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Kidney health data have long highlighted the disproportionate burden of kidney disease among Indigenous populations across the globe. It is time for meaningful interventions that can create real change.
Effective kidney-targeted therapeutics require careful consideration of both the cargo and carrier. In the past year, considerable progress has been made in the development of viral and non-viral delivery vehicles, by leveraging endogenous biological mechanisms, screening across multiple species and administration routes, and artificial intelligence to drive kidney selectivity.
In 2025, several landmark studies illuminated the sequence of immune events that influence tolerance and rejection in kidney transplantation, from the molecular triggers of allorecognition to the chemotactic control of cytotoxicity and the protective mechanisms underlying the benefits of immune therapies. As xenotransplantation advances, these insights will also be important for achieving sustained xenograft tolerance.
Although 2025 began with disruption and geopolitical retreat, momentum in kidney health advocacy endured. Global, regional and national efforts demonstrated that progress is possible when commitment persists and setbacks are recognized, offering opportunities to lessen the burden of kidney disease and improve access to equitable and sustainable kidney care.
New studies in autoimmune kidney disease demonstrate the complex interplay between immune and non-immune cells that underlies kidney inflammation and fibrosis. Differences between these autoimmune responses and those observed in kidney allograft rejection, as well as insights from clinical responses to immunotherapy, provide further clues on key pathways driving kidney inflammation.
Cardiovascular–kidney–metabolic (CKM) syndrome reflects the intricate connections between metabolic disorders, chronic kidney disease and cardiovascular disease. In 2025, key studies advanced understanding of risk prediction in CKM syndrome, including the role of social determinants of health, as well as combination treatment strategies and potential therapeutic targets to improve CKM health.
Kidneys are highly susceptible to acute injury. Several studies in 2025 revealed insights into mechanisms of protection and susceptibility — including sex-specific mechanisms of protection against ferroptosis, mechanisms of impaired resilience imparted by mitochondrial DNA mutations, and a role for tRNA-Asp-GTC-3′tDR in RNA autophagy — that provide new directions for diagnostic tools and therapies for acute kidney injury.
Indigenous peoples are disproportionally affected by poor kidney health outcomes globally. Here, a group of Indigenous and non-Indigenous authors provide a global overview of kidney health among Indigenous populations across different regions and its key determinants, including structural factors, and make actionable policy recommendations for addressing these health inequities.
As research on human kidney models differentiated directly from human pluripotent stem cells continues to advance rapidly, this Review examines current protocols used in the field, as well as discusses potential caveats and limitations when using these approaches for drug screening, disease modelling and tissue engineering.
In this Review, the authors outline the genetic causes and pathophysiology of monogenic syndromes associated with hypertension and discuss how common and rare variants contribute to hypertension at the population level.
Here, the authors discuss how spatial metabolomics could contribute to better understanding of cellular mechanisms in kidney health and disease, as well as the discovery of blood and urine biomarkers and drug targets for new therapies to halt kidney disease progression.
