Review Articles

  • Review Article |

    Hepatorenal syndrome type 1 (HRS-1) is a specific type of acute kidney injury (AKI) that is largely considered a functional derangement that ultimately affects renal vasculature tone. This Review describes new insights that suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms might contribute to the development of AKI in patients with cirrhosis.

    • Juan Carlos Q. Velez
    • , George Therapondos
    •  & Luis A. Juncos
  • Review Article |

    The field of nephrology has conducted fewer trials than other medical specialties. Here, the authors discuss how innovations in trial design and conduct could help achieve the goal of conducting a greater number of larger renal trials.

    • William G. Herrington
    • , Natalie Staplin
    •  & Richard Haynes
  • Review Article |

    Here, the authors discuss evidence for a role of NAD+ imbalance in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). They suggest that disruption of NAD+ metabolism may contribute to mechanistic links among AKI, CKD and ageing.

    • Kenneth M. Ralto
    • , Eugene P. Rhee
    •  & Samir M. Parikh
  • Review Article |

    Greater understanding of podocyte biology has improved our understanding of the mechanisms that contribute to the development of nephrotic syndrome. Here, Saleem outlines how our understanding of disease mechanisms that contribute to nephrotic syndrome could transform the classification and treatment of this disease.

    • Moin A. Saleem
  • Review Article |

    Oncometabolites — conventional metabolites that, when aberrantly accumulated, have pro-oncogenic capabilities — have been implicated in renal cell carcinoma (RCC). Here, the authors review the role of oncometabolites in RCC, their origins and downstream effects and their potential applications as novel therapeutic targets and biomarkers.

    • Cissy Yong
    • , Grant D. Stewart
    •  & Christian Frezza
  • Review Article |

    Iron is essential for life but must be strictly regulated to avoid harmful effects. The authors discuss new insights into systemic and cellular iron handling with respect to renal physiology and pathology, current treatment practices and novel therapies for kidney disease.

    • Rachel P. L. van Swelm
    • , Jack F. M. Wetzels
    •  & Dorine. W. Swinkels
  • Review Article |

    Fibroblast growth factor 23 (FGF23) is crucial to phosphate and calcium homeostasis. In this Review, the authors discuss how levels of biologically active FGF23 are controlled by balanced FGF23 transcription and protein cleavage, and how serum iron levels, inflammation and erythropoietin affect that balance.

    • Daniel Edmonston
    •  & Myles Wolf
  • Review Article |

    In this Review, the authors examine current efforts to develop a precision medicine approach that informs the diagnosis and treatment of patients with sepsis. Prognostic and predictive enrichment strategies in sepsis might also provide insight into the mechanisms that drive sepsis-associated acute kidney injury, a common complication of sepsis.

    • Natalja L. Stanski
    •  & Hector R. Wong
  • Review Article |

    Increasing evidence suggests that dysregulation of cellular metabolism has a role in the pathophysiology of autosomal dominant polycystic kidney disease. Here the authors discuss the underlying pathways and review efforts to use pharmacological interventions and lifestyle modifications to slow disease progression.

    • Luis Fernando Menezes
    •  & Gregory G. Germino
  • Review Article |

    Therapeutic modulation of hypoxia-inducible factors, which transduce adaptive transcriptional responses to hypoxia, is an emerging theme in kidney disease. This Review summarizes the hypoxia signalling mechanisms underpinning these novel treatments and highlights key remaining questions relevant to their clinical use.

    • Johannes Schödel
    •  & Peter J. Ratcliffe
  • Review Article |

    Immunological ageing has profound effects on the immune system and its ability to protect the host against infection, cancer and autoimmunity. In this Review, the authors discuss how the processes of immunosenescence and inflammageing drive these age-related changes, and their effects on the ageing kidney.

