Review Articles

G protein-coupled receptors (GPCRs) elicit cellular responses to an array of stimuli to regulate the function of virtually all organs. The diverse functions of GPCRs are determined by their expression profiles and their ability to adopt different active and inactive conformations, resulting in functional selectivity or biased signalling. This Review describes the mechanisms and consequences of biased GPCR signalling with a focus on GPCRs of relevance to the kidney.

The ability of the kidney to function normally declines with advancing age. This Review describes ageing processes that are relevant to age-related kidney diseases and the pathological mechanisms of chronic kidney disease in the context of premature ageing, as well as implications for diagnostic and therapeutic interventions.

Here, the authors examine the effect of the rapidly ageing global population on the health and economic burden of chronic kidney disease (CKD). They discuss factors that drive or could mitigate the CKD epidemic and highlight complications and symptoms of CKD that are common among older patients.

Aging of the global population is expected to increase the prevalence of chronic kidney disease. This Review describes approaches to the management of kidney disease in older populations, highlighting the need for a holistic approach aimed at meeting the treatment goals of the patient.

Here, the authors review the impact of IgG glycosylation in kidney diseases, particularly autoimmune diseases and antibody-mediated rejection. They also discuss the signalling pathways that govern antibody glycosylation, the impact of glycosylation on antibody functions and implications for therapy.

In this Review, the authors discuss potential pathophenotypes of coexisting chronic kidney disease and pulmonary hypertension, discuss the principles of clinical management of patients with chronic kidney disease or kidney failure and pulmonary hypertension, and outline key areas for further research.

Perturbations in the regulation of gene expression can contribute to disease- and ageing-associated changes in cell physiology. This review describes how the coordination of gene expression within and between cells can be represented through models of the molecular interactions that govern gene expression levels, and how such models can be used to understand age-associated changes in cell physiology.

In this Review, Owen Lyons discusses the diagnosis, epidemiology and pathophysiology of three sleep disorders that commonly affect patients with chronic kidney disease — restless legs syndrome, insomnia and sleep apnoea — and their impact on patient morbidity and mortality.

In this Review, the authors summarize the mechanistic rationale for current treatments for podocytopathies and for novel podocyte-targeted therapies. They also discuss potential approaches to regenerate podocytes and to develop podocyte-specific drug delivery systems.

Spatially resolved transcriptomic technologies enable the mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. This Review describes current and emerging spatial transcriptomic methods, their applications of relevance to kidney biology and remaining challenges for the field.

Here, the authors discuss the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors for a range of clinical outcomes beyond glucose lowering, including kidney and cardiovascular protection. They also discuss the need for implementation and adherence initiatives to help translate the benefits of these agents into real-world clinical outcomes.

Chronic kidney disease (CKD) is associated with several alterations in protein post-translational modifications. Here, the authors examine the evidence of these alterations, their links with CKD progression and cardiovascular risk in patients with CKD, and their potential clinical applications.

This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity.

Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation.

This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications.

Despite notable progress in basic, clinical and translational nephrology research in the past 50 years, many challenges remain. In this Review, the authors provide an overview of the current status and future directions in nephrology research and patient care.

Several new drug classes have been demonstrated to improve kidney outcomes in people with diabetes mellitus. Here, the authors examine the evidence for the efficacy and safety of combination treatment to reduce the progression of diabetic kidney disease.

Patients with chronic kidney disease often require complex polypharmacy, require dose adjustments or discontinuation with changes in kidney function, and can be susceptible to the adverse effects of medications. This Review discusses the principles of drug stewardship — that is, the effective, safe and sustainable use of medications — for people with chronic kidney disease.

In this Review, the authors examine the biophysical and biomechanical properties that influence podocyte physiology as they integrate and adapt to stimuli from their dynamic environment within the glomerular capillaries. The authors also discuss how dysregulation and loss of biomechanical resilience in podocytes can contribute to kidney disease.

Renal nanomedicines may hold promise for the detection and treatment of a variety of kidney diseases. This Review describes how our understanding of the physiological principles that regulate the glomerular filtration, tubular secretion, luminal tubular uptake and re-elimination of nanoparticles in the kidneys may facilitate the selective targeting of nanomedicines to specific segments of the nephron.