New antibody may slow kidney damage
Researchers at Karolinska Institutet, Uppsala University and Northwestern University have identified a new way to protect the kidney’s blood vessels and reduce tissue damage in chronic kidney disease. The findings are published in the Journal of Clinical Investigation.
Chronic kidney disease is a growing health concern affecting around one in ten 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.
Protects the blood vessels
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 signalling 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 signalling.
Steps towards new treatment
“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 Marie 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.
Publication
TIE2 activation by antibody-clustered endogenous angiopoietin-2 prevents capillary loss and fibrosis in experimental kidney disease. Pietilä R, Marks-Hultström AM, He L, Nanavazadeh S, Quaggin SE, Betsholtz C, Jeansson M
J Clin Invest, online 15 September 2025 Sep, doi: 10.1172/JCI190286.