    • Yuki Sato
    •  & Motoko Yanagita
  • Review Article |

    Intravascular haemolysis and the subsequent release of proinflammatory haemoglobin and haem into the circulation are characteristic of several diseases. This Review discusses the major pathophysiological mechanisms and consequences of intravascular haemolysis with a focus on the kidney, and highlights emerging therapeutic strategies to target haemolysis-related kidney injury.

    • Kristof Van Avondt
    • , Erfan Nur
    •  & Sacha Zeerleder
  • Review Article |

    Acute kidney injury (AKI) is diagnosed by the serum concentration of creatinine (SCr), an insensitive marker of kidney function. The authors of this Review discuss the properties of ideal biomarkers of tubular damage and how they can be combined with SCr-based AKI definitions to provide greater insights into the processes underlying acute tubular injury.

    • Beatriz Desanti De Oliveira
    • , Katherine Xu
    • , Tian H. Shen
    • , Miriam Callahan
    • , Krzysztof Kiryluk
    • , Vivette D. D’Agati
    • , Nicholas P. Tatonetti
    • , Jonathan Barasch
    •  & Prasad Devarajan
  • Review Article |

    Staphylococcus infection-associated glomerulonephritis (SAGN) and acute post-streptococcal glomerulonephritis (APSGN) are the two main types of bacterial infection-associated glomerulonephritis. In this Review, the authors discuss the epidemiology of these diseases, common histopathology findings and the complexities of clinical diagnosis, as well as patient management and renal outcomes.

    • Anjali A. Satoskar
    • , Samir V. Parikh
    •  & Tibor Nadasdy
  • Review Article |

    Kidney organoids have the potential to advance the field of nephrology. Here, the author discusses progress in the development of kidney organoids and describes remaining challenges to the use of these cultures for the study of kidney physiology and disease.

    • Ryuichi Nishinakamura
  • Review Article |

    The microbiome is increasingly recognized as an element that contributes to health and disease. Here, the authors take an ecological approach to describe the impact of factors related to chronic kidney disease on the fitness of different physiological systems and the effects of these changes on microbiota composition.

    • Björn Meijers
    • , Pieter Evenepoel
    •  & Hans-Joachim Anders
  • Review Article |

    Sodium has a crucial role in osmoregulation and fluid balance. In this Review, the authors discuss how sodium is also an important functional modulator of innate and adaptive immune cells and how it might be linked to chronic inflammatory conditions.

    • Nicola Wilck
    • , András Balogh
    • , Lajos Markó
    • , Hendrik Bartolomaeus
    •  & Dominik N. Müller
  • Review Article |

    Various cell types release extracellular DNA traps that protect the host against microbial infections. In this Review, the authors discuss how DNA traps not only participate in pathogen clearance but can also promote vascular disease and autoimmunity.

    • Christoph Daniel
    • , Moritz Leppkes
    • , Luis E. Muñoz
    • , Gunnar Schley
    • , Georg Schett
    •  & Martin Herrmann
  • Review Article |

    This Review describes the mechanisms by which dietary, hormonal and metabolic factors regulate the expression and function of sodium-dependent phosphate cotransporters. The authors discuss the consequences of dysregulated phosphate transport and how understanding of the structure–function relationships of the transporters provides insights into their transport mechanisms.

    • Moshe Levi
    • , Enrico Gratton
    • , Ian C. Forster
    • , Nati Hernando
    • , Carsten A. Wagner
    • , Juerg Biber
    • , Victor Sorribas
    •  & Heini Murer
  • Review Article |

    In this Review, the authors discuss the biology of canonical and non-canonical inflammasomes and inflammasome-forming genes in the kidney, including their different functions in the various kidney compartments and their potential as therapeutic targets.

    • Takanori Komada
    •  & Daniel A. Muruve
  • Review Article |

    Here, the authors discuss the multiple functions of the (pro)renin receptor in physiological processes, including blood pressure regulation, energy metabolism and autophagy, as well as its roles in the pathogenesis of diseases including fibrosis, chronic kidney disease, pre-eclampsia and cancer.

