Reviews & Analysis

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  • Cellular senescence has beneficial functions in embryonic development, wound healing and tumour suppression but can also be maladaptive, contributing to cancer development and disease. This Review describes the mechanisms, hallmarks and consequences of senescence, as well as the therapeutic potential of senescence-targeting interventions.

    • Weijun Huang
    • LaTonya J. Hickson
    • Lilach O. Lerman
    Review Article
  • Two recent randomized trials provide evidence to guide the management of sepsis. The CLASSIC trial reports that restrictive fluid therapy has no mortality benefit compared to a standard regimen in patients with septic shock, whereas the LOVIT trial reports that high-dose intravenous vitamin C might be harmful in patients with severe sepsis.

    • Mark Philip Plummer
    • Rinaldo Bellomo
    News & Views
  • Necroptosis is a form of regulated necrosis in which RIPK3 is activated by binding to RIP homotypic interaction motif (RHIM)-containing proteins. Now, researchers describe a non-canonical pathway of RIPK3 activation that is triggered by osmotic stress and NHE1-mediated cytosol alkalinization. This previously undescribed mechanism of osmotic stress-induced necroptosis might have implications for treating cancer and other diseases.

    • Alberto Ortiz
    • Ana B. Sanz
    News & Views
  • Alloimmune T cell responses have a crucial role in graft rejection. Here, the authors examine the factors that regulate T cell activation, differentiation and function in secondary lymphoid organs and in the graft, including the different pathways of allorecognition, innate–adaptive immunity crosstalk and the role of survival cytokines.

    • Charlotte Duneton
    • Pamela D. Winterberg
    • Mandy L. Ford
    Review Article
  • Our understanding of nephrogenesis has been aided by studies that have compared features of human and mouse nephrogenesis, and by technological advances in single-cell omics and high-resolution imaging techniques. This Review describes current understanding of nephron patterning, focusing on the processes by which nephron progenitors are recruited into the developing nephron.

    • Jack Schnell
    • MaryAnne Achieng
    • Nils Olof Lindström
    Review Article
  • The interplay between immunological and metabolic processes is important in a variety of processes. This Review describes how changes in lipid and energy metabolism, driven by receptors of the innate immune system, contribute to the response of tubule epithelial cells to injury and the functional consequences of these intersecting pathways in kidney health and disease.

    • Sanne van der Rijt
    • Jaklien C. Leemans
    • Alessandra Tammaro
    Review Article
  • The fibrogenic niche is a unique tissue microenvironment that promotes fibroblast activation in organ fibrosis. This Review discusses the composition, function and mechanisms of action of the fibrogenic niche in kidney fibrosis, as well as the potential implications of the fibrogenic niche hypothesis for the future diagnosis and treatment of kidney diseases.

    • Li Li
    • Haiyan Fu
    • Youhua Liu
    Review Article
  • The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway not only is involved in host defence against infection but can lead to immune dysregulation. Here, the authors examine the biology and biochemistry of cGAS–STING and discuss its role in disease and potential approaches to therapeutic targeting.

    • Sladjana Skopelja-Gardner
    • Jie An
    • Keith B. Elkon
    Review Article
  • Hypoxia-dependent changes in cellular metabolism have important implications for the effective functioning of multiple immune cell subtypes. This Review describes the inputs that shape the hypoxic response in individual cell types and contexts, and the implications of this response for cellular metabolism and associated alterations in immune cell function.

    • Cormac T. Taylor
    • Carsten C. Scholz
    Review Article
  • Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

    • Allison Tong
    • Nicole Scholes-Robertson
    • Jonathan C. Craig
    Review Article
  • In this Review, the authors discuss the roles of extracellular vesicles in kidney physiology and disease as well as the beneficial effects of stem cell-derived extracellular vesicles in preclinical models of acute kidney injury and chronic kidney disease. They also highlight current and future clinical applications of extracellular vesicles in kidney diseases.

    • Cristina Grange
    • Benedetta Bussolati
    Review Article
  • Chronic kidney disease is associated with an increased risk of cardiovascular disease, such as heart failure. Here, the authors examine myocardial metabolic remodelling in chronic kidney disease, including changes in energy substrate use, mitochondrial dysfunction and the role of cardiotonic steroids, and discuss potential metabolic therapies.

    • Nikayla Patel
    • Muhammad Magdi Yaqoob
    • Dunja Aksentijevic
    Review Article
  • A post hoc analysis of the COAPT trial suggests that transcatheter mitral valve repair for secondary mitral regurgitation is efficacious in patients with heart failure and chronic kidney disease. The intervention also reduced the risk of kidney failure, raising hypotheses regarding the mechanisms that link heart failure and loss of kidney function.

    • Wendy McCallum
    • Mark J. Sarnak
    News & Views
  • Targeting type I interferon immune responses is a potential strategy for the treatment of systemic lupus erythematosus. Although a phase 2 clinical trial of anifrolumab did not meet its primary end point, further studies are needed to assess the effects of interferon blockade on flare rates of lupus nephritis. However, the observed higher risk of herpes zoster associated with anifrolumab use suggests that caution is warranted with this strategy.

    • Stefanie Steiger
    • Hans-Joachim Anders
    News & Views
  • Understanding of the pathogenesis of membranous nephropathy has improved substantially, thanks to the discovery of pathogenic circulating autoantibodies against endogenous antigens. This Review provides an overview of the immunological processes involved in the aetiopathogenesis of membranous nephropathy, including loss of immune tolerance, genetic susceptibility factors and the role of autoantibody binding in the kidney.

    • Elion Hoxha
    • Linda Reinhard
    • Rolf A. K. Stahl
    Review Article
  • Emerging evidence suggests that artificial intelligence (AI)-enabled decision support systems may have an important role in the diagnosis, prognosis and treatment of kidney diseases. This Review provides an overview of AI fundamentals and the state of the art of AI-enabled decision support systems in nephrology.

    • Tyler J. Loftus
    • Benjamin Shickel
    • Azra Bihorac
    Review Article
  • Patients with kidney disease are at particular risk of the adverse outcomes of COVID-19. Throughout the pandemic, epidemiological studies have been performed to inform clinical care; however, these studies have faced a number of methodological challenges. This Review discusses current understanding of the effects of COVID-19 on patients with kidney disease and some of the major obstacles encountered when conducting epidemiological research in a pandemic setting.

    • Viyaasan Mahalingasivam
    • Guobin Su
    • Dorothea Nitsch
    Review Article
  • Drosophila melanogaster can be a useful experimental model in nephrology. Here, the authors examine the fly renal system, focusing on the Malpighian tubules and nephrocytes, and discuss its advantages and limitations as a model system and the mechanistic insights into kidney disease that they have provided.

    • Julian A. T. Dow
    • Matias Simons
    • Michael F. Romero
    Review Article
  • Here, the authors describe the determinants of ‘absolute’ and ‘relative’ glomerular hyperfiltration and discuss single-nephron haemodynamic changes as pathophysiological factors that might result in progressive kidney injury. They also explain how interventions that mitigate glomerular hyperfiltration might translate into long-term renoprotection.

    • Monica Cortinovis
    • Norberto Perico
    • Giuseppe Remuzzi
    Review Article
  • In this Review, the authors focus on kidney involvement in Chagas disease, filariasis, leishmaniasis, malaria and schistosomiasis. They describe the epidemiology, clinical features, mechanisms of kidney injury and renal pathological aspects of these diseases.

    • Elizabeth De Francesco Daher
    • Geraldo Bezerra da Silva Junior
    • Vivekanand Jha
    Review Article