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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.