    • Atsuhiro Ichihara
    •  & Midori Sasaki Yatabe
  • Review Article |

    Antimicrobial resistance is an emergent global problem and patients with chronic kidney disease have some of the highest rates of colonization and infection with antibiotic-resistant bacteria (ARB). This Review focuses on the epidemiology, prevention and treatment of infections with ARB.

    • Tina Z. Wang
    • , Rosy Priya L. Kodiyanplakkal
    •  & David P. Calfee
  • Review Article |

    The ubiquitin–proteasome system (UPS) maintains protein homeostasis through the selective degradation of proteins. In addition to degrading short-lived and misfolded proteins, the UPS regulates a multitude of cellular processes, including gene transcription and translation, cell survival and metabolism, and inflammation. This Review provides an overview of UPS-mediated proteostasis, focusing on the involvement of the UPS in renal physiology and pathophysiology.

    • Catherine Meyer-Schwesinger
  • Review Article |

    Hypertension is one of the most common comorbid conditions that is associated with obesity. Here, the authors discuss the complex interactions between renal, hormonal and nervous system factors that link excess adiposity with elevated blood pressure.

    • John E. Hall
    • , Jussara M. do Carmo
    • , Alexandre A. da Silva
    • , Zhen Wang
    •  & Michael E. Hall
  • Review Article |

    Autosomal dominant polycystic kidney disease (ADPKD) is caused by pathogenic mutations in the genes that encode polycystin 1 (PC1) and PC2. In this article, the authors discuss findings from structural and electrophysiological studies that give us insight into the function of polycystins and ADPKD pathogenesis.

    • Dominique Douguet
    • , Amanda Patel
    •  & Eric Honoré
  • Review Article |

    Effective adjuvant therapies are needed to reduce the risk of recurrence of kidney cancer. Here, the authors discuss the results of adjuvant therapy trials, the potential of immune checkpoint inhibitors as adjuvant therapies and the need for multidisciplinary management of patients with resected kidney cancer.

    • Camillo Porta
    • , Laura Cosmai
    • , Bradley C. Leibovich
    • , Thomas Powles
    • , Maurizio Gallieni
    •  & Axel Bex
  • Review Article |

    This Review describes the current understanding of the role of epigenetics and epigenomics in diabetic kidney disease (DKD) and how epigenetic mechanisms might contribute to metabolic memory. The authors also discuss how epigenetic factors and non-coding RNAs could be used as biomarkers and drug targets for DKD diagnosis, prognosis and treatment.

    • Mitsuo Kato
    •  & Rama Natarajan
  • Review Article |

    Glycosylation refers to the addition of carbohydrate chains to proteins and lipids. In this Review, the authors discuss the broad role of glycans in immunity, cancer, xenotransplantation and glomerular filtration and the potential of ‘glycomedicine’.

    • Colin Reily
    • , Tyler J. Stewart
    • , Matthew B. Renfrow
    •  & Jan Novak
  • Review Article |

    This Review describes the reciprocal interactions between the immune system and the intestinal microbiota, focusing on components of the immune system that drive chronic diseases that involve the kidney. The authors also discuss limitations of current approaches to microbiota research and emphasize the need to move beyond studies of correlation to causation.

    • Felix Knauf
    • , J. Richard Brewer
    •  & Richard A. Flavell
  • Review Article |

    Pre-eclampsia is associated with substantial maternal and fetal morbidity and mortality worldwide. Here, the authors discuss the epidemiology, pathogenesis and current and future treatment of pre-eclampsia with a focus on the role of angiogenic imbalance.

    • Elizabeth A. Phipps
    • , Ravi Thadhani
    • , Thomas Benzing
    •  & S. Ananth Karumanchi
  • Review Article |

    This Review describes the main signalling pathways that are coordinated by primary cilia to control developmental processes, tissue plasticity and organ function and how defects in the output of ciliary signalling events are coupled to developmental disorders and disease progression.

