News & Views

Dialysis is among the most cost-intensive health services available; however, its availability is often shaped by competing interests among providers, payers, industry and patients. Thailand’s experience in aligning these interests offers valuable lessons for countries that are striving to expand equitable kidney care within limited fiscal space and progress towards universal health coverage.

Standard treatments to reduce cardiovascular risk, including mineralocorticoid receptor antagonists, have not lowered the high cardiovascular mortality and morbidity of patients on long-term haemodialysis. Future research should focus on targeting inflammatory pathways that are activated when blood interacts with dialysis membranes.

A new study reports that in 2010–2019, mortality owing to non-communicable diseases continued to decline in the majority of countries worldwide. However, the data also highlight major disparities between countries and a widespread slowing of progress in reducing mortality compared to the previous decade.

Anaemia is a frequent complication of chronic kidney disease (CKD) that is associated with reduced quality of life and adverse clinical outcomes. A new analysis suggests that the global burden of anaemia in CKD will rise substantially in the next 25 years.

Social and environmental exposures are strong drivers of health inequity and adverse health outcomes. However, data from studies that examine the longitudinal effect of social and environmental exposure burdens on kidney disease outcomes are limited. The environmental justice index–social environmental ranking, although imperfect, provides an important tool to address this gap in knowledge.

Advanced instrumentation and rapid computation are generating ever more data on human genetics, epigenetics, transcriptomics, proteomics and metabolomics, posing challenges of integration and interpretation. New research has applied rigorous statistical analyses to genetic variations identified in patients with kidney disease to find drivers of (patho)physiological differences in urine and plasma metabolomes.

Based on genome-wide association study data from 2.2 million individuals, a functional prioritization scorecard integrates classical omics with allele-specific gene expression, chromatin accessibility and gene regulatory circuits in kidney tissues and specific cell types. This approach prioritized 601 kidney function-related genes, including genes associated with nephropathy in mice and humans.

Transdermal detection of fluorescent markers has potential to provide point-of-care measurement of glomerular filtration rate. However, validation of proposed approaches and confirmation of their clinical utility should be required ahead of their adoption in the clinic.

Innate immune memory represents a barrier to successful kidney transplantation. The discovery that uraemic toxins in people with kidney failure induce trained immunity suggests that, as chronic kidney disease progresses, long-lived memory macrophages promote systemic chronic inflammation, which could contribute to organ transplant rejection.

New data demonstrate that in people with HIV infection, transplantation outcomes with HIV-positive donor kidneys are not inferior to those with HIV-negative donor kidneys and donor-derived HIV strains do not persist in the recipients. This approach should be standard of care for kidney transplantation in people living with HIV.

A turning point in the treatment of IgA nephropathy has been marked by several new publications that describe promising outcomes associated with the targeting of key pathogenic disease processes, including the production of galactose-deficient IgA1 and IgA-containing immune complexes, complement and endothelin system activation.

Sodium–glucose co-transporter 2 inhibitors have revolutionized the management of chronic kidney disease. However, long-term data regarding their use are lacking. The post-trial follow-up study to EMPA-KIDNEY provides several insights into how the effects of these powerful medications might be optimized, but several key questions remain unanswered.

A new study demonstrates that anti-nephrin autoantibodies are not merely markers but also actively contribute to the pathogenesis of minimal change disease and primary focal segmental glomerulosclerosis. This insight not only provides a non-invasive diagnostic alternative to kidney biopsies, but also suggests potential for novel targeted therapies.

Glucagon-like peptide 1 receptor agonists improve glucose control, promote weight loss and reduce the risk of major cardiovascular events in people with type 2 diabetes mellitus. The FLOW study now provides unequivocal evidence of kidney protective effects with semaglutide in adults with type 2 diabetes mellitus and chronic kidney disease.

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.

A new study describes the development of proteomics-based ageing clocks that calculate the biological age of specific organs and define features of extreme ageing associated with age-related diseases. Their findings support the notion that plasma proteins can be used to monitor the ageing rates of specific organs and disease progression.

Improved understanding of the interrelated nature of cardiovascular, kidney and metabolic (CKM) health, the development of novel risk prediction equations, and the availability of powerful new therapies provide an opportunity to change the course of CKM health. Achieving such change at a population level will require additional advances to deliver equitable interdisciplinary care.

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.

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.

A recent study reports that adenosine A2A receptor-mediated lymphangiogenesis increases lymphatic clearance of excess Na⁺ from the skin and reduces blood pressure, whereas impairment of this process leads to salt-sensitive hypertension. These findings raise intriguing physiological questions regarding the relationships among sodium, water and blood pressure.