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  • News & Views |

    A new study reports the seroprevalence of SARS-CoV-2 antibodies among a cross-section of patients on haemodialysis and uses these data to estimate seroprevalence in the general US population. Although this study demonstrates the potential of monitoring infectious disease prevalence in dialysis populations, the findings should be interpreted with caution.

    • Viyaasan Mahalingasivam
    •  & Laurie Tomlinson
  • News & Views |

    Recent clinical trials demonstrated that sodium–glucose co-transporter 2 inhibitors can reduce hospitalization for heart failure and improve hard kidney end points in patients with and without type 2 diabetes mellitus. These observations consolidate the view that organ protection is independent of blood glucose control and mitigation of traditional risk factors.

    • Usha Panchapakesan
    •  & Carol Pollock
  • News & Views |

    A new study examined post-mortem kidney tissue from 63 patients with COVID-19. The results suggest that SARS-CoV-2 has kidney tropism, including the ability to replicate in kidney cells, and that kidney transduction by SARS-CoV-2 is associated with shorter survival time and increased incidence of acute kidney injury.

    • Anitha Vijayan
    •  & Benjamin D. Humphreys
  • News & Views |

    Timing of dialysis initiation in critically ill patients is controversial. The STARRT-AKI trial reports that an accelerated initiation strategy did not improve 90-day survival and increased dialysis dependency compared with a standard approach in which patients had greater fluid accumulation and metabolic complications at initiation but 38% avoided dialysis.

    • Josée Bouchard
    •  & Ravindra Mehta
  • News & Views |

    A new study uses the OpenSAFELY health analytics platform to identify risk factors for COVID-19 mortality. This analysis, which includes data for more than 17 million people in the UK, suggests that patients with chronic kidney disease are at higher risk than those with other known risk factors, including chronic heart and lung disease.

    • Ron T. Gansevoort
    •  & Luuk B. Hilbrands
  • News & Views |

    The generation of local immune responses in organs requires a coordinated effort, not just from immune cells, but also from ‘structural’ cells such as epithelial cells, endothelial cells and fibroblasts. New insights gained from profiling these cells across organs in the mouse emphasizes the important contribution of this structural cell network to organ immunity.

    • Zewen Kelvin Tuong
    •  & Menna R. Clatworthy
  • News & Views |

    Long-term immunosuppression in transplant recipients is associated with important adverse effects including increased risk of infection and malignancy. New data from the ONE Study suggests that use of cell-based medicinal products containing regulatory immune cells is a potentially useful therapeutic strategy to enable minimization of immunosuppression in these patients.

    • James M. Mathew
    •  & Joseph R. Leventhal
  • News & Views |

    The mechanism underlying glomerular filtration barrier selectivity has not been resolved. A new study that reports an inverse correlation between slit diaphragm density and proteinuria in a genetic mouse model of focal segmental glomerulosclerosis suggests that podocytes function to compress the glomerular basement membrane (GBM) and that failure of this process results in GBM stretching and increased permeability.

    • Marcus J. Moeller
    •  & Arnaldo Chia-Gil
  • News & Views |

    Clinical trials of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists have shown beneficial effects of these agents on kidney outcomes in patients with type 2 diabetes mellitus. Two new cohort studies now demonstrate that these findings are generalizable to the broad range of patients seen in clinical practice.

    • Annemarie B. van der Aart-van der Beek
    •  & Hiddo J. L. Heerspink
  • News & Views |

    New data suggest that plasma soluble urokinase receptor (suPAR) might be a predictive biomarker and potential therapeutic target for acute kidney injury (AKI). However, many questions remain regarding the potential of suPAR to inform clinical decision making, identify patients for enrolment in clinical trials and add to the understanding of AKI pathogenesis.

    • Sarah Faubel
  • News & Views |

    A recent metabolite genome-wide association study (mGWAS) investigated the relationship between genetic factors and the urine metabolome in kidney disease. The findings demonstrate that mGWAS hold promise for identifying novel genetic factors involved in adsorption, distribution, metabolism and excretion of metabolites and pharmaceuticals, as well as biomarkers for disease progression.

    • Daniel Montemayor
    •  & Kumar Sharma
  • News & Views |

    The PEXIVAS clinical trial demonstrated that, in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV), adjuvant plasma exchange did not reduce the risk of all-cause mortality or end-stage kidney disease and a reduced dose of glucocorticoids was not inferior to standard dosing. These findings might warrant a change in standard AAV therapy.