    • Zeinab Anvarian
    • , Kirk Mykytyn
    • , Saikat Mukhopadhyay
    • , Lotte Bang Pedersen
    •  & Søren Tvorup Christensen
  • Review Article |

    The plasma accumulation of uraemic solutes seen in chronic kidney disease is associated with dysregulated homeostasis. In this Review, Nigam and Bush discuss uraemic syndrome in the context of the remote sensing and signalling hypothesis, which describes small-molecule-mediated communication between tissues and organs.

    • Sanjay K. Nigam
    •  & Kevin T. Bush
  • Review Article |

    Wilms tumour is the most common renal malignancy of childhood. Here, the authors review the genetic landscape of Wilms tumour and discuss how precision medicine guided by genomic information might lead to new therapeutic approaches and improve patient survival.

    • Taryn Dora Treger
    • , Tanzina Chowdhury
    • , Kathy Pritchard-Jones
    •  & Sam Behjati
  • Review Article |

    This Review presents our current understanding of C3 glomerulopathy. Smith et al. discuss the histopathological diagnosis and the crucial pathogenic role of complement dysregulation. Genetic and acquired drivers of C3 glomerulopathy, potential biomarkers and available treatments are highlighted.

    • Richard J. H. Smith
    • , Gerald B. Appel
    • , Anna M. Blom
    • , H. Terence Cook
    • , Vivette D D’Agati
    • , Fadi Fakhouri
    • , Véronique Fremeaux-Bacchi
    • , Mihály Józsi
    • , David Kavanagh
    • , John D. Lambris
    • , Marina Noris
    • , Matthew C. Pickering
    • , Giuseppe Remuzzi
    • , Santiago Rodriguez de Córdoba
    • , Sanjeev Sethi
    • , Johan Van der Vlag
    • , Peter F. Zipfel
    •  & Carla M. Nester
  • Review Article |

    Macrophages are versatile immune cells that protect the host against infection but can also promote chronic inflammation and fibrosis. In this Review, the authors discuss the diverse roles of macrophages in acute and chronic renal pathology as well as potential therapeutic targets.

    • Patrick Ming-Kuen Tang
    • , David J. Nikolic-Paterson
    •  & Hui-Yao Lan
  • Review Article |

    Uraemic cardiomyopathy is the major phenotype of fatal cardiac disease in patients with end-stage renal disease. This Review focuses on the molecular mechanisms of uraemic cardiomyopathy, crosstalk between these mechanisms and implications for therapy

    • Xiaoliang Wang
    •  & Joseph I. Shapiro
  • Review Article |

    A growing body of evidence suggests that epigenetic regulation is involved in the process of acute kidney injury (AKI) and kidney repair. This Review provides a general overview of the main epigenetic mechanisms that have been linked to AKI and discusses the challenges and therapeutic implications of these findings.

    • Chunyuan Guo
    • , Guie Dong
    • , Xinling Liang
    •  & Zheng Dong
  • Review Article |

    The kidney is a highly vascularized organ and contains a remarkable diversity of endothelial cell populations. Here, the authors describe unique features of the healthy renal endothelium and the pathological mechanisms that can lead to endothelial damage in renal disease.

    • Noemie Jourde-Chiche
    • , Fadi Fakhouri
    • , Laetitia Dou
    • , Jeremy Bellien
    • , Stéphane Burtey
    • , Marie Frimat
    • , Pierre-André Jarrot
    • , Gilles Kaplanski
    • , Moglie Le Quintrec
    • , Vincent Pernin
    • , Claire Rigothier
    • , Marion Sallée
    • , Veronique Fremeaux-Bacchi
    • , Dominique Guerrot
    •  & Lubka T. Roumenina
  • Review Article |

    Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis by modulating renal phosphate absorption, vitamin D metabolism and parathyroid hormone secretion. In this Review, Marc Vervloet discusses the role of FGF23 on phosphate regulation as well as its additional effects in the cardiovascular and immune systems.

