    • , Charles Kooperberg
    • , Yii-Der Ida Chen
    • , Tatjana Rundek
    • , Stephen S. Rich
    • , Ruth J. F. Loos
    • , Esteban J. Parra
    • , Miguel Cruz
    • , Jerome I. Rotter
    • , Harold Snieder
    • , Maciej Tomaszewski
    • , Benjamin D. Humphreys
    •  & Nora Franceschini
  • Article | | open

    There are currently no effective therapies available for acute kidney injury (AKI). Here the authors generate molybdenum-based polyoxometalate nanoclusters and show that these have preferential renal uptake and can ameliorate AKI pathology in mice by scavenging reactive oxygen species.

    • Dalong Ni
    • , Dawei Jiang
    • , Christopher J. Kutyreff
    • , Jianhao Lai
    • , Yongjun Yan
    • , Todd E. Barnhart
    • , Bo Yu
    • , Hyung-Jun Im
    • , Lei Kang
    • , Steve Y. Cho
    • , Zhaofei Liu
    • , Peng Huang
    • , Jonathan W. Engle
    •  & Weibo Cai
  • Article | | open

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    • , Mette Madsen
    • , Karsten Skjødt
    • , Søren Kragh Moestrup
    •  & Christian Brix Folsted Andersen
  • Article | | open

    The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.

    • Xiaoguang Xu
    • , James M. Eales
    • , Artur Akbarov
    • , Hui Guo
    • , Lorenz Becker
    • , David Talavera
    • , Fehzan Ashraf
    • , Jabran Nawaz
    • , Sanjeev Pramanik
    • , John Bowes
    • , Xiao Jiang
    • , John Dormer
    • , Matthew Denniff
    • , Andrzej Antczak
    • , Monika Szulinska
    • , Ingrid Wise
    • , Priscilla R. Prestes
    • , Maciej Glyda
    • , Pawel Bogdanski
    • , Ewa Zukowska-Szczechowska
    • , Carlo Berzuini
    • , Adrian S. Woolf
    • , Nilesh J. Samani
    • , Fadi J. Charchar
    •  & Maciej Tomaszewski
  • Article | | open

    Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

    • Adrienne Tin
    • , Yong Li
    • , Jennifer A. Brody
    • , Teresa Nutile
    • , Audrey Y. Chu
    • , Jennifer E. Huffman
    • , Qiong Yang
    • , Ming-Huei Chen
    • , Cassianne Robinson-Cohen
    • , Aurélien Macé
    • , Jun Liu
    • , Ayşe Demirkan
    • , Rossella Sorice
    • , Sanaz Sedaghat
    • , Melody Swen
    • , Bing Yu
    • , Sahar Ghasemi
    • , Alexanda Teumer
    • , Peter Vollenweider
    • , Marina Ciullo
    • , Meng Li
    • , André G. Uitterlinden
    • , Robert Kraaij
    • , Najaf Amin
    • , Jeroen van Rooij
    • , Zoltán Kutalik
    • , Abbas Dehghan
    • , Barbara McKnight
    • , Cornelia M. van Duijn
    • , Alanna Morrison
    • , Bruce M. Psaty
    • , Eric Boerwinkle
    • , Caroline S. Fox
    • , Owen M. Woodward
    •  & Anna Köttgen
  • Article | | open

    Injuries in the embryonal kidney can be repaired by a cell migratory response but how this is regulated at a molecular level is unclear. Here, the authors show in mice that deletion of Cxcl12 and Myc delays pronephros injury repair by changing mitochondrial metabolism and glycolysis.

    • Toma A. Yakulov
    • , Abhijeet P. Todkar
    • , Krasimir Slanchev
    • , Johannes Wiegel
    • , Alexandra Bona
    • , Martin Groß
    • , Alexander Scholz
    • , Isabell Hess
    • , Anne Wurditsch
    • , Florian Grahammer
    • , Tobias B. Huber
    • , Virginie Lecaudey
    • , Tillmann Bork
    • , Jochen Hochrein
    • , Melanie Boerries
    • , Justine Leenders
    • , Pascal de Tullio
    • , François Jouret
    • , Albrecht Kramer-Zucker
    •  & Gerd Walz
  • Article | | open

    Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.