    • Adam Morris
    •  & Duvuru Geetha
  • News & Views |

    Paradoxically, elevated BMI is a recognized positive prognostic factor in renal cell carcinoma (RCC). A recent investigation of the transcriptomic signatures of RCC tumours and peritumoural tissues suggests potential biological mechanisms underlying this effect. However, the clinical utility of BMI in the context of RCC remains uncertain.

    • Chun Loo Gan
    •  & Daniel Y. C. Heng
  • News & Views |

    Routinely collected data from electronic health records (EHRs) could potentially be used to facilitate clinical trials. Use of computational phenotypes shows promise for detecting trial-eligible paediatric patients; however, moving from EHR identification to recruitment requires consideration of legal, ethical and logistical challenges.

    • Lucy Plumb
    •  & Dorothea Nitsch
  • News & Views |

    The KALM-1 randomized double-blind placebo-controlled phase III trial showed that intravenous difelikefalin, a selective κ-opioid receptor agonist, significantly reduces itch intensity in haemodialysis patients with uraemic pruritus. However, 49% of difelikefalin-treated patients showed no improvement. In light of the increasing number of patients with end-stage renal disease, additional treatments are sorely needed.

    • Elke Weisshaar
    •  & Robert F. Ofenloch
  • News & Views |

    A new study links pathogenic cubilin gene (CUBN) variants to proteinuria without progressive renal impairment, providing reassurance for a subset of patients, calling into question the accepted pathogenesis of glomerulosclerosis and suggesting future therapeutic options.

    • Catherine Quinlan
  • News & Views |

    In recent years, the molecular view of clear cell renal cell carcinoma (ccRCC) has been based primarily on gene transcription data with limited information on protein features. A new study led by the Clinical Proteomic Tumor Analysis Consortium now offers a comprehensive view of the ccRCC proteome.

    • Chad J. Creighton
  • News & Views |

    A new genome-wide association study of patients with type 1 diabetes mellitus reveals novel loci that are associated with the development of diabetic kidney disease. The most significant of these loci encodes the α3 chain of type IV collagen, which is an important component of the glomerular basement membrane.

    • Jeffrey H. Miner
  • News & Views |

    Once confined to the world of science fiction, advances in information technology, particularly in computational and storage resources, have enabled use of artificial intelligence in medicine to become a reality. Two new studies report the use of deep learning — currently the most promising algorithmic artificial intelligence approach — in kidney pathology.

    • Peter Boor
  • News & Views |

    Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with kidney disease. A potential alternative approach is to increase erythropoietin production using small-molecule inhibitors of prolyl hydroxylase domain (PHD) enzymes. Recent phase III trials of the PHD inhibitor roxadustat demonstrate similar efficacy and safety to ESAs.

    • Patrick H. Maxwell
  • News & Views |

    A recent study reports the first high-resolution, cryo-electron microscopy-based structure of zebrafish Na+-K+-Cl cotransporter 1 (NKCC1). This structure provides important insights into the determinants of ion translocation by NKCC1 and other cation-Cl cotransporters such as NKCC2. It could thus facilitate the design of drugs to target these transporters individually.

    • Alexandre P. Garneau
    •  & Paul Isenring
  • News & Views |

    A new study of deep learning based on electronic health records promises to forecast acute kidney injury up to 48 hours before it can be diagnosed clinically. However, employing data science to predict acute kidney injury might be more challenging than it seems.

    • John A. Kellum
    •  & Azra Bihorac
  • News & Views |

    A new study reports important differences between the characteristics of patients with end-stage renal disease on dialysis who are enrolled in clinical trials worldwide and the general US dialysis population. These findings highlight the importance of including older patients and those with comorbidities in clinical trials.

    • Andrew Davenport
  • News & Views |

    Haemorrhagic stroke is more common in adults with chronic kidney disease (CKD) than in the general population. A recent study reports that low concentrations of LDL significantly increase the risk of haemorrhagic stroke. This finding challenges the concept of aggressive lipid lowering in patients with high cardiovascular risk, including those with CKD.

    • Steven Van Laecke
  • News & Views |

    The MENTOR trial reported that rituximab is superior to ciclosporin for remission of nephrotic syndrome in patients with membranous nephropathy. Rituximab is better tolerated than other treatments but, as up to 40% of patients did not respond to rituximab, alternative immunosuppressive therapies may still be required for a substantial minority of patients.

    • Aikaterini Nikolopoulou
    •  & Megan Griffith
  • News & Views |

    Understanding of the cardinal role of the kidneys in maintaining fluid and electrolyte homeostasis is deeply rooted in nephrology. However, the fact that the kidney regulates protein and energy homeostasis similarly to the liver has long been overlooked. Comprehensive whole-body metabolomics studies now shed light on this important aspect of kidney function.

