Year in Review

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.

Studies in 2022 have advanced knowledge of pregnancy outcomes in kidney donors and transplant recipients as well as the long-term risks associated with hypertensive disorders of pregnancy. These findings should be used to support shared decision-making and appropriate care of women with or at risk of kidney disease.

Over the past year, trial data have emerged on therapeutic interventions in IgA nephropathy and lupus nephritis, including the effects of different doses of glucocorticoids and several novel targeted therapies. These data, in combination with the discovery of autoantibodies targeting nephrin in minimal change disease, can inform the management of immune-mediated glomerular diseases.

Kidney transplantation is the best therapy for kidney failure, but is limited by donor organ availability and the risks associated with immunosuppression. Studies in 2022 provided encouraging data about the outcomes of COVID-19 among transplant recipients, the effects of changes to organ allocation policy in the US and progress in xenotransplantation, raising hope that the organ shortage can be solved.

Inter-organ interactions are critical for maintaining homeostasis in the body but can contribute to multi-organ dysfunction. Clinical evidence indicates that kidney dysfunction contributes to remote organ dysfunction, but little is known of the underlying mechanisms. Several reports published in 2022 identified critical mediators of kidney crosstalk with distant organs.

Glucocorticoid exposure remains a major contributor to morbidity and mortality in patients with immune-mediated kidney disease. Recent clinical trials have tested novel potential therapies for these patients and showed that glucocorticoid doses can be reduced without compromising efficacy.

The dramatic increase in advocacy and scholarly work on the impact of structural racism on health inequities that began in 2020 has been sustained in the past year. In response to the call for action on these issues, the nephrology community has developed policy-based mitigation strategies and continues to examine our role in promoting health equity and justice in the care of patients with kidney disease.