    • Xingbo Xu
    • , Xiaoying Tan
    • , Björn Tampe
    • , Tim Wilhelmi
    • , Melanie S. Hulshoff
    • , Shoji Saito
    • , Tobias Moser
    • , Raghu Kalluri
    • , Gerd Hasenfuss
    • , Elisabeth M. Zeisberg
    •  & Michael Zeisberg
  • Article | | open

    Adaptor for IL-17 receptors (Act1) is known to be crucial for IL-17-mediated immune responses. Here the authors show that Act1 also functions as a negative regulator of T and B cells by direct inhibition of STAT3.

    • Cun-Jin Zhang
    • , Chenhui Wang
    • , Meiling Jiang
    • , Chunfang Gu
    • , Jianxin Xiao
    • , Xing Chen
    • , Bradley N. Martin
    • , Fangqiang Tang
    • , Erin Yamamoto
    • , Yibo Xian
    • , Han Wang
    • , Fengling Li
    • , R. Balfour Sartor
    • , Howard Smith
    • , M. Elaine Husni
    • , Fu-Dong Shi
    • , Ji Gao
    • , Julie Carman
    • , Ashok Dongre
    • , Susan C. McKarns
    • , Ken Coppieters
    • , Trine N. Jørgensen
    • , Warren J. Leonard
    •  & Xiaoxia Li
  • Article | | open

    Mutations in the cation channel PKD2 cause human autosomal dominant polycystic kidney disease but its channel function and gating mechanism are poorly understood. Here authors study PKD2 using electrophysiology and cryo-EM, which identifies hydrophobic gates and proposes a gating mechanism for PKD2.

    • Wang Zheng
    • , Xiaoyong Yang
    • , Ruikun Hu
    • , Ruiqi Cai
    • , Laura Hofmann
    • , Zhifei Wang
    • , Qiaolin Hu
    • , Xiong Liu
    • , David Bulkey
    • , Yong Yu
    • , Jingfeng Tang
    • , Veit Flockerzi
    • , Ying Cao
    • , Erhu Cao
    •  & Xing-Zhen Chen
  • Article | | open

    Patients suffering from congenital nephrogenic diabetes insipidus (NDI) fail to concentrate urine due to mutations in vasopressin type 2 receptor (V2R). Here Ando et al. show that agents disrupting the interaction between PKA and AKAPs restore aquaporin-2 activity downstream of V2R, offering a therapeutic approach for the treatment of NDI.

    • Fumiaki Ando
    • , Shuichi Mori
    • , Naofumi Yui
    • , Tetsuji Morimoto
    • , Naohiro Nomura
    • , Eisei Sohara
    • , Tatemitsu Rai
    • , Sei Sasaki
    • , Yoshiaki Kondo
    • , Hiroyuki Kagechika
    •  & Shinichi Uchida
  • Article | | open

    The recovery of function upon acute kidney injury is thought to involve tubular cell dedifferentiation and proliferation. Here the authors show that Pax2+ progenitors regenerate tubules via cell division while other tubular cells support function recovery by undergoing hypertrophy through endoreplication.

    • Elena Lazzeri
    • , Maria Lucia Angelotti
    • , Anna Peired
    • , Carolina Conte
    • , Julian A. Marschner
    • , Laura Maggi
    • , Benedetta Mazzinghi
    • , Duccio Lombardi
    • , Maria Elena Melica
    • , Sara Nardi
    • , Elisa Ronconi
    • , Alessandro Sisti
    • , Giulia Antonelli
    • , Francesca Becherucci
    • , Letizia De Chiara
    • , Ricardo Romero Guevara
    • , Alexa Burger
    • , Beat Schaefer
    • , Francesco Annunziato
    • , Hans-Joachim Anders
    • , Laura Lasagni
    •  & Paola Romagnani
  • Article | | open

    Intu is a planar cell polarity protein known to regulate ciliogenesis during embryonic development. Here, Wang et al. identify a role for Intu in adult kidneys, where they find it promotes degradation of STAT1 and thus prevents cilia loss and cell death upon ischemia-reperfusion injury.

