Study finds experimental antibody may reduce fibrosis in chronic kidney disease

by Karin Vikström, Karolinska Institutet

edited by Lisa Lock, reviewed by Andrew Zinin

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Credit: Journal of Clinical Investigation (2025). DOI: 10.1172/JCI190286

Chronic kidney disease is a growing health concern affecting about 1 in 10 Swedes. The condition involves a gradual decline in kidney function, which can lead to the need for dialysis or transplantation.

A new study from Karolinska Institutet, Uppsala University and Northwestern University now shows that an experimental antibody can protect the kidney’s blood vessels and reduce harmful scarring, known as fibrosis. The work is published in the Journal of Clinical Investigation.

The researchers examined how activation of a receptor on the surface of blood vessels, called TIE2, influences disease progression. By using a specific antibody, ABTAA, they were able to stimulate TIE2 and thereby protect the blood vessels in the kidney. The antibody works by binding to a protein that normally inhibits TIE2, converting it into an activator.

“By protecting the vessels, we were also able to preserve the kidney’s microenvironment and block the signaling pathways that drive fibrosis,” says Marie Jeansson from the Department of Medicine, Huddinge, one of the researchers behind the study.

The results are based on preclinical models and show that ABTAA not only reduces damage to blood vessels, but also affects other parts of the kidney. An important discovery is that damaged blood vessels do not directly transform into other cell types, as previously assumed. Instead, another cell type in the kidney is influenced to secrete substances that promote fibrosis. By activating TIE2, the researchers were able to reduce this signaling.

“Our findings suggest that TIE2 activation with ABTAA could be developed into a new treatment strategy for chronic kidney disease. This is an area where treatment options are still very limited, and progress could eventually have a major impact for patients,” says Jeansson.

The study provides new insights into how fibrosis develops in the kidney and highlights the role of blood vessels as a potential new target for treatment. The next step will be to investigate whether the results can be translated to humans.

More information: Riikka Pietilä et al, TIE2 activation by antibody-clustered endogenous angiopoietin-2 prevents capillary loss and fibrosis in experimental kidney disease, Journal of Clinical Investigation (2025). DOI: 10.1172/JCI190286

Journal information: Journal of Clinical Investigation
Provided by Karolinska Institutet

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