    • Ton J. Rabelink
    •  & Martin Giera
  • News & Views |

    The clinical relevance of minor histocompatibility antigens in transplantation is disputed. High-throughput approaches are now being used to investigate the role of genome-wide genetic incompatibility in transplant outcomes. A recent study reports that donor and recipient mismatch at the LIMS1 locus is associated with an increased risk of acute rejection.

    • Roman Reindl-Schwaighofer
    •  & Rainer Oberbauer
  • News & Views |

    Inhibitors of sodium–glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP4) are widely used in patients with type 2 diabetes to improve glycaemic control and reduce cardiovascular risks. Two recent clinical trials, CREDENCE and DELIGHT, demonstrate that these drugs can also slow down the progression of kidney disease in these patients.

    • Christoph Wanner
    •  & Susanne Brenner
  • News & Views |

    The SONAR trial reports that treatment with the selective endothelin A receptor antagonist atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease. This study was designed to select patients who were likely to benefit from the therapy and minimize the risk of adverse effects.

    • Jennifer S. Pollock
    •  & David M. Pollock
  • News & Views |

    In a collaborative effort, researchers have identified unusual protein deposits of exostosin 1 and exostosin 2 in patients with PLA2R and THSD7A-negative membranous nephropathy, many of whom had systemic lupus erythematosus, lupus nephritis or other forms of autoimmunity. Although serum exostosin antibodies were not detected, the findings suggest that these proteins could define a distinct subtype of membranous nephropathy.

    • Hans-Joachim Anders
  • News & Views |

    Cardiovascular disease (CVD) is a leading cause of death in young adults with incident end-stage renal disease (ESRD). Unlike children with ESRD, young adults with incident ESRD have high prevalence of diabetes, coronary artery disease and heart failure. These cardiovascular risk factors are associated with increased CVD-related hospitalizations and mortality in young adults.

    • Elaine Ku
    •  & Mark M. Mitsnefes
  • News & Views |

    New data from the JAVELIN Renal 101 and KEYNOTE-426 trials provide evidence that immune-based combination therapy has superior efficacy to sunitinib monotherapy in patients with advanced renal cell carcinoma. The new findings raise important questions regarding the optimum choice of combination therapy for these patients.

    • Camillo Porta
    •  & Mimma Rizzo
  • News & Views |

    A new study used genome-wide association data and Mendelian randomization to investigate associations between the gut microbiome and metabolic traits. The researchers demonstrate that host genetic variants influence levels of the short-chain fatty acids butyrate and propionate in the gut, which in turn modulate host glycaemic metabolism.

    • Wei Ling Lau
    •  & Nosratola D. Vaziri
  • News & Views |

    Chronic kidney disease (CKD) is often clinically silent and traditional clinical data alone cannot differentiate disease subtypes. A recent study of the genetic basis of CKD in adults that examined the prevalence of monogenic kidney disease aetiologies supports the use of genetic analysis to improve diagnostics and treatment in CKD.

    • Asaf Vivante
    •  & Karl Skorecki
  • News & Views |

    Haemodialysis options for undocumented immigrants with end-stage renal disease range from standard of care thrice-weekly treatments to emergency-only haemodialysis. This latter approach is associated with poor patient outcomes and high costs. The time has come for the nephrology community to demand an end to the practice of emergency-only haemodialysis.

    • Rudolph A. Rodriguez
  • News & Views |

    The PIVOTAL trial shows that proactive intravenous (i.v.) iron administration reduces cardiovascular events and deaths, transfusions and erythropoiesis-stimulating agent doses and does not increase infections in patients on haemodialysis. These findings upend the warnings of guidelines and experts about the dangers of i.v. iron and prove that maintaining low iron stores is harmful.

    • Daniel W. Coyne
  • News & Views |

    A new study reports that human blood vessel organoids can be generated through the directed differentiation of human pluripotent stem cells. Use of these blood vessel organoids to model diabetic vasculopathy led to the identification of a new potential therapeutic target, suggesting that this system could have translational value for studies of diabetes complications.

    • Ryuji Morizane
  • News & Views |

    A reduction in proteinuria and albuminuria has long been proposed as a surrogate biomarker for clinically validated end points for interventional trials in patients with kidney disease. Taken together, the findings of two recent landmark meta-analyses present a formidable argument favouring such surrogacy but some uncertainty remains.