    • Shixuan Wang
    • , Aimin Liu
    • , Guangyu Wu
    • , Han-Fei Ding
    • , Shuang Huang
    • , Stanley Nahman
    •  & Zheng Dong
  • Article | | open

    Polycystic kidney disease (PKD) is characterized by the formation of large fluid-filled cysts. Here Flowers and colleagues show that loss of Lkb1, downregulated in PKD, renders kidney cells dependent on glutamine for growth, and suggest that inhibition of glutamine metabolism may prevent cyst development in PKD.

    • Ebony M. Flowers
    • , Jessica Sudderth
    • , Lauren Zacharias
    • , Glenda Mernaugh
    • , Roy Zent
    • , Ralph J. DeBerardinis
    •  & Thomas J. Carroll
  • Article | | open

    In a lupus environment, basophils accumulate in secondary lymphoid organs where they affect pathogenesis by stimulating autoantibody production. Here the authors show this accumulation is driven by PGD2-induced CXCR4 surface expression and trafficking of basophils.

    • Christophe Pellefigues
    • , Barbara Dema
    • , Yasmine Lamri
    • , Fanny Saidoune
    • , Nathalie Chavarot
    • , Charlotte Lohéac
    • , Emeline Pacreau
    • , Michael Dussiot
    • , Caroline Bidault
    • , Florian Marquet
    • , Mathieu Jablonski
    • , Jonathan M. Chemouny
    • , Fanny Jouan
    • , Antoine Dossier
    • , Marie-Paule Chauveheid
    • , Delphine Gobert
    • , Thomas Papo
    • , Hajime Karasuyama
    • , Karim Sacré
    • , Eric Daugas
    •  & Nicolas Charles
  • Article | | open

    The human TNFAIP3 gene, which encodes for A20, is associated with autoimmune diseases. Here, the authors use BAC transgenics combined with CRISPR- and recombineering-mediated genome editing to dissect in vivo and in primary immune cells, the role of enhancers regulating TNFAIP3.

    • Upneet K. Sokhi
    • , Mark P. Liber
    • , Laura Frye
    • , Sungho Park
    • , Kyuho Kang
    • , Tania Pannellini
    • , Baohong Zhao
    • , Rada Norinsky
    • , Lionel B. Ivashkiv
    •  & Shiaoching Gong
  • Article | | open

    Nephropathic cystinosis is a lysosomal storage disease characterized by proximal tubular cell dysfunction. Here Festa and colleagues show that these lysosomal alterations lead to defective autophagic clearance of mitochondria and increased oxidative stress that, in turn, activates the transcription factor ZONAB leading to impaired cell differentiation.

    • Beatrice Paola Festa
    • , Zhiyong Chen
    • , Marine Berquez
    • , Huguette Debaix
    • , Natsuko Tokonami
    • , Jenny Ann Prange
    • , Glenn van de Hoek
    • , Cremonesi Alessio
    • , Andrea Raimondi
    • , Nathalie Nevo
    • , Rachel H. Giles
    • , Olivier Devuyst
    •  & Alessandro Luciani
  • Article | | open

    Mutations in VHL have been linked to clear cell renal cancer, but the molecular mechanisms involved remain unclear. Here the authors generate a mouse model closely mimicking the human disease and show that VHL loss induces DNA replication stress that is rescued by the concomitant loss of PBRM1 permitting transformation.

    • Judit Espana-Agusti
    • , Anne Warren
    • , Su Kit Chew
    • , David J. Adams
    •  & Athena Matakidou
  • Article | | open

    Patients with diabetic nephropathy suffer from impaired albumin reabsorption by proximal tubular epithelial cells. Here authors use diabetic and transgenic mouse models and in vitro models to show the cause for this lies in the down regulation and internalization of the ion channels, ORAI1-3.

