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Targeting of CD38 has been posited as a potential therapeutic avenue for the treatment of immune-mediated conditions. A phase 2 study now reports promising safety, tolerability and intermediate endpoint of efficacy outcomes with the anti-CD38 monoclonal antibody felzartamab in kidney transplant recipients with antibody-mediated rejection.

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.

Deep Learning (DL) holds great promise to improve patient outcomes by improving the precision and speed of disease diagnosis and treatment recommendations. Given the efficacy of DL in image analysis, pathology will likely be one of the first medical fields transformed by DL. However, several challenges must be overcome before we can expect to see the use of DL transform the digital future of pathology.

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.

Technological advances continue to enhance the clinical value of kidney biopsies. Here, the authors consider the potential of using spatial-omics in transplantation, including the use of mass spectrometry imaging, as graft monitoring and diagnostic tools, to improve patient management and outcomes.

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.

Graft rejection is traditionally attributed to adaptive immune cells that recognize donor-specific alloantigens, with innate immunity having a secondary role. The finding that recipient natural killer cells are activated by the inability of graft endothelial cells to provide HLA-I-mediated inhibitory signals challenges this dogma and introduces the concept of innate rejection.

Kidneys from older donors might improve the quality of life and survival of patients with kidney failure, yet these organs are often underutilized. Re-framing discussions of organ acceptance from older donors and its benefits over dialysis, especially for older patients and those who cannot tolerate prolonged waiting for transplantation, is urgently needed.

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.

Centenarians — who are a putative model of healthy longevity — often have a low risk of cardiovascular disease, despite an age-associated decline in kidney function. An understanding of the molecular and cellular underpinnings of health kidney ageing in centenarians may provide clues for the prevention or alleviation of the burden of kidney disease in older populations.

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.

American Indian and Alaska Native peoples have low life expectancy and a disproportionate disease burden (including of chronic kidney disease), owing to inadequate education, poverty, discrimination and underfunding in the delivery of health services, and healthcare institutions’ lack of appreciation for cultural differences. These broad quality-of-life issues are rooted in economic adversity and poor social conditions.

The increasing prevalence of chronic kidney disease (CKD) is placing a growing burden on healthcare systems, which results in considerable economic and environmental challenges. Sustainable CKD care and optimization of patient outcomes requires a new approach to the organization of healthcare systems, in which home monitoring will have a pivotal role.