Nephrology

  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    • , Catherine Gong
    • , Lisa Zhang
    • , Emmanuel Edusei
    • , Jennifer Huang
    • , Shady Albakry
    • , Michael J. Satlin
    • , Lars F. Westblade
    • , Carl Crawford
    • , Darshana M. Dadhania
    • , Michelle Lubetzky
    • , Ying Taur
    • , Eric Littman
    • , Lilan Ling
    • , Philip Burnham
    • , Iwijn De Vlaminck
    • , Eric Pamer
    • , Manikkam Suthanthiran
    •  & John Richard Lee
  • Article
    | Open Access

    How reproducible human kidney organoids derived from different iPSC lines are, and how faithful they are to human kidney tissue remain unclear. Here, the authors use four human iPSC lines to derive kidney organoids and show how organoid composition is reproducible, comparable to human tissue and of improved quality after transplantation.

    • Ayshwarya Subramanian
    • , Eriene-Heidi Sidhom
    • , Maheswarareddy Emani
    • , Katherine Vernon
    • , Nareh Sahakian
    • , Yiming Zhou
    • , Maria Kost-Alimova
    • , Michal Slyper
    • , Julia Waldman
    • , Danielle Dionne
    • , Lan T. Nguyen
    • , Astrid Weins
    • , Jamie L. Marshall
    • , Orit Rosenblatt-Rosen
    • , Aviv Regev
    •  & Anna Greka
  • Article
    | Open Access

    Kidney stones form in the presence of overabundance of crystal-forming substances such as Ca2+ and oxalate. Here, the authors report genome-wide association analyses for kidney stone disease, report seven previously unknown loci and find that some of these loci also associate with Ca2+ concentration and excretion.

    • Sarah A. Howles
    • , Akira Wiberg
    • , Michelle Goldsworthy
    • , Asha L. Bayliss
    • , Anna K. Gluck
    • , Michael Ng
    • , Emily Grout
    • , Chizu Tanikawa
    • , Yoichiro Kamatani
    • , Chikashi Terao
    • , Atsushi Takahashi
    • , Michiaki Kubo
    • , Koichi Matsuda
    • , Rajesh V. Thakker
    • , Benjamin W. Turney
    •  & Dominic Furniss
  • Article
    | Open Access

    The use of immune checkpoint inhibitors (ICI) in cancer patients with solid organ allografts is hampered due to potential organ rejection. Here, the authors present a case report of a patient with kidney allograft and show that treatment with the mTOR inhibitor sirolimus preserves peripheral tolerance and anti-tumour efficacy of ICI therapy.

    • Khashayar Esfahani
    • , Tho-Alfakar Al-Aubodah
    • , Pamela Thebault
    • , Réjean Lapointe
    • , Marie Hudson
    • , Nathalie A. Johnson
    • , Dana Baran
    • , Najwa Bhulaiga
    • , Tomoko Takano
    • , Jean-François Cailhier
    • , Ciriaco A. Piccirillo
    •  & Wilson H. Miller
  • Article
    | Open Access

    Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.

    • Patricia P. Centeno
    • , Amanda Herberger
    • , Hee-Chang Mun
    • , Chialing Tu
    • , Edward F. Nemeth
    • , Wenhan Chang
    • , Arthur D. Conigrave
    •  & Donald T. Ward
  • Article
    | Open Access

    Arctigenin (ATG) is the major active component of a Chinese herbal remedy known to reduce proteinuria in patients with diabetic kidney disease (DKD). Here, Zhong et al. identify PP2A as a pharmacological target of ATG in podocytes, and find that PP2A is responsible for some of the beneficial effects of ATG in mouse models of DKD.

    • Yifei Zhong
    • , Kyung Lee
    • , Yueyi Deng
    • , Yueming Ma
    • , Yiping Chen
    • , Xueling Li
    • , Chengguo Wei
    • , Shumin Yang
    • , Tianming Wang
    • , Nicholas J. Wong
    • , Alecia N. Muwonge
    • , Evren U. Azeloglu
    • , Weijia Zhang
    • , Bhaskar Das
    • , John Cijiang He
    •  & Ruijie Liu
  • Article
    | Open Access

    Autosomal dominant polycystic kidney disease (ADPKD) is a leading genetic cause of end-stage renal disease with limited treatment options. Here the authors discover and characterize a microRNA inhibitor as a potential treatment for ADPKD.

