Reviews & Analysis

Targeting type I interferon immune responses is a potential strategy for the treatment of systemic lupus erythematosus. Although a phase 2 clinical trial of anifrolumab did not meet its primary end point, further studies are needed to assess the effects of interferon blockade on flare rates of lupus nephritis. However, the observed higher risk of herpes zoster associated with anifrolumab use suggests that caution is warranted with this strategy.

Understanding of the pathogenesis of membranous nephropathy has improved substantially, thanks to the discovery of pathogenic circulating autoantibodies against endogenous antigens. This Review provides an overview of the immunological processes involved in the aetiopathogenesis of membranous nephropathy, including loss of immune tolerance, genetic susceptibility factors and the role of autoantibody binding in the kidney.

Emerging evidence suggests that artificial intelligence (AI)-enabled decision support systems may have an important role in the diagnosis, prognosis and treatment of kidney diseases. This Review provides an overview of AI fundamentals and the state of the art of AI-enabled decision support systems in nephrology.

Patients with kidney disease are at particular risk of the adverse outcomes of COVID-19. Throughout the pandemic, epidemiological studies have been performed to inform clinical care; however, these studies have faced a number of methodological challenges. This Review discusses current understanding of the effects of COVID-19 on patients with kidney disease and some of the major obstacles encountered when conducting epidemiological research in a pandemic setting.

Drosophila melanogaster can be a useful experimental model in nephrology. Here, the authors examine the fly renal system, focusing on the Malpighian tubules and nephrocytes, and discuss its advantages and limitations as a model system and the mechanistic insights into kidney disease that they have provided.

Here, the authors describe the determinants of ‘absolute’ and ‘relative’ glomerular hyperfiltration and discuss single-nephron haemodynamic changes as pathophysiological factors that might result in progressive kidney injury. They also explain how interventions that mitigate glomerular hyperfiltration might translate into long-term renoprotection.

In this Review, the authors focus on kidney involvement in Chagas disease, filariasis, leishmaniasis, malaria and schistosomiasis. They describe the epidemiology, clinical features, mechanisms of kidney injury and renal pathological aspects of these diseases.

Advances in the field of single-cell genomics and spatial technologies have enabled dissection of the cellular heterogeneity of complex tissues, including the kidney. This Review summarizes the state of the art of single-cell analyses in kidney research, including advances in our understanding of kidney embryogenesis and pathomechanisms of several relevant kidney disease entities.

This Review summarizes current understanding of the role of APOL1 variants in kidney disease. The authors discuss the genetics, protein structure and biological functions of APOL1 variants and provide an overview of promising therapeutic strategies.

This Review examines the epidemiology of haemodialysis outcomes — clinical, patient-reported and surrogate outcomes — across world regions and populations, including vulnerable individuals. The authors also discuss the current status of monitoring and reporting of haemodialysis outcomes and potential strategies for improvement.

Although direct kidney infection by SARS-CoV-2 remains controversial, a study based largely on autopsies shows increased tubulointerstitial fibrosis in patients with COVID-19 and suggests direct kidney infection. Moreover, in human kidney organoids, SARS-CoV-2 infection upregulates several pro-fibrotic and pro-inflammatory pathways.

Sickle cell syndromes are associated with kidney abnormalities and sickle cell nephropathy. Here, the authors discuss the pathological changes that occur in the kidney and their underlying mechanisms, as well as the detection, treatment and management of kidney disease in patients with sickle cell syndromes.

This Review summarizes the state of the art of acute kidney injury model development, focusing on the translatability of discoveries using human kidney organoid, zebrafish, rodent and large animal models. The authors recommend a multidisciplinary approach to optimize the development of effective therapies for acute kidney injury.

Cockayne syndrome is a genetic disease characterized by impairment of DNA repair mechanisms, premature ageing, cachexia and kidney dysfunction. New research in a mouse model of Cockayne syndrome demonstrates that injury induces a subset of kidney proximal tubule cells to express the anorexigenic peptide GDF15. These findings link kidney injury to cachexia and highlight the role of the kidney in mediating inter-organ homeostasis.

Clinical trials have demonstrated sodium–glucose co-transporter 2 (SGLT2) inhibitors to be safe and effective drugs that improve kidney outcomes in patients with and without diabetes. SGLT2 inhibitors also improve heart failure outcomes for patients with preserved or reduced ejection fraction. This Review summarizes findings from clinical trials of SGLT2 inhibitors, focusing on the effects of these agents in patients with chronic kidney disease and heart failure, and describes how potential mechanisms of action may translate into clinical benefit.

Dapagliflozin reduces the risk of new-onset diabetes mellitus, according to results from a pre-specified pooled analysis of the DAPA-CKD and DAPA-HF trials. The study adds to the growing list of sodium–glucose co-transporter 2 inhibitor benefits and raises the possibility of an expanded target patient population.

A recent clinical trial reports promising efficacy and safety data for belzutifan in patients with von Hippel–Lindau (VHL) disease–associated renal cell carcinoma. On the basis of these results, belzutifan became the first therapeutic agent to be approved for the systemic treatment of cancer associated with VHL disease.

Tissue-resident memory T cells are crucial to immune responses in epithelial and mucosal tissues. This Review examines the unique characteristics and differentiation pathways of these cells, as well as their unique adaptations in the urogenital tract, and their role in infection, cancer, inflammatory diseases and transplantation.

Here, the authors review current approaches to replication of the glomerulus in vitro with a focus on organ-on-a-chip, scaffolding and organoid technologies. They also discuss future directions of research, including the use of newer 3D biofabrication technologies.

Here, the authors discuss the effects of salt intake on health outcomes, the factors that determine individual susceptibility to dietary salt and approaches to reducing salt intake and improving health at the population and individual levels.