    • Marc Vervloet
  • Review Article |

    This Review describes the epidemiology and mechanisms underlying the reciprocal relationship between hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The authors also discuss recommended treatment approaches for patients with HCV infection and CKD, and outline remaining issues in the field.

    • Stanislas Pol
    • , Lucia Parlati
    •  & Michel Jadoul
  • Review Article |

    Klotho proteins are crucial elements of the receptor complex for the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. In this Review, Makoto Kuro-o discusses the functions of the FGF–Klotho endocrine systems in health and disease, including their role in ageing-related disorders.

    • Makoto Kuro-o
  • Review Article |

    Autoimmune diseases and kidney transplantation can result in immune-mediated kidney pathology. In this Review, the authors discuss the roles of effector and regulatory B cells and the efficacy of B cell-targeting therapies in these settings.

    • Kristine Oleinika
    • , Claudia Mauri
    •  & Alan D. Salama
  • Review Article |

    The complement system has a key role in inflammatory reactions that occur before, during and after transplantation. Here, the authors discuss this role and highlight current and future strategies to regulate complement activation and potentially improve outcomes in kidney transplantation.

    • Ali-Reza Biglarnia
    • , Markus Huber-Lang
    • , Camilla Mohlin
    • , Kristina N. Ekdahl
    •  & Bo Nilsson
  • Review Article |

    This Review focuses on the epidemiology, pathogenesis and treatment of dyslipidaemia in patients with chronic kidney disease (CKD) and end-stage renal disease. The authors discuss emerging clinical data on the use of novel lipid-lowering agents and reappraise the 2013 KDIGO Guidelines for Lipid Management in CKD.

    • Charles J. Ferro
    • , Patrick B. Mark
    • , Mehmet Kanbay
    • , Pantelis Sarafidis
    • , Gunnar H. Heine
    • , Patrick Rossignol
    • , Ziad A. Massy
    • , Francesca Mallamaci
    • , Jose M. Valdivielso
    • , Jolanta Malyszko
    • , Marianne C. Verhaar
    • , Robert Ekart
    • , Raymond Vanholder
    • , Gerard London
    • , Alberto Ortiz
    •  & Carmine Zoccali
  • Review Article |

    Here, Johnson and Xue describe various physiological and psychosocial challenges that lead to the sensitization of hypertension. These challenges drive neuroplasticity in the brain network controlling sympathetic tone and blood pressure, and provide a new paradigm for understanding essential hypertension.

    • Alan Kim Johnson
    •  & Baojian Xue
  • Review Article |

    Here, Lam and colleagues review advances in understanding the pathogenesis of tuberous sclerosis complex (TSC). Although rapalogues are effective cytostatic treatments for TSC, the unique metabolic vulnerabilities of cells lacking hamartin and/or tuberin might represent opportunities for developing cytocidal treatments.

    • Hilaire C. Lam
    • , Brian J. Siroky
    •  & Elizabeth P. Henske
  • Review Article |

    Acute kidney injury (AKI) is a life-threatening complication in critically-ill neonates. This Review explores the evidence that intrauterine growth restriction, premature birth and low birth weight contribute to neonatal AKI, and discusses perinatal and postnatal risk factors that enhance the risk of AKI among neonates.

    • Norberto Perico
    • , David Askenazi
    • , Monica Cortinovis
    •  & Giuseppe Remuzzi
  • Review Article |

    This Review explores the mechanistic links underlying the associations between HLA and kidney diseases. The authors discuss how these links might provide insights into disease pathogenesis and describe the clinical implications of these insights.

    • Kate J. Robson
    • , Joshua D. Ooi
    • , Stephen R. Holdsworth
    • , Jamie Rossjohn
    •  & A. Richard Kitching
  • Review Article |

    In this Review, Bonny and Firsov describe the circadian rhythmicity in various renal functions and how disruption or alteration of the circadian clock is associated with kidney dysfunction and disease.

    • Dmitri Firsov
    •  & Olivier Bonny