    • Edmund C. Lee
    • , Tania Valencia
    • , Charles Allerson
    • , Annelie Schairer
    • , Andrea Flaten
    • , Matanel Yheskel
    • , Kara Kersjes
    • , Jian Li
    • , Sole Gatto
    • , Mandeep Takhar
    • , Steven Lockton
    • , Adam Pavlicek
    • , Michael Kim
    • , Tiffany Chu
    • , Randy Soriano
    • , Scott Davis
    • , John R. Androsavich
    • , Salma Sarwary
    • , Tate Owen
    • , Julia Kaplan
    • , Kai Liu
    • , Graham Jang
    • , Steven Neben
    • , Philip Bentley
    • , Timothy Wright
    •  & Vishal Patel
  • Article
    | Open Access

    Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

    • Alexander Teumer
    • , Yong Li
    • , Sahar Ghasemi
    • , Bram P. Prins
    • , Matthias Wuttke
    • , Tobias Hermle
    • , Ayush Giri
    • , Karsten B. Sieber
    • , Chengxiang Qiu
    • , Holger Kirsten
    • , Adrienne Tin
    • , Audrey Y. Chu
    • , Nisha Bansal
    • , Mary F. Feitosa
    • , Lihua Wang
    • , Jin-Fang Chai
    • , Massimiliano Cocca
    • , Christian Fuchsberger
    • , Mathias Gorski
    • , Anselm Hoppmann
    • , Katrin Horn
    • , Man Li
    • , Jonathan Marten
    • , Damia Noce
    • , Teresa Nutile
    • , Sanaz Sedaghat
    • , Gardar Sveinbjornsson
    • , Bamidele O. Tayo
    • , Peter J. van der Most
    • , Yizhe Xu
    • , Zhi Yu
    • , Lea Gerstner
    • , Johan Ärnlöv
    • , Stephan J. L. Bakker
    • , Daniela Baptista
    • , Mary L. Biggs
    • , Eric Boerwinkle
    • , Hermann Brenner
    • , Ralph Burkhardt
    • , Robert J. Carroll
    • , Miao-Li Chee
    • , Miao-Ling Chee
    • , Mengmeng Chen
    • , Ching-Yu Cheng
    • , James P. Cook
    • , Josef Coresh
    • , Tanguy Corre
    • , John Danesh
    • , Martin H. de Borst
    • , Alessandro De Grandi
    • , Renée de Mutsert
    • , Aiko P. J. de Vries
    • , Frauke Degenhardt
    • , Katalin Dittrich
    • , Jasmin Divers
    • , Kai-Uwe Eckardt
    • , Georg Ehret
    • , Karlhans Endlich
    • , Janine F. Felix
    • , Oscar H. Franco
    • , Andre Franke
    • , Barry I. Freedman
    • , Sandra Freitag-Wolf
    • , Ron T. Gansevoort
    • , Vilmantas Giedraitis
    • , Martin Gögele
    • , Franziska Grundner-Culemann
    • , Daniel F. Gudbjartsson
    • , Vilmundur Gudnason
    • , Pavel Hamet
    • , Tamara B. Harris
    • , Andrew A. Hicks
    • , Hilma Holm
    • , Valencia Hui Xian Foo
    • , Shih-Jen Hwang
    • , M. Arfan Ikram
    • , Erik Ingelsson
    • , Vincent W. V. Jaddoe
    • , Johanna Jakobsdottir
    • , Navya Shilpa Josyula
    • , Bettina Jung
    • , Mika Kähönen
    • , Chiea-Chuen Khor
    • , Wieland Kiess
    • , Wolfgang Koenig
    • , Antje Körner
    • , Peter Kovacs
    • , Holly Kramer
    • , Bernhard K. Krämer
    • , Florian Kronenberg
    • , Leslie A. Lange
    • , Carl D. Langefeld
    • , Jeannette Jen-Mai Lee
    • , Terho Lehtimäki
    • , Wolfgang Lieb
    • , Su-Chi Lim
    • , Lars Lind
    • , Cecilia M. Lindgren
    • , Jianjun Liu
    • , Markus Loeffler
    • , Leo-Pekka Lyytikäinen
    • , Anubha Mahajan
    • , Joseph C. Maranville
    • , Deborah Mascalzoni
    • , Barbara McMullen
    • , Christa Meisinger
    • , Thomas Meitinger
    • , Kozeta Miliku
    • , Dennis O. Mook-Kanamori
    • , Martina Müller-Nurasyid
    • , Josyf C. Mychaleckyj
    • , Matthias Nauck
    • , Kjell Nikus
    • , Boting Ning
    • , Raymond Noordam
    • , Jeffrey O’ Connell
    • , Isleifur Olafsson
    • , Nicholette D. Palmer
    • , Annette Peters
    • , Anna I. Podgornaia
    • , Belen Ponte
    • , Tanja Poulain
    • , Peter P. Pramstaller
    • , Ton J. Rabelink
    • , Laura M. Raffield
    • , Dermot F. Reilly
    • , Rainer Rettig
    • , Myriam Rheinberger
    • , Kenneth M. Rice
    • , Fernando Rivadeneira
    • , Heiko Runz
    • , Kathleen A. Ryan
    • , Charumathi Sabanayagam
    • , Kai-Uwe Saum
    • , Ben Schöttker
    • , Christian M. Shaffer
    • , Yuan Shi
    • , Albert V. Smith
    • , Konstantin Strauch
    • , Michael Stumvoll
    • , Benjamin B. Sun
    • , Silke Szymczak
    • , E-Shyong Tai
    • , Nicholas Y. Q. Tan
    • , Kent D. Taylor
    • , Andrej Teren
    • , Yih-Chung Tham
    • , Joachim Thiery
    • , Chris H. L. Thio
    • , Hauke Thomsen
    • , Unnur Thorsteinsdottir
    • , Anke Tönjes
    • , Johanne Tremblay
    • , André G. Uitterlinden
    • , Pim van der Harst
    • , Niek Verweij
    • , Suzanne Vogelezang
    • , Uwe Völker
    • , Melanie Waldenberger
    • , Chaolong Wang
    • , Otis D. Wilson
    • , Charlene Wong
    • , Tien-Yin Wong
    • , Qiong Yang
    • , Masayuki Yasuda
    • , Shreeram Akilesh
    • , Murielle Bochud
    • , Carsten A. Böger
    • , Olivier Devuyst
    • , Todd L. Edwards
    • , Kevin Ho
    • , Andrew P. Morris
    • , Afshin Parsa
    • , Sarah A. Pendergrass
    • , Bruce M. Psaty
    • , Jerome I. Rotter
    • , Kari Stefansson
    • , James G. Wilson
    • , Katalin Susztak
    • , Harold Snieder
    • , Iris M. Heid
    • , Markus Scholz
    • , Adam S. Butterworth
    • , Adriana M. Hung
    • , Cristian Pattaro
    •  & Anna Köttgen
  • Article
    | Open Access

