Reviews & Analysis

Circulating non-coding RNAs (ncRNAs) are derived from specific cell types and can be directly transferred to a variety of cells to affect their function. This Review describes the relevance of circulating ncRNAs to the development of kidney disease and discusses the potential use of circulating ncRNAs as diagnostic factors and therapeutic targets.

Portable, wearable and implantable artificial kidney systems require compact and efficient dialysate regeneration systems and novel membranes for improved toxin removal and long-term patency. Here, the authors discuss efforts to overcome these challenges and future perspectives for achieving miniaturized dialysis.

Human ageing trajectories are highly individual and dependent on genetic and non-genetic factors. An analysis of the interconnectivity of distinct age-related chronic diseases shows that organ-specific chronic diseases accelerate the ageing of other organ systems, which has important implications for mortality. Notably, chronic kidney disease was identified a highly important risk factor for the ageing of other organ systems.

This Review examines the contribution of innate and adaptive immune cells to the pathogenesis of lupus nephritis, including new insights into the molecular mechanisms that drive this disease, such as recognition of endogenous chromatin by endosomal and cytosolic nucleic acid sensors.

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal host constituents. This Review provides an overview of the basis of autoimmune disease with a focus on autoantibodies, given their valuable role as markers for diagnosis, classification and of disease activity.

APOL1 risk variants are associated with an increased risk of chronic kidney disease. Findings from a new study demonstrate that a small molecule, inaxaplin, inhibits APOL1 channel function; furthermore, inaxaplin reduced proteinuria in patients with focal segmental glomerulosclerosis and two APOL1 risk variants.

Transgender persons can face a number of barriers in accessing primary and specialist care that is equitable, inclusive and appropriate for their needs. In this Viewpoint, commissioned to recognize Pride, five researchers with expertise across different disciplines, including nephrology, endocrinology, public health, psychology and sociology, provide their perspectives on key considerations that are required to achieve optimal primary and nephrology care for transgender individuals, including barriers to care and how these might be overcome to ensure that the provision of care is inclusive and safe.

Complement proteins and receptors with intracellular activity — the complosome — have emerged as important regulators of physiological processes. In this Review, the authors examine evidence of complosome activity across a variety of cells and tissues, as well as their contributions to human disease and therapeutic potential.

Here, the authors discuss tertiary lymphoid structure (TLS) development, maintenance and function, with a focus on the roles of TLSs in autoimmune disease, cancer, infection and chronic age-related inflammatory diseases. They also discuss the clinical implications of TLSs in various tissues and diseases.

In this Review, the authors describe biological networks, discuss the properties that make these networks ideal for understanding how diseases arise from complex interactions of molecular and cellular systems, and explore how network medicine can be used to improve understanding of kidney and renovascular diseases.

In this Review, the authors discuss the molecular and cellular mechanisms by which pathogenic variants in various genes cause distal renal tubular acidosis with renal and extrarenal manifestations. They also discuss acquired and incomplete forms of distal renal tubular acidosis.

Renal cell carcinoma is sensitive to immune checkpoint blockade despite having a moderate traditional tumour mutational burden profile. Here, the authors discuss how the high prevalence of frameshift insertion or deletions in renal cell carcinoma, as well as the reactivation of endogenous retroviral gene expression, might provide alternative neoantigens that potentiate responses to immunotherapy.

Despite advances in cell and gene therapy for the treatment of disease, no such interventions currently target the kidney. Here, the authors review the potential for cell and gene therapies to be applied to kidney disease, highlighting recent genetic studies, key technical advances and considerations, and areas for further investigation.

Pathways of regulated cell death may contribute to the pathogenesis of various kidney diseases. Here, the authors provide an overview of the relationship between necroptosis, pyroptosis, ferroptosis and apoptosis, the evidence supporting a role for these regulated pathways of necrosis in kidney disease, strategies for therapeutic targeting and research needs.

Ferroptosis is an iron-dependent mechanism of regulated necrosis that is driven by the robust oxidation of polyunsaturated fatty acid-containing phospholipids. This Review describes the fundamental mechanisms of ferroptosis, the potential contribution of ferroptosis to kidney disease and therapeutic strategies for targeting ferroptosis.

Two studies have applied a mechanical stimulus directly to a cilium, independent of a chemical signal, and demonstrated that force-based bending of a single nodal axoneme is sufficient to induce intraciliary Ca²⁺ flux in a PKD2-dependent manner, which propagates to drive asymmetric gene expression.

In this Review, the authors describe the roles of lysosomes in cellular clearance, autophagy, cell signalling, nutrient sensing and metabolic adaptation. They also discuss lysosome abnormalities in metabolic and autoimmune diseases and potential lysosome-targeting therapeutic strategies.

Sepsis-associated acute kidney injury (SA-AKI) is linked with poor outcomes in critically ill patients. This Consensus Statement from the Acute Disease Quality Initiative discusses the definition, epidemiology and pathophysiology of SA-AKI, fluid, resuscitation and extracorporeal therapies, and the role of biomarkers in risk stratification and diagnosis.

The DNA damage response is essential to genomic stability. Here, the authors discuss DNA damage-induced nephrotoxicity and kidney cancer, and the essential role of DNA repair in kidney homeostasis, as well as its potential to contribute to kidney dysfunction, including the links between DNA damage, cell-cycle control and ciliopathies.

An estimated 10–15% of individuals with hypertension are resistant to available antihypertensive therapies. Findings from two new clinical trials — BrigHTN and PRECISION — that assessed the blood pressure-lowering effects of the aldosterone synthase inhibitor baxdrostat and the dual endothelin receptor antagonist aprocitentan, respectively, suggest these approaches hold promise for patients with treatment-resistant hypertension.