Year in Review

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.

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.

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.

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.

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.

Over the past year, several new research insights and policy changes have advanced the field of kidney transplantation: kidney xenotransplantation has reached its first human recipients, previously under-used organs are becoming transplantable with new procurement and preservation approaches, and post-transplant care, including prevention of complications, has become safer.

In 2024, a plethora of novel therapeutic strategies for kidney disease progressed to clinical trials, including an RNA interference therapeutic, a glucagon-like peptide 1 receptor agonist, a soluble guanylate cyclase activator and an off-the-shelf, virus-specific T cell therapy. These advances herald new hope for people with kidney disease.

Progression of chronic kidney disease to kidney fibrosis is a key challenge in nephrology. Several contributions from the past year have shed light not only on the general molecular signature of human kidney fibrosis, but also on specific new mechanisms involved in its development.

Diabetic kidney disease (DKD), the most common cause of chronic kidney disease, is primarily caused by metabolic dysfunction, likely due to mitochondrial abnormalities. In 2024, several studies made important strides towards defining the molecular mechanisms that underlie the development of DKD.

Inter-organ interactions are critical for homeostasis and proper organ functioning. Several studies published in 2024 have provided insights into the mechanisms underlying reciprocal interactions of the kidney with the brain, gut and liver.

New studies have revealed a novel homeostatic clearance function for medullary macrophages, unveiled roles for innate lymphoid cells and epithelial cells in orchestrating inflammation and fibrosis, and shown that clonal haematopoiesis influences the magnitude of inflammation in response to injury. These discoveries suggest therapeutic strategies to prevent kidney dysfunction associated with ageing and injury.

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.

More than three-quarters of cases of chronic kidney disease are caused by glomerular diseases with glomerulosclerosis, including diabetic kidney disease, hypertensive nephropathy and glomerulonephritis. Studies in 2022 provided insights into the molecular mechanisms that maintain dynamic glomerular structures and the responses of specific glomerular cell types during glomerular disease.

Acute kidney injury (AKI) is a multifactorial syndrome with a complex pathophysiology including different inflammatory cells and mediators. Current research focuses on identifying key contributing pathways, determining high-risk groups, characterizing AKI sub-phenotypes and investigating strategies for therapeutic interventions.