    • Bo Zeng
    • , Gui-Lan Chen
    • , Eliana Garcia-Vaz
    • , Sunil Bhandari
    • , Nikoleta Daskoulidou
    • , Lisa M. Berglund
    • , Hongni Jiang
    • , Thomas Hallett
    • , Lu-Ping Zhou
    • , Li Huang
    • , Zi-Hao Xu
    • , Viji Nair
    • , Robert G. Nelson
    • , Wenjun Ju
    • , Matthias Kretzler
    • , Stephen L. Atkin
    • , Maria F. Gomez
    •  & Shang-Zhong Xu
  • Article | | open

    Crescentic rapidly progressive glomerulonephritis is a severe form of glomerula disease characterized by podocyte proliferation and migration. Here Henique et al. demonstrate that inhibition of miRNA-92a prevents kidney failure by promoting the expression of CDK inhibitor p57Kip2 that regulates podocyte cell cycle.

    • Carole Henique
    • , Guillaume Bollée
    • , Xavier Loyer
    • , Florian Grahammer
    • , Neeraj Dhaun
    • , Marine Camus
    • , Julien Vernerey
    • , Léa Guyonnet
    • , François Gaillard
    • , Hélène Lazareth
    • , Charlotte Meyer
    • , Imane Bensaada
    • , Luc Legrès
    • , Takashi Satoh
    • , Shizuo Akira
    • , Patrick Bruneval
    • , Stefanie Dimmeler
    • , Alain Tedgui
    • , Alexandre Karras
    • , Eric Thervet
    • , Dominique Nochy
    • , Tobias B. Huber
    • , Laurent Mesnard
    • , Olivia Lenoir
    •  & Pierre-Louis Tharaux
  • Article | | open

    Clear cell renal cancers (ccRCC) display elevated intracellular lipid storage. Here the authors show that such lipid accumulation is due to the repression of carnitine palmitoyltransferase 1A (CPT1A) enzyme that impairs fatty acid (FA) transport into the mitochondrion resulting in reduced FA beta oxidation.

    • Weinan Du
    • , Luchang Zhang
    • , Adina Brett-Morris
    • , Brittany Aguila
    • , Janos Kerner
    • , Charles L. Hoppel
    • , Michelle Puchowicz
    • , Dolors Serra
    • , Laura Herrero
    • , Brian I. Rini
    • , Steven Campbell
    •  & Scott M. Welford
  • Article | | open

    The transplantation of tissue-specific progenitor cells may be an approach in organ regeneration. Here the authors show that the nephron progenitor population of a developing mouse kidney, when ablated, can be replaced by exogenously supplied rat nephron progenitors, generating interspecies nephrons.

    • S. Yamanaka
    • , S. Tajiri
    • , T. Fujimoto
    • , K. Matsumoto
    • , S. Fukunaga
    • , B. S. Kim
    • , H. J. Okano
    •  & T. Yokoo
  • Article | | open

    Progressive tubule cell damage results in defects in mitochondrial metabolism and exercise seems to be beneficial during chronic kidney disease. Here Peng et al. show that irisin, an exercise-induced myokine, improves kidney energy metabolism by inhibiting TGF-β type 1 receptors and ameliorates fibrosis.

    • Hui Peng
    • , Qianqian Wang
    • , Tanqi Lou
    • , Jun Qin
    • , Sungyun Jung
    • , Vivekananda Shetty
    • , Feng Li
    • , Yanlin Wang
    • , Xin-hua Feng
    • , William E. Mitch
    • , Brett H. Graham
    •  & Zhaoyong Hu
  • Article | | open

    Renal angiomyolipomas (AML) contain a mix of clonal tumour cells. Here, through reverse tumour engineering experiments, mouse genetics and analyses of human AML tumours, the authors provide evidence that these mesenchymal tumours originate from renal proximal tubule epithelial cells.

    • Ana Filipa Gonçalves
    • , Mojca Adlesic
    • , Simone Brandt
    • , Tomas Hejhal
    • , Sabine Harlander
    • , Lukas Sommer
    • , Olga Shakhova
    • , Peter J. Wild
    •  & Ian J. Frew
  • Article | | open

    Genome-wide association studies of kidney function show enrichment of associated genetic variants in regulatory regions. Here, the authors perform epigenome-wide association studies of kidney function and disease, identifying 19 CpG sites significantly associated with these.