    Persistently low levels of estimated glomerular filtration rate (eGFR) are a biomarker of chronic kidney disease. Here, the authors reinterpret the genetic architecture of kidney function across ancestries, to identify not only genes, but the tissue and anatomical contexts of renal homeostasis.

    • Jacklyn N. Hellwege
    • , Digna R. Velez Edwards
    • , Ayush Giri
    • , Chengxiang Qiu
    • , Jihwan Park
    • , Eric S. Torstenson
    • , Jacob M. Keaton
    • , O. D. Wilson
    • , Cassianne Robinson-Cohen
    • , Cecilia P. Chung
    • , Christianne L. Roumie
    • , Derek Klarin
    • , Scott M. Damrauer
    • , Scott L. DuVall
    • , Edward Siew
    • , Elvis A. Akwo
    • , Matthias Wuttke
    • , Mathias Gorski
    • , Man Li
    • , Yong Li
    • , J. Michael Gaziano
    • , Peter W. F. Wilson
    • , Philip S. Tsao
    • , Christopher J. O’Donnell
    • , Csaba P. Kovesdy
    • , Cristian Pattaro
    • , Anna Köttgen
    • , Katalin Susztak
    • , Todd L. Edwards
    •  & Adriana M. Hung
  • Article
    | Open Access

    The glomerular filtration barrier is a complex structure in charge of renal ultrafiltration. Here the authors present a glomerulus-on-a-chip for disease modelling and high-throughput drug screening where human podocytes and human glomerular endothelial cells are separated by an extracellular matrix resembling the in vivo basement membrane.

