Articles in 2019

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.

In this Review, the authors examine current efforts to develop a precision medicine approach that informs the diagnosis and treatment of patients with sepsis. Prognostic and predictive enrichment strategies in sepsis might also provide insight into the mechanisms that drive sepsis-associated acute kidney injury, a common complication of sepsis.

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.

Therapeutic modulation of hypoxia-inducible factors, which transduce adaptive transcriptional responses to hypoxia, is an emerging theme in kidney disease. This Review summarizes the hypoxia signalling mechanisms underpinning these novel treatments and highlights key remaining questions relevant to their clinical use.

Increasing evidence suggests that dysregulation of cellular metabolism has a role in the pathophysiology of autosomal dominant polycystic kidney disease. Here the authors discuss the underlying pathways and review efforts to use pharmacological interventions and lifestyle modifications to slow disease progression.

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.

Immunological ageing has profound effects on the immune system and its ability to protect the host against infection, cancer and autoimmunity. In this Review, the authors discuss how the processes of immunosenescence and inflammageing drive these age-related changes, and their effects on the ageing kidney.

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.

Intravascular haemolysis and the subsequent release of proinflammatory haemoglobin and haem into the circulation are characteristic of several diseases. This Review discusses the major pathophysiological mechanisms and consequences of intravascular haemolysis with a focus on the kidney, and highlights emerging therapeutic strategies to target haemolysis-related kidney injury.

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.

Acute kidney injury (AKI) is diagnosed by the serum concentration of creatinine (SCr), an insensitive marker of kidney function. The authors of this Review discuss the properties of ideal biomarkers of tubular damage and how they can be combined with SCr-based AKI definitions to provide greater insights into the processes underlying acute tubular injury.

The increasing volumes of biological and clinical data have the potential to greatly enhance our understanding of the processes underlying kidney function and disease. However, maximizing outputs from these data requires a collaborative and open approach to data sharing that can only be achieved through united efforts by researchers, funders and publishers.

Staphylococcus infection-associated glomerulonephritis (SAGN) and acute post-streptococcal glomerulonephritis (APSGN) are the two main types of bacterial infection-associated glomerulonephritis. In this Review, the authors discuss the epidemiology of these diseases, common histopathology findings and the complexities of clinical diagnosis, as well as patient management and renal outcomes.

A critical need exists for innovations in education that increase the recruitment of high school students from diverse backgrounds into the biomedical research workforce. Aspirnaut is one model that addresses this challenge.