    • Audrey Y. Chu
    • , Adrienne Tin
    • , Pascal Schlosser
    • , Yi-An Ko
    • , Chengxiang Qiu
    • , Chen Yao
    • , Roby Joehanes
    • , Morgan E. Grams
    • , Liming Liang
    • , Caroline A. Gluck
    • , Chunyu Liu
    • , Josef Coresh
    • , Shih-Jen Hwang
    • , Daniel Levy
    • , Eric Boerwinkle
    • , James S. Pankow
    • , Qiong Yang
    • , Myriam Fornage
    • , Caroline S. Fox
    • , Katalin Susztak
    •  & Anna Köttgen
  • Article | | open

    Mesenchymal stromal cells drive renal regeneration following injury. Here, the authors show that human mesenchymal stromal cells, when transplanted into mice with acute kidney injury, stimulate renal tubular cell growth and enhance mitochondrial function via SIRT3.

    • Luca Perico
    • , Marina Morigi
    • , Cinzia Rota
    • , Matteo Breno
    • , Caterina Mele
    • , Marina Noris
    • , Martino Introna
    • , Chiara Capelli
    • , Lorena Longaretti
    • , Daniela Rottoli
    • , Sara Conti
    • , Daniela Corna
    • , Giuseppe Remuzzi
    •  & Ariela Benigni
  • Article | | open

    The incidence of renal cell carcinoma is higher in males than in females due to the different androgen receptor signaling but the molecular mechanisms behind this gender bias are unclear. Here the authors show how androgen receptor expression influences the metastatic route through the regulation of miR-185 and VEGF isoforms.

    • Qingbo Huang
    • , Yin Sun
    • , Xin Ma
    • , Yu Gao
    • , Xintao Li
    • , Yuanjie Niu
    • , Xu Zhang
    •  & Chawnshang Chang
  • Article | | open

    The formation mechanism of abundant calcium oxalate biomaterials is unresolved. Here the authors show the early stages of calcium oxalate formation in pure and citrate-bearing solutions by using a titration set-up in conjunction with solution quenching, transmission electron microscopy and analytical ultracentrifugation.

    • Encarnación Ruiz-Agudo
    • , Alejandro Burgos-Cara
    • , Cristina Ruiz-Agudo
    • , Aurelia Ibañez-Velasco
    • , Helmut Cölfen
    •  & Carlos Rodriguez-Navarro
  • Article | | open

    Podocytes are essential components of the renal glomerular filtration barrier and podocyte dysfunction leads to proteinuric kidney disease. Here Liu et al. show that Sirt6 protects podocytes from apoptosis and inflammation by increasing autophagic flux through inhibition of the Notch pathway.

    • Min Liu
    • , Kaili Liang
    • , Junhui Zhen
    • , Meng Zhou
    • , Xiaojie Wang
    • , Ziying Wang
    • , Xinbing Wei
    • , Yan Zhang
    • , Yu Sun
    • , Zhuanli Zhou
    • , Hua Su
    • , Chun Zhang
    • , Ningjun Li
    • , Chengjiang Gao
    • , Jun Peng
    •  & Fan Yi
  • Article | | open

    Folliculin is a known tumour suppressor but the molecular mechanisms behind this function are unclear. Here the authors show that Folliculin regulates EGFR signalling by modulating its Rab7a-dependent trafficking.

    • Laura A. Laviolette
    • , Julien Mermoud
    • , Isabel A. Calvo
    • , Nicholas Olson
    • , Myriam Boukhali
    • , Ortrud K. Steinlein
    • , Elisabeth Roider
    • , Elke C. Sattler
    • , Dachuan Huang
    • , Bin Tean Teh
    • , Mo Motamedi
    • , Wilhelm Haas
    •  & Othon Iliopoulos
  • Article | | open

    Renal cell carcinoma (RCC) is a common and aggressive malignancy. Here, the authors generate two mouse models of the most common RCC subtypes: the human papillary RCC through MYC activation and clear cell RCC through MYC activation combined with Vhl and Cdkn2a deletion.

