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The theme of World Kidney Day 2024 is “kidney health for all — advancing equitable access to care and optimal medication practice”. To mark this event, Nature Reviews Nephrology invited five researchers from different geographical regions worldwide to discuss the impact of new and emerging therapies for diabetic kidney disease on patient care as well as the barriers that must be overcome to ensure equitable access to these therapies.
The widespread availability of single-cell and single-nuclear genomic tools has enabled unbiased and high-dimensional assessment of tissue immunity in the kidney. The application of these technologies to human and mouse kidney samples, combined with spatial transcriptomics, has yielded unexpected insights into how resident and infiltrating immune cells maintain tissue homeostasis and drive disease.
Several successfully completed clinical trials of novel therapies in glomerular disease were reported in 2023. Building on important mechanistic discoveries about disease onset and progression over the past several years, these therapies raise hope that multiple options will be available to reduce the risk of kidney failure in glomerular disease.
Several publications from 2023 have substantiated the importance of altered NAD synthesis in kidney injury and disease progression. Now, NAD deficiency has been linked to the release of mitochondrial RNA and activation of pathways that induce inflammation. Another enzyme that governs mitochondrial function, PCK1, has also now been linked to kidney disease.
The next generation of artificial intelligence (AI)-enabled nephrology will leverage generalist models that link diverse multimodal patient data with the linguistic and emergent capabilities of large language models. In 2023, advances in AI that linked novel unstructured data with physiological and clinical characteristics moved the field closer to realizing this vision.
Despite the availability of effective therapies, the majority of patients with hypertension have poor blood pressure control. Key advances in 2023 have the potential to lead to better treatment adherence and control of blood pressure as well as providing new understanding of postmenopausal hypertension, which may lead to improved therapies.
Basic discovery and clinical trials in diabetic kidney disease (DKD) have continued to be reported in 2023 despite the disruption of research activity by COVID-19 in recent years. Advances in clinical trials and emerging ways to diagnose, monitor and treat DKD dominate the current literature.
Sex differences in immune cell function and immune responses affect the development and outcome of diverse diseases. Here, the authors review current understanding of sex differences in immunity. They describe the key mechanisms that mediate sex differences in immune responses and discuss the functional relevance of such differences for immune-related diseases.
Emerging evidence suggests that cells resident within organs — both immune and parenchymal — can facilitate the instigation and propagation of tissue injury. In this Review, the authors discuss findings that suggest that kidney parenchymal cells provide structural immunity to the kidney through the regulation of immune-relevant processes, with consequences for kidney inflammation and injury.
Improved understanding of kidney disease from a sex- and gender-specific perspective is needed to improve patient care. Here, the authors discuss differences in the epidemiology, management and outcomes of acute kidney injury, chronic kidney disease and kidney failure in men and women.
The demand for kidney transplants is far from met by human donors — a problem that may be solved by the clinical translation of porcine kidney xenotransplantation. A new paper describes the development of genetically ‘humanized’ pigs, the kidneys of which kept nephrectomized cynomolgus macaques alive for up to 2 years.
In this Review, Franck Mauvais-Jarvis discusses how adaptive selection during evolution could have shaped sex differences in energy partitioning, adipose tissue function and distribution, and glucose homeostasis. He also discusses the hormonal and genetic mechanisms that underlie these sex differences and their implications for metabolic disease and sex-based precision medicine.
Clonal haematopoiesis of indeterminate potential (CHIP) is associated with increased risk of disease, including cardiovascular and kidney disease. Here, the authors discuss the consequences of CHIP across various organ systems, including direct and indirect effects on kidney health.
The compartmentalized structure of primary cilia is maintained via interconnected barrier and active transport systems and underlies its unique composition and function. This Review describes the major compartmentalizing pathways that occur at the cilium and how insights into cilia transport and barrier mechanisms have shed light on the mechanisms underlying ciliary diseases.
Although potentially harmful in excess, reactive oxygen species (ROS) also act as signalling molecules and contribute to cell survival. This Review describes the relevance of ROS to physiological processes and disease pathogenesis with a focus on the kidney. The authors also outline the current status of clinical trials that aim to target ROS signalling in humans.
The family of melastatin-like transient receptor potential (TRPM) channels comprises eight multifunctional cation channels. Here, the authors examine the functional role of each TRPM channel, including insights from channelopathies, and discuss the implications for kidney homeostasis and pathology.
New clinical studies suggest that mesenchymal stem cell (MSC) therapy can have positive clinical effects, potentially via immunomodulation, in patients with diabetic nephropathy or nephrotic syndrome. These trials suggest that the therapy is safe, but adverse reactions highlight the need to examine the source and functional attributes of MSCs closely.
Here, the authors discuss the pathophysiology of acute kidney injury (AKI) in patients with burns, approaches to prevention and management of AKI in this population and the application of AKI biomarkers and artificial intelligence approaches to guide treatment and predict short-term and long-term outcomes.
Biomolecular condensates are membraneless compartments that typically contain proteins and RNAs and broadly affect many cell types and organs. In the kidney in particular, rapid and reversible assembly of biomolecular condensates occurs through the process of hyperosmotic phase separation. This Review describes emerging evidence for, and the impact of, biomolecular condensates on kidney physiology and disease.
The complement system is often involved in immune-driven kidney injury. In this Review, the authors discuss complement activation in a variety of kidney diseases, including conditions not traditionally considered to be immune-mediated, and the potential of complement therapeutics for the treatment of kidney disease.