News & Views in 2019

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.