    • Sean T. Bailey
    • , Aleisha M. Smith
    • , Jordan Kardos
    • , Sara E. Wobker
    • , Harper L. Wilson
    • , Bhavani Krishnan
    • , Ryoichi Saito
    • , Hyo Jin Lee
    • , Jing Zhang
    • , Samuel C. Eaton
    • , Lindsay A. Williams
    • , Ujjawal Manocha
    • , Dorien J. Peters
    • , Xinchao Pan
    • , Thomas J. Carroll
    • , Dean W. Felsher
    • , Vonn Walter
    • , Qing Zhang
    • , Joel S. Parker
    • , Jen Jen Yeh
    • , Richard A. Moffitt
    • , Janet Y. Leung
    •  & William Y. Kim
  • Article | | open

    Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.

    • Rileen Sinha
    • , Andrew G. Winer
    • , Michael Chevinsky
    • , Christopher Jakubowski
    • , Ying-Bei Chen
    • , Yiyu Dong
    • , Satish K. Tickoo
    • , Victor E. Reuter
    • , Paul Russo
    • , Jonathan A. Coleman
    • , Chris Sander
    • , James J. Hsieh
    •  & A. Ari Hakimi
  • Article | | open

    Nrf2 regulates oxidative and electrophilic stress responses by modulating the expression of enzymes involved in detoxification pathways. Here Suzuki et al. show that Nrf2 activation in early tubular development promotes nephrogenic diabetes insipidus by regulating aquaporin 2 expression and trafficking and water permeability.

    • Takafumi Suzuki
    • , Shiori Seki
    • , Keiichiro Hiramoto
    • , Eriko Naganuma
    • , Eri H. Kobayashi
    • , Ayaka Yamaoka
    • , Liam Baird
    • , Nobuyuki Takahashi
    • , Hiroshi Sato
    •  & Masayuki Yamamoto
  • Article | | open

    Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disease that leads to renal failure. Here Hajarnis et al. show that miR-17 modulates cyst progression in ADPKD through metabolic reprogramming of mitochondria and its inhibition slows cyst development and improves renal functions.

    • Sachin Hajarnis
    • , Ronak Lakhia
    • , Matanel Yheskel
    • , Darren Williams
    • , Mehran Sorourian
    • , Xueqing Liu
    • , Karam Aboudehen
    • , Shanrong Zhang
    • , Kara Kersjes
    • , Ryan Galasso
    • , Jian Li
    • , Vivek Kaimal
    • , Steven Lockton
    • , Scott Davis
    • , Andrea Flaten
    • , Joshua A. Johnson
    • , William L. Holland
    • , Christine M. Kusminski
    • , Philipp E. Scherer
    • , Peter C. Harris
    • , Marie Trudel
    • , Darren P. Wallace
    • , Peter Igarashi
    • , Edmund C. Lee
    • , John R. Androsavich
    •  & Vishal Patel
  • Article | | open

    The polyol pathway, which converts glucose into sorbitol and fructose, is active in chronic conditions like hepatic steatosis and chronic kidney disease. Here, Andres-Hernando et al. show that fructose production promotes renal injury and fructokinase inhibition protects against kidney damage during ischaemic acute kidney disease.

    • Ana Andres-Hernando
    • , Nanxing Li
    • , Christina Cicerchi
    • , Shinichiro Inaba
    • , Wei Chen
    • , Carlos Roncal-Jimenez
    • , Myphuong T. Le
    • , Michael F. Wempe
    • , Tamara Milagres
    • , Takuji Ishimoto
    • , Mehdi Fini
    • , Takahiko Nakagawa
    • , Richard J. Johnson
    •  & Miguel A. Lanaspa
  • Article | | open

    Acute kidney injury can progress to chronic kidney disease. Here Dehnadi et al. develop a post-ischaemic chronic kidney disease model in cynomolgus monkeys and show that prophylactic inhibition of CD11b/CD18 leukocyte receptor via a monoclonal antibody inhibits progression of kidney disease and fibrosis.

