Review Articles in 2022

The interplay between immunological and metabolic processes is important in a variety of processes. This Review describes how changes in lipid and energy metabolism, driven by receptors of the innate immune system, contribute to the response of tubule epithelial cells to injury and the functional consequences of these intersecting pathways in kidney health and disease.

The fibrogenic niche is a unique tissue microenvironment that promotes fibroblast activation in organ fibrosis. This Review discusses the composition, function and mechanisms of action of the fibrogenic niche in kidney fibrosis, as well as the potential implications of the fibrogenic niche hypothesis for the future diagnosis and treatment of kidney diseases.

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway not only is involved in host defence against infection but can lead to immune dysregulation. Here, the authors examine the biology and biochemistry of cGAS–STING and discuss its role in disease and potential approaches to therapeutic targeting.

Hypoxia-dependent changes in cellular metabolism have important implications for the effective functioning of multiple immune cell subtypes. This Review describes the inputs that shape the hypoxic response in individual cell types and contexts, and the implications of this response for cellular metabolism and associated alterations in immune cell function.

Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

In this Review, the authors discuss the roles of extracellular vesicles in kidney physiology and disease as well as the beneficial effects of stem cell-derived extracellular vesicles in preclinical models of acute kidney injury and chronic kidney disease. They also highlight current and future clinical applications of extracellular vesicles in kidney diseases.

Chronic kidney disease is associated with an increased risk of cardiovascular disease, such as heart failure. Here, the authors examine myocardial metabolic remodelling in chronic kidney disease, including changes in energy substrate use, mitochondrial dysfunction and the role of cardiotonic steroids, and discuss potential metabolic therapies.

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.

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.

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.

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.