Reviews & Analysis

More than three-quarters of cases of chronic kidney disease are caused by glomerular diseases with glomerulosclerosis, including diabetic kidney disease, hypertensive nephropathy and glomerulonephritis. Studies in 2022 provided insights into the molecular mechanisms that maintain dynamic glomerular structures and the responses of specific glomerular cell types during glomerular disease.

Acute kidney injury (AKI) is a multifactorial syndrome with a complex pathophysiology including different inflammatory cells and mediators. Current research focuses on identifying key contributing pathways, determining high-risk groups, characterizing AKI sub-phenotypes and investigating strategies for therapeutic interventions.

Studies in 2022 have advanced knowledge of pregnancy outcomes in kidney donors and transplant recipients as well as the long-term risks associated with hypertensive disorders of pregnancy. These findings should be used to support shared decision-making and appropriate care of women with or at risk of kidney disease.

Over the past year, trial data have emerged on therapeutic interventions in IgA nephropathy and lupus nephritis, including the effects of different doses of glucocorticoids and several novel targeted therapies. These data, in combination with the discovery of autoantibodies targeting nephrin in minimal change disease, can inform the management of immune-mediated glomerular diseases.

Kidney transplantation is the best therapy for kidney failure, but is limited by donor organ availability and the risks associated with immunosuppression. Studies in 2022 provided encouraging data about the outcomes of COVID-19 among transplant recipients, the effects of changes to organ allocation policy in the US and progress in xenotransplantation, raising hope that the organ shortage can be solved.

Chronic kidney disease (CKD) is known to be associated with cognitive impairment, but the mechanisms that underlie this kidney–brain connection are unclear. A recent study provides evidence that CKD is an independent risk factor for cognitive decline due to cerebral small vessel disease.

Inter-organ interactions are critical for maintaining homeostasis in the body but can contribute to multi-organ dysfunction. Clinical evidence indicates that kidney dysfunction contributes to remote organ dysfunction, but little is known of the underlying mechanisms. Several reports published in 2022 identified critical mediators of kidney crosstalk with distant organs.

This Review discusses the mTORC1 and AMPK nutrient sensing pathways, their downstream effects in kidney cells, their roles in the development of kidney disease and the therapeutic potential of approaches that target these pathways in various chronic kidney diseases.

Gut microbiome studies have potential to provide novel therapeutic targets in chronic kidney disease. Here, the authors not only examine the current state of the field and discuss potential gut-related therapies for targeting uraemic metabolites, but also provide guidelines for improving microbiome study design, and data collection and analysis.

Disruptions in oxalate homeostasis can lead to kidney disease and cardiovascular complications. Here, the authors review the pathways that regulate oxalogenesis and the excretion of both exogenous and endogenous oxalate, consider the pathological effects of excess oxalate, and examine the latest therapeutic options for addressing oxalate dysregulation.

This Review describes the global epidemiology, clinical course and key complications of youth-onset type 2 diabetes mellitus. The authors also discuss the mechanisms that might underlie the aggressive clinical phenotype of this disease and current management strategies.

Kidney donation and chronic kidney disease are associated with an increased risk of pre-eclampsia. A recent study in pregnant uninephrectomized mice provides new insights into the mechanisms that underlie these associations and potential therapeutic strategies.

A new study used metabolic tracing of the three main carbon sources (glucose, glutamine and lipids) on cultured slices of mouse kidneys to identify the dynamic metabolic changes that occur after injury in different segments of the kidney tubule at the single-cell level.

This Review focuses on the potential applications of CRISPR to treat diseases that cannot be overcome by inducing frameshifts or premature stops in coding genes. The authors discuss Cas protein engineering and CRISPR systems beyond Cas9 that create a toolbox to engineer the human genome.

The COVID-19 pandemic was met with large-scale efforts to assess novel and repurposed therapeutic interventions that could reduce patient morbidity and mortality. Here, the authors discuss the different types of therapies available to treat COVID-19, including their relevance to patients with kidney failure and kidney transplant recipients.

Trained immunity refers to the development of immunological memory in innate immune cells. Here, the authors examine the basic features of trained immunity, as well as its role and potential therapeutic targeting in immunopathologies that involve the kidney.

Here, the authors review the mechanisms that underlie cisplatin-induced acute kidney injury and chronic kidney disease. They also discuss the challenges of developing renoprotective approaches for patients receiving cisplatin-based chemotherapy and potential targets for renoprotection.

This Review summarizes the current state of knowledge regarding immunological barriers to xenotransplantation and discusses the major approaches that are being used to overcome these barriers, including immunosuppression, genetic engineering of pigs and tolerance induction.

Immune checkpoint inhibitors are increasingly used as anti-cancer treatments; however, their use can be associated with the development of immune-related adverse events, including acute kidney injury. This Review describes the symptoms, biochemical signs and possible underlying mechanisms of immune checkpoint inhibitor-associated acute kidney injury, and proposes an approach to its diagnosis and management.

The use of peritoneal dialysis (PD) can be advantageous compared with haemodialysis treatment, although several barriers limit its broad implementation. This review examines the epidemiology of peritoneal dialysis (PD) outcomes, including clinical, patient-reported and surrogate PD outcomes.