Reviews & Analysis

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.

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.

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.

Kidney organoids have the potential to advance the field of nephrology. Here, the author discusses progress in the development of kidney organoids and describes remaining challenges to the use of these cultures for the study of kidney physiology and disease.

This Perspectives article considers why clinical trials of urate-lowering therapy (ULT) have shown inconsistent renoprotective effects in patients with chronic kidney disease, and suggests that sufficient evidence exists to support the use of routine screening for hyperuricaemia and initiation of ULT in selected patients.

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.

The microbiome is increasingly recognized as an element that contributes to health and disease. Here, the authors take an ecological approach to describe the impact of factors related to chronic kidney disease on the fitness of different physiological systems and the effects of these changes on microbiota composition.

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.

Sodium has a crucial role in osmoregulation and fluid balance. In this Review, the authors discuss how sodium is also an important functional modulator of innate and adaptive immune cells and how it might be linked to chronic inflammatory conditions.