    • Astgik Petrosyan
    • , Paolo Cravedi
    • , Valentina Villani
    • , Andrea Angeletti
    • , Joaquin Manrique
    • , Alessandra Renieri
    • , Roger E. De Filippo
    • , Laura Perin
    •  & Stefano Da Sacco
  • Article
    | Open Access

    Recurrent urinary tract infections occur in ~ 25% of women. Here, Beatson and colleagues use whole genome sequencing to track the dynamics of an E. coli ST131 clone in a single patient over a 5-year period. This study provides unique insights into pathogen evolution during recurrent urinary infection.

    • Brian M. Forde
    • , Leah W. Roberts
    • , Minh-Duy Phan
    • , Kate M. Peters
    • , Brittany A. Fleming
    • , Colin W. Russell
    • , Sara M. Lenherr
    • , Jeremy B. Myers
    • , Adam P. Barker
    • , Mark A. Fisher
    • , Teik-Min Chong
    • , Wai-Fong Yin
    • , Kok-Gan Chan
    • , Mark A. Schembri
    • , Matthew A. Mulvey
    •  & Scott A. Beatson
  • Article
    | Open Access

    Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.

    • Raha Pazoki
    • , Evangelos Evangelou
    • , David Mosen-Ansorena
    • , Rui Climaco Pinto
    • , Ibrahim Karaman
    • , Paul Blakeley
    • , Dipender Gill
    • , Verena Zuber
    • , Paul Elliott
    • , Ioanna Tzoulaki
    •  & Abbas Dehghan
  • Article
    | Open Access

    Autoreactivity to myeloperoxidase (MPO) causes autoimmune vasculitis and severe glomerulonephritis. Here, Ooi et al. show that a Staphylococcus aureus plasmid encodes a peptide that is homologous to an immunodominant MPO epitope and induces anti-MPO autoimmunity and glomerulonephritis in mice.

    • Joshua D. Ooi
    • , Jhih-Hang Jiang
    • , Peter J. Eggenhuizen
    • , Ling L. Chua
    • , Mirjan van Timmeren
    • , Khai L. Loh
    • , Kim M. O’Sullivan
    • , Poh Y. Gan
    • , Yong Zhong
    • , Kirill Tsyganov
    • , Lani R. Shochet
    • , Jessica Ryan
    • , Coen A. Stegeman
    • , Lars Fugger
    • , Hugh H. Reid
    • , Jamie Rossjohn
    • , Peter Heeringa
    • , Stephen R. Holdsworth
    • , Anton Y. Peleg
    •  & A. Richard Kitching
  • Article
    | Open Access

    In both focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN), kidney injury is characterised by the invasion of glomerular tufts by parietal epithelial cells (PECs). Here Lazareth et al. identify the tetraspanin CD9 as a key regulator of PEC migration, and find its upregulation in FSGS and CGN contributes to kidney injury in both diseases.

    • Hélène Lazareth
    • , Carole Henique
    • , Olivia Lenoir
    • , Victor G. Puelles
    • , Martin Flamant
    • , Guillaume Bollée
    • , Cécile Fligny
    • , Marine Camus
    • , Lea Guyonnet
    • , Corinne Millien
    • , François Gaillard
    • , Anna Chipont
    • , Blaise Robin
    • , Sylvie Fabrega
    • , Neeraj Dhaun
    • , Eric Camerer
    • , Oliver Kretz
    • , Florian Grahammer
    • , Fabian Braun
    • , Tobias B. Huber
    • , Dominique Nochy
    • , Chantal Mandet
    • , Patrick Bruneval
    • , Laurent Mesnard
    • , Eric Thervet
    • , Alexandre Karras
    • , François Le Naour
    • , Eric Rubinstein
    • , Claude Boucheix
    • , Antigoni Alexandrou
    • , Marcus J. Moeller
    • , Cédric Bouzigues
    •  & Pierre-Louis Tharaux
  • Article
    | Open Access

    Single-cell studies in solid tissues remain challenging and have benefited from the development of single-nuclei RNA sequencing strategies. Here Lake et al. apply single-nucleus RNA sequencing to human kidney tissues to provide a comprehensive molecular and cellular atlas of the human kidney, with potential implications for the understanding of kidney physiology and disease.

