News & Views

  • 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 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 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 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
  • News & Views |

    Many considered the failure of the SYMPLICITY HTN-3 trial to represent the end of therapeutic renal denervation. However, promising preliminary data from the SPYRAL HTN-OFF MED study and more recently the SPYRAL HTN-ON MED and RADIANCE-HTN SOLO studies support the efficacy of this intervention for blood pressure lowering in patients with hypertension.

    • Markus P. Schlaich
    •  & George L. Bakris
  • News & Views |

    Cytoreductive nephrectomy is the current treatment paradigm for metastatic renal cell carcinoma (RCC). However, the introduction of targeted therapies has dramatically changed the treatment landscape and may limit the role of nephrectomy in this disease. The recent CARMENA trial supports initial medical treatment of patients with RCC and synchronous metastases.

    • Viktor Grünwald
    •  & Axel Bex
  • News & Views |

    Intensive lowering of blood pressure can decrease the risk of death and cardiovascular events in individuals with hypertension. However, a reanalysis of data from the SPRINT and ACCORD trials suggests that intensive blood pressure lowering increases the risk of chronic kidney disease.

    • Maria Luisa S. Sequeira-Lopez
    •  & R. Ariel Gomez
  • News & Views |

    Three reports from the TRACERx Renal study delineate the precise origin and evolution of clear cell renal cell carcinoma in minute detail. The insights gained from these studies might provide improved disease prognostics and identify novel therapeutic targets.

    • Christopher J. Ricketts
    •  & W. Marston Linehan
  • News & Views |

    Technologies such as proteomics provide a snapshot of a specific cellular state but are unable to directly record successive signalling events. Two new CRISPR-mediated analogue multi-event recording apparatus (CAMERA) systems enable sequential recording of endogenous and exogenous signalling events by targeted DNA modifications, thereby allowing systematic interrogation of different cellular states.

    • Nicholas J. Steers
    •  & Ali G. Gharavi
  • News & Views |

    A new subclassification of diabetes based on quantitative traits, including age, body mass index, insulin resistance and β-cell function suggests five clusters with distinct phenotypes and prognoses. This approach may offer a novel way to classify diabetes by providing more information on risks and potential therapeutic strategies.

    • Peter Rossing
  • News & Views |

    An unbiased functional gene knockout screen to identify genes implicated in Hedgehog signalling in primary cilia detected most components of the ciliary machinery and ciliopathy-associated genes, but no kidney-related ciliopathy genes. The 472 hits are a tremendous resource for identifying potential ciliopathy genes and for analysing ciliary function and signalling pathways.

    • Edgar A. Otto
  • News & Views |

    Two new clinical trials together involving nearly 30,000 patients support previous observational evidence that the most common solution used for intravenous fluid therapy in the world is associated with kidney damage. Both trials found that 0.9% saline was inferior to solutions with more physiological chloride concentrations and resulted in greater rates of major adverse kidney events.

    • John A. Kellum
  • News & Views |

    A recent observational study reports that implantable cardioverter defibrillators were not associated with improved survival in patients with heart failure, reduced left ventricular ejection fraction and chronic kidney disease. Further studies are needed to identify which of these high-risk patients are most likely to benefit from this potentially life-saving therapy.

    • Finnian R. Mc Causland
    •  & Marc A. Pfeffer
  • News & Views |

    A genome-wide association study (GWAS) of quantitative traits that incorporated data from GWAS of complex diseases provides clues regarding the relationships between genetic loci, intermediate phenotypes and diseases. Together, the data demonstrate pleiotropy, genetic correlation and cell-type specificity of quantitative traits as predictors of multiple complex diseases.

    • David L. Mattson
  • News & Views |

    Advances in precision medicine have greatly improved outcomes for patients with cancer. New findings that demonstrate a substantial contribution of major chronic diseases and disease markers to the risk of cancer incidence and mortality highlight the impact of chronic disease on cancer risk and suggest that chronic diseases should be targeted in cancer prevention strategies.

    • Andrew S. Allegretti
    •  & Ravi I. Thadhani
  • News & Views |

    The cellular origins of angiomyolipoma and other tuberous sclerosis complex-associated neoplasms are unknown. Now, two studies show that these neoplasms derive from cancer stem cells that originate from multipotent renal epithelial cells. The new findings provide a link between stemness and tumorigenesis in the kidney.

    • Francesca Becherucci
    •  & Paola Romagnani
  • News & Views |

    Focal segmental glomerulosclerosis (FSGS) is a common and progressive form of kidney injury for which treatment options are limited. New findings from a study in animal models of FSGS suggest that a small molecule inhibitor of the TRPC5 ion channel could provide therapeutic benefit.

    • Jenny van der Wijst
    •  & René J. M. Bindels
  • News & Views |

    New data from the PRESERVE trial suggest that administration of N-acetylcysteine and/or sodium bicarbonate does not reduce the incidence of acute kidney injury in patients with chronic kidney disease undergoing angiography. Given the limitations of this study, use of these antioxidants should be considered discretionary until further data becomes available.

    • Richard Solomon
  • News & Views |

    New data from the REPRISE trial confirms that tolvaptan slows the progression of autosomal dominant polycystic disease (ADPKD). Although not yet approved by the United States Food and Drug administration, tolvaptan is now likely to become standard care for early and later stages of ADPKD in Europe and in various countries worldwide.

    • Albert C. M. Ong
  • News & Views |

    Standardized prevention approaches can decrease the incidence of acute kidney injury among high-risk patients. Now, the INPRESS study demonstrates that a personalized intraoperative blood pressure management strategy guided by risk stratification can improve perioperative practice and reduce the risk of organ dysfunction among high-risk patients undergoing major surgery.

    • Azra Bihorac
    •  & Charles E. Hobson
  • News & Views |

    Antiviral treatment options for HCV-infected patients with advanced kidney disease are limited because few clinical trials have tested the efficacy of antiviral drugs in this population. Now, a phase III trial of two pan-genotypic drugs demonstrates excellent viral clearance with minimal adverse events in HCV-infected patients with advanced kidney disease.

    • Marco Ladino
    •  & David Roth
  • News & Views |

    Uncontrolled hypertension is an important clinical problem and is associated with considerable morbidity and mortality. A new report from the SPYRAL HTN-OFF MED researchers, which describes the use of renal denervation in patients with uncontrolled hypertension, might reignite enthusiasm for this technique, while a first-in-human description of endovascular baroreflex amplification from the CALM-FIM_EUR investigators highlights the potential of this new approach to inhibit sympathetic activity.

    • Peter J. Blankestijn
    •  & Michiel L. Bots
  • News & Views |

    Hypertension is a risk factor for chronic kidney disease (CKD), but the optimal blood pressure (BP) target in patients with stage 3–5 CKD is unclear. Now, a meta-analysis reports that more-intensive BP control is associated with a reduced risk of all-cause mortality compared with less-intensive BP goals in this high-risk population.

    • Stephen P. Juraschek
    •  & Lawrence J. Appel