    • Richard J. Glassock
  • News & Views |

    The analyses in the 2017 Global Burden of Disease Study demonstrate the growing burden of chronic kidney disease (CKD), mainly driven by population ageing; absolute levels for every CKD metric considered rose significantly, whereas age-standardized rates were fairly stable. The prevalence of key metabolic CKD risk factors, particularly obesity, also show a worrying increase.

    • Simon D. S. Fraser
    •  & Paul J. Roderick
  • News & Views |

    New findings demonstrate that endothelial nitric oxide synthase regulates major metabolic pathways in the kidney proximal tubule, which confers protection against oxidative stress during acute kidney injury (AKI). These findings give new insights into AKI pathophysiology and nitric oxide biology, and identify new targets for the treatment of AKI.

    • Pierre-Yves Martin
    •  & Sophie de Seigneux
  • News & Views |

    Scientists have long wondered how maternal diabetes, malnutrition and placental dysfunction impair fetal nephrogenesis. A new study discovered a link between prenatal metabolic stress and nephron deficit via dysregulation of DNA methylation — an epigenetic mechanism that is essential for the renewal and differentiation of nephron progenitors.

    • Samir S. El-Dahr
  • News & Views |

    Peritoneal dialysis has many advantages over haemodialysis in the treatment of acute kidney injury (AKI) in low-resource settings. One limitation, however, is the availability of commercial dialysis fluid. Following the International Society of Peritoneal Dialysis AKI guidelines, a frontline hospital in Cameroon now shows that locally prepared fluids are safe and effective.

    • Simon J. Davies
  • News & Views |

    New findings implicate sodium transport in α-cell secretory dysfunction, leading to impaired counter-regulatory responses in diabetes. However, these findings also raise important questions about the tissue-specific roles of sodium transport and suggest that inhibitors of sodium transport may have potentially divergent roles in the pancreas, kidney and heart.

    • Julie A. Lovshin
    •  & David Z. Cherney
  • News & Views |

    A new study discovered thousands of expression quantitative trait loci (eQTLs) in the renal glomerular and tubulointerstitial compartments and integrated these data with other omics data sets to identify genes with roles in the pathogenesis of chronic kidney disease. This report reinforces the necessity of using compartment-derived eQTLs to advance kidney genomic discovery.

    • Matthew G. Sampson
  • News & Views |

    The IDEAL-ICU study reports no mortality benefit of early versus delayed initiation of renal replacement therapy (RRT) in patients with early septic shock and acute kidney injury. In the delayed initiation group, 17% of patients required emergency RRT but more than one-third spontaneously recovered renal function and did not require RRT.

    • Lui G. Forni
    •  & Michael Joannidis
  • News & Views |

    A genetic study using a Mendelian randomization approach provides evidence that albuminuria — as well as being the result of hypertension — might also cause hypertension and cardiometabolic disease. We suggest that a mechanism behind these findings could involve sodium retention by urinary protein-induced activation of the epithelial sodium channel in the distal tubule.

    • Ron T. Gansevoort
    •  & Harold Snieder
  • News & Views |

    The polycystin complex structure has been solved at near-atomic resolution. Its surprising architecture provides new insights into the transient receptor potential (TRP) family of cation channels and the pathogenesis of autosomal dominant polycystic kidney disease. This discovery should have a transformative impact on the development of treatment strategies to cure the disease.

    • Paul A. Welling
  • News & Views |

    A new study reports that genome-wide polygenic risk scores can identify individuals at risk of common complex diseases, such as coronary artery disease or type 2 diabetes, with comparable performance to that of monogenic mutation screens. These findings support the potential clinical utility of genome-wide association study (GWAS)-based risk stratification; however, several issues need to be addressed before this approach can be applied to kidney disease.

    • Lili Liu
    •  & Krzysztof Kiryluk
  • News & Views |

    The AWARD-7 trial shows that the glucagon-like peptide 1 (GLP1) receptor agonist dulaglutide, which is not cleared by the kidney, seems to be renoprotective, ameliorates albuminuria and slows estimated glomerular filtration rate decline in patients with type 2 diabetes mellitus and chronic kidney disease, without increasing the risk of hypoglycaemia.

    • Charlotte M. Sorensen
    •  & Jens J. Holst
  • News & Views |

    A recent observational study reports that after cardiac surgery, clinical outcomes differ significantly between patients with the same stage of acute kidney injury (AKI) depending on the diagnosis criteria used: urine output, serum creatinine or both. This finding emphasizes the limitations of current criteria for AKI risk stratification and diagnosis.

    • Faeq Husain-Syed
    •  & Claudio Ronco