    • Abbas Dehnadi
    • , A. Benedict Cosimi
    • , Rex Neal Smith
    • , Xiangen Li
    • , José L. Alonso
    • , Terry K. Means
    •  & M. Amin Arnaout
  • Article | | open

    T cells contribute to development of high blood pressure but their role in salt-sensitive hypertension is less clear. Liu et al. show that CD8+ T cells upregulate and activate Na-Cl co-transporter NCC in distal convoluted tubules via direct cell-cell contact and ROS-Src activation, leading to Na+ retention and salt-sensitive hypertension.

    • Yunmeng Liu
    • , Tonya M. Rafferty
    • , Sung W. Rhee
    • , Jessica S. Webber
    • , Li Song
    • , Benjamin Ko
    • , Robert S. Hoover
    • , Beixiang He
    •  & Shengyu Mu
  • Article | | open

    The water channel AQP2 mediates the concentration of urine in the kidney. Here Ando et al. show that Wnt5 promotes collecting duct permeability by regulating AQP2 expression and localization through activation of the calmodulin/calcineurin signalling pathway.

    • Fumiaki Ando
    • , Eisei Sohara
    • , Tetsuji Morimoto
    • , Naofumi Yui
    • , Naohiro Nomura
    • , Eriko Kikuchi
    • , Daiei Takahashi
    • , Takayasu Mori
    • , Alain Vandewalle
    • , Tatemitsu Rai
    • , Sei Sasaki
    • , Yoshiaki Kondo
    •  & Shinichi Uchida
  • Article | | open

    Renal tumour-initiating cells (T-ICs) contribute to tumour initiation and progression. Here, the authors show that lncARSR regulates TICs by blocking LATS1-induced YAP phosphorylation facilitating YAP nuclear translocation, which promotes lncARSR transcription, thus forming a feed-forward circuit to promote TIC expansion.

    • Le Qu
    • , Zhenjie Wu
    • , Yaoming Li
    • , Zhipeng Xu
    • , Bing Liu
    • , Feng Liu
    • , Yi Bao
    • , Dengshuang Wu
    • , Jiayi Liu
    • , Anbang Wang
    • , Xiaoyuan Chu
    • , Yinghao Sun
    • , Cheng Chen
    • , Zhengyu Zhang
    •  & Linhui Wang
  • Article | | open

    Iron overload can be either hereditary or acquired via transfusions, and current treatments include the use of iron chelators that have adverse effects in some patients. Here the authors modify siderocalin to enhance iron excretion in urine, and demonstrate therapeutic efficacy in iron overload mouse models.

    • Jonathan Barasch
    • , Maria Hollmen
    • , Rong Deng
    • , Eldad A. Hod
    • , Peter B. Rupert
    • , Rebecca J. Abergel
    • , Benjamin E. Allred
    • , Katherine Xu
    • , Shaun F. Darrah
    • , Yared Tekabe
    • , Alan Perlstein
    • , Rebecca Wax
    • , Efrat Bruck
    • , Jacob Stauber
    • , Kaitlyn A. Corbin
    • , Charles Buchen
    • , Vesna Slavkovich
    • , Joseph Graziano
    • , Steven L. Spitalnik
    • , Guanhu Bao
    • , Roland K. Strong
    •  & Andong Qiu
  • Article | | open

    Genome-wide association studies have identified multiple loci associated with the risk of developing renal cancer. Here, the authors show that one of these loci generates open chromatin, which enhances the binding of HIF and HIF-mediated transactivation of MYC.

    • Steffen Grampp
    • , James L. Platt
    • , Victoria Lauer
    • , Rafik Salama
    • , Franziska Kranz
    • , Viviana K. Neumann
    • , Sven Wach
    • , Christine Stöhr
    • , Arndt Hartmann
    • , Kai-Uwe Eckardt
    • , Peter J. Ratcliffe
    • , David R. Mole
    •  & Johannes Schödel
  • Article | | open

    A subset of renal cell carcinomas have uncertain histology and are aggressive in nature. Here, the authors examine this group of unclassified renal cancers using genomics techniques and identify further subclasses of the tumours that have differing prognoses.