    • Blue B. Lake
    • , Song Chen
    • , Masato Hoshi
    • , Nongluk Plongthongkum
    • , Diane Salamon
    • , Amanda Knoten
    • , Anitha Vijayan
    • , Ramakrishna Venkatesh
    • , Eric H. Kim
    • , Derek Gao
    • , Joseph Gaut
    • , Kun Zhang
    •  & Sanjay Jain
  • Article
    | Open Access

    In vivo decorporation of U(VI) from bones is an unsolved challenge because of the formation of stable uranium phosphate complexes. Here, the authors develop a hydroxypyridonone-based ligand with strong uranium complexation and low cytotoxicity. They find this ligand effectively removes uranium from kidney and bones in mice, and is suitable for oral administration.

    • Xiaomei Wang
    • , Xing Dai
    • , Cen Shi
    • , Jianmei Wan
    • , Mark A. Silver
    • , Linjuan Zhang
    • , Lanhua Chen
    • , Xuan Yi
    • , Bizheng Chen
    • , Duo Zhang
    • , Kai Yang
    • , Juan Diwu
    • , Jianqiang Wang
    • , Yujie Xu
    • , Ruhong Zhou
    • , Zhifang Chai
    •  & Shuao Wang
  • Article
    | Open Access

    Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme known to affect membrane lipid composition. Here, Mitrofanova et al. show that increased expression of SMPDL3b in diabetes impairs insulin signaling and ceramide-1-phosphate (C1P) availability in podocytes, and that C1P supplementation protects mice from diabetic kidney disease.

    • A. Mitrofanova
    • , S. K. Mallela
    • , G. M. Ducasa
    • , T. H. Yoo
    • , E. Rosenfeld-Gur
    • , I. D. Zelnik
    • , J. Molina
    • , J. Varona Santos
    • , M. Ge
    • , A. Sloan
    • , J. J. Kim
    • , C. Pedigo
    • , J. Bryn
    • , I. Volosenco
    • , C. Faul
    • , Y. H. Zeidan
    • , C. Garcia Hernandez
    • , A. J. Mendez
    • , I. Leibiger
    • , G. W. Burke
    • , A. H. Futerman
    • , L. Barisoni
    • , Y. Ishimoto
    • , R. Inagi
    • , S. Merscher
    •  & A. Fornoni
  • Article
    | Open Access

    Patients with diabetes commonly develop diabetic kidney disease (DKD). Here Gluck et al. identify a set of probes differentially methylated in renal samples from patients with DKD, and find that inclusion of these methylation probes improves current prediction models of renal function decline.

    • Caroline Gluck
    • , Chengxiang Qiu
    • , Sang Youb Han
    • , Matthew Palmer
    • , Jihwan Park
    • , Yi-An Ko
    • , Yuting Guan
    • , Xin Sheng
    • , Robert L. Hanson
    • , Jing Huang
    • , Yong Chen
    • , Ae Seo Deok Park
    • , Maria Concepcion Izquierdo
    • , Ioannis Mantzaris
    • , Amit Verma
    • , James Pullman
    • , Hongzhe Li
    •  & Katalin Susztak
  • Article
    | Open Access

    Angiotensin II is known to cause renal inflammation and fibrosis. Here Lu et al. show that levels of circulating miR-103a-3p are elevated in hypertensive nephropathy patients and in an animal model of angiotensin II-induced renal dysfunction, and that miR-103a-3p suppresses SNRK expression leading to the activation of the pro-inflammatory NF-κB pathway in glomerular endothelial cells.

    • Qiulun Lu
    • , Zejun Ma
    • , Ye Ding
    • , Tatiana Bedarida
    • , Liming Chen
    • , Zhonglin Xie
    • , Ping Song
    •  & Ming-Hui Zou
  • Article
    | Open Access

    Kinase inhibitors used in chemotherapy are known for their adverse effects on kidney physiology. Here, Calizo et al. show that dasatinib is associated with a higher risk of glomerular toxicity compared to other kinase inhibitors, due to deleterious effects on cytoskeletal biomechanics in podocytes.

    • Rhodora C. Calizo
    • , Smiti Bhattacharya
    • , J. G. Coen van Hasselt
    • , Chengguo Wei
    • , Jenny S. Wong
    • , Robert J. Wiener
    • , Xuhua Ge
    • , Nicholas J. Wong
    • , Jia-Jye Lee
    • , Christina M. Cuttitta
    • , Gomathi Jayaraman
    • , Vivienne H. Au
    • , William Janssen
    • , Tong Liu
    • , Hong Li
    • , Fadi Salem
    • , Edgar A. Jaimes
    • , Barbara Murphy
    • , Kirk N. Campbell
    •  & Evren U. Azeloglu
  • Article
    | Open Access

    Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.