    • Ying-Bei Chen
    • , Jianing Xu
    • , Anders Jacobsen Skanderup
    • , Yiyu Dong
    • , A. Rose Brannon
    • , Lu Wang
    • , Helen H. Won
    • , Patricia I. Wang
    • , Gouri J. Nanjangud
    • , Achim A. Jungbluth
    • , Wei Li
    • , Virginia Ojeda
    • , A. Ari Hakimi
    • , Martin H. Voss
    • , Nikolaus Schultz
    • , Robert J. Motzer
    • , Paul Russo
    • , Emily H. Cheng
    • , Filippo G. Giancotti
    • , William Lee
    • , Michael F. Berger
    • , Satish K. Tickoo
    • , Victor E. Reuter
    •  & James J. Hsieh
  • Article | | open

    Nephropathy is a common and hard-to-treat consequence of diabetes. Here Kato et al. show that a megacluster of microRNAs regulates early development of diabetic nephropathy in mice, and that inhibition of the cluster's host long non-coding RNA transcript attenuates disease symptoms, suggesting a new therapy for diabetic nephropathy.

    • Mitsuo Kato
    • , Mei Wang
    • , Zhuo Chen
    • , Kirti Bhatt
    • , Hyung Jung Oh
    • , Linda Lanting
    • , Supriya Deshpande
    • , Ye Jia
    • , Jennifer Y.C. Lai
    • , Christopher L. O’Connor
    • , YiFan Wu
    • , Jeffrey B. Hodgin
    • , Robert G. Nelson
    • , Markus Bitzer
    •  & Rama Natarajan
  • Article | | open

    Cancer immunotherapy can be used in combination with other therapies for a better response. Here, the authors conduct a phase Ib clinical study and report the clinical activity and the immune response of the anti-PDL1 agent, atezolizumab, in combination with bevacizumab in ten patients with metastatic renal cell carcinoma.

    • Jeffrey J. Wallin
    • , Johanna C. Bendell
    • , Roel Funke
    • , Mario Sznol
    • , Konstanty Korski
    • , Suzanne Jones
    • , Genevive Hernandez
    • , James Mier
    • , Xian He
    • , F. Stephen Hodi
    • , Mitchell Denker
    • , Vincent Leveque
    • , Marta Cañamero
    • , Galina Babitski
    • , Hartmut Koeppen
    • , James Ziai
    • , Neeraj Sharma
    • , Fabien Gaire
    • , Daniel S. Chen
    • , Daniel Waterkamp
    • , Priti S. Hegde
    •  & David F. McDermott
  • Article | | open

    Branching morphogenesis is essential for the formation of most epithelial organs. Here, the authors show that Neurofibromatosis 2 (NF2), the Hippo pathway kinases LATS1 and LATS2, and the transcriptional co-activators YAP and TAZ control tip identity, RET signalling and branching morphogenesis in the mouse kidney.

    • Antoine Reginensi
    • , Leonie Enderle
    • , Alex Gregorieff
    • , Randy L. Johnson
    • , Jeffrey L. Wrana
    •  & Helen McNeill
  • Article | | open

    A common susceptibility haplotype for renal cell carcinoma is located on chromosome 12p12.1. Here, the authors show that the variant rs7132434 alters binding of the AP-1 transcription factor, which increases the expression of BHLHE41 in renal cells.

    • Pierre Bigot
    • , Leandro M. Colli
    • , Mitchell J. Machiela
    • , Lea Jessop
    • , Timothy A. Myers
    • , Julie Carrouget
    • , Sarah Wagner
    • , David Roberson
    • , Caroline Eymerit
    • , Daniel Henrion
    •  & Stephen J. Chanock
  • Article | | open

    Podocyte injury is central to kidney dysfunction in diabetic nephropathy. Here the authors show that Msk2 is a target of miR-93 and this interaction mediates pathogenic chromatin remodelling in diabetic nephropathy.

    • Shawn S. Badal
    • , Yin Wang
    • , Jianyin Long
    • , David L. Corcoran
    • , Benny H. Chang
    • , Luan D. Truong
    • , Yashpal S. Kanwar
    • , Paul A. Overbeek
    •  & Farhad R. Danesh