    • Malika Arhatte
    • , Gihan S. Gunaratne
    • , Charbel El Boustany
    • , Ivana Y. Kuo
    • , Céline Moro
    • , Fabrice Duprat
    • , Magali Plaisant
    • , Hélène Duval
    • , Dahui Li
    • , Nicolas Picard
    • , Anais Couvreux
    • , Christophe Duranton
    • , Isabelle Rubera
    • , Sophie Pagnotta
    • , Sandra Lacas-Gervais
    • , Barbara E. Ehrlich
    • , Jonathan S. Marchant
    • , Aaron M. Savage
    • , Fredericus J. M. van Eeden
    • , Robert N. Wilkinson
    • , Sophie Demolombe
    • , Eric Honoré
    •  & Amanda Patel
  • Article
    | Open Access

    Estimated glomerular filtration rate (eGFR) is a measure of kidney function and used to characterize chronic kidney disease. Here, Graham et al. identify 53 novel loci for eGFR in a GWAS meta-analysis, a subset of which are associated with other common diseases, such as diabetes and hypertension, based on PheWAS.

    • Sarah E. Graham
    • , Jonas B. Nielsen
    • , Matthew Zawistowski
    • , Wei Zhou
    • , Lars G. Fritsche
    • , Maiken E. Gabrielsen
    • , Anne Heidi Skogholt
    • , Ida Surakka
    • , Whitney E. Hornsby
    • , Damian Fermin
    • , Daniel B. Larach
    • , Sachin Kheterpal
    • , Chad M. Brummett
    • , Seunggeun Lee
    • , Hyun Min Kang
    • , Goncalo R. Abecasis
    • , Solfrid Romundstad
    • , Stein Hallan
    • , Matthew G. Sampson
    • , Kristian Hveem
    •  & Cristen J. Willer
  • Article
    | Open Access

    Diabetes is a major cause of kidney disease. Here Kikuchi et al. show that phenol sulfate, a gut microbiota-derived metabolite, is increased in diabetic kidney disease and contributes to the pathology by promoting kidney injury, suggesting phenyl sulfate could be used a marker and therapeutic target for the treatment of diabetic kidney disease.

    • Koichi Kikuchi
    • , Daisuke Saigusa
    • , Yoshitomi Kanemitsu
    • , Yotaro Matsumoto
    • , Paxton Thanai
    • , Naoto Suzuki
    • , Koki Mise
    • , Hiroaki Yamaguchi
    • , Tomohiro Nakamura
    • , Kei Asaji
    • , Chikahisa Mukawa
    • , Hiroki Tsukamoto
    • , Toshihiro Sato
    • , Yoshitsugu Oikawa
    • , Tomoyuki Iwasaki
    • , Yuji Oe
    • , Tomoya Tsukimi
    • , Noriko N. Fukuda
    • , Hsin-Jung HO
    • , Fumika Nanto-Hara
    • , Jiro Ogura
    • , Ritsumi Saito
    • , Shizuko Nagao
    • , Yusuke Ohsaki
    • , Satoshi Shimada
    • , Takehiro Suzuki
    • , Takafumi Toyohara
    • , Eikan Mishima
    • , Hisato Shima
    • , Yasutoshi Akiyama
    • , Yukako Akiyama
    • , Mariko Ichijo
    • , Tetsuro Matsuhashi
    • , Akihiro Matsuo
    • , Yoshiaki Ogata
    • , Ching-Chin Yang
    • , Chitose Suzuki
    • , Matthew C. Breeggemann
    • , Jurgen Heymann
    • , Miho Shimizu
    • , Susumu Ogawa
    • , Nobuyuki Takahashi
    • , Takashi Suzuki
    • , Yuji Owada
    • , Shigeo Kure
    • , Nariyasu Mano
    • , Tomoyoshi Soga
    • , Takashi Wada
    • , Jeffrey B. Kopp
    • , Shinji Fukuda
    • , Atsushi Hozawa
    • , Masayuki Yamamoto
    • , Sadayoshi Ito
    • , Jun Wada
    • , Yoshihisa Tomioka
    •  & Takaaki Abe
  • Article
    | Open Access

    Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.

    • Yilong Zou
    • , Michael J. Palte
    • , Amy A. Deik
    • , Haoxin Li
    • , John K. Eaton
    • , Wenyu Wang
    • , Yuen-Yi Tseng
    • , Rebecca Deasy
    • , Maria Kost-Alimova
    • , Vlado Dančík
    • , Elizaveta S. Leshchiner
    • , Vasanthi S. Viswanathan
    • , Sabina Signoretti
    • , Toni K. Choueiri
    • , Jesse S. Boehm
    • , Bridget K. Wagner
    • , John G. Doench
    • , Clary B. Clish
    • , Paul A. Clemons
    •  & Stuart L. Schreiber
  • Article
    | Open Access

    Accurate monitoring of chronic kidney disease (CKD) progression is essential for efficient disease management. Here Chen et al. identify five serum metabolites in patients with stage 1–5 CKD whose levels associate with disease progression, and find that 5-methoxytryptophan and its regulatory enzyme TPH-1 exert anti-fibrotic effects in mouse models of kidney injury.

    • Dan-Qian Chen
    • , Gang Cao
    • , Hua Chen
    • , Christos P. Argyopoulos
    • , Hui Yu
    • , Wei Su
    • , Lin Chen
    • , David C. Samuels
    • , Shougang Zhuang
    • , George P. Bayliss
    • , Shilin Zhao
    • , Xiao-Yong Yu
    • , Nosratola D. Vaziri
    • , Ming Wang
    • , Dan Liu
    • , Jia-Rong Mao
    • , Shi-Xing Ma
    • , Jin Zhao
    • , Yuan Zhang
    • , You-Quan Shang
    • , Huining Kang
    • , Fei Ye
    • , Xiao-Hong Cheng
    • , Xiang-Ri Li
    • , Li Zhang
    • , Mei-Xia Meng
    • , Yan Guo
    •  & Ying-Yong Zhao
  • Article
    | Open Access

    Clear cell renal cell carcinoma (ccRCC) is a urogenital cancer with a well-defined genetic landscape. Here, the authors analyse the clonal architecture of ccRCC patients from three populations, and find prognostic subtypes linked to immune infiltrates and clonal architecture.

    • Yi Huang
    • , Jiayin Wang
    • , Peilin Jia
    • , Xiangchun Li
    • , Guangsheng Pei
    • , Changxi Wang
    • , Xiaodong Fang
    • , Zhongming Zhao
    • , Zhiming Cai
    • , Xin Yi
    • , Song Wu
    •  & Baifeng Zhang
  • Article
    | Open Access

    Vascular calcification is a hallmark of end stage renal disease. Here, Cheng et al. show that poly(ADP-ribose) polymerase (PARP) activity is increased in calcified arteries in patients and uremic rats, and that PARP1 promotes vascular calcification by suppressing miR-204 expression via IL-6/STAT3 signaling, thus relieving repression of the osteogenic regulator Runx2.

    • Cheng Wang
    • , Wenjing Xu
    • , Jie An
    • , Minglu Liang
    • , Yiqing Li
    • , Fengxiao Zhang
    • , Qiangsong Tong
    •  & Kai Huang
  • Article
    | Open Access

    Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis.

    • Saiful E. Syafruddin
    • , Paulo Rodrigues
    • , Erika Vojtasova
    • , Saroor A. Patel
    • , M. Nazhif Zaini
    • , Johanna Burge
    • , Anne Y. Warren
    • , Grant D. Stewart
    • , Tim Eisen
    • , Dóra Bihary
    • , Shamith A. Samarajiwa
    •  & Sakari Vanharanta
  • Article
    | Open Access

    Allograft can induces local chronic inflammation, but how this feeds back to regulating late immunity is still not clear. Here the authors show, by charactering B cell transcriptome landscape dynamic in human allografts and in mouse kidneys transitioning from acute to chronic injury, that late B cell activation is associated with renal dysfunction and inflammation.

    • Pietro E. Cippà
    • , Jing Liu
    • , Bo Sun
    • , Sanjeev Kumar
    • , Maarten Naesens
    •  & Andrew P. McMahon
  • Article
    | Open Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Bulkley
    • , Yong Yu
    • , Jingfeng Tang
    • , Veit Flockerzi
    • , Ying Cao
    • , Erhu Cao
    •  & Xing-Zhen Chen
  • Article
    | Open Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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