Novel Pathway Behind Calciphylaxis Identified
Researchers have uncovered a novel biological pathway responsible for skin lesions in a rare uremic vascular disease.
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The global burden of chronic kidney disease (CKD) is rising, with more than 800 million people affected worldwide. Vascular diseases in patients with CKD are unique and grouped as uremic vascular diseases. One of them, calciphylaxis, typically affects patients with end-stage, advanced kidney disease. It is a condition characterized by severe, painful and non-healing skin ulcers with no known cure.
For the first time, researchers from Boston University Chobanian & Avedisian School of Medicine in collaboration with the Massachusetts General Hospital, have discovered a novel biological pathway, called the IL6 pathway, central to the skin lesion initiation and progression. Blocking this pathway they believe, will likely prevent progression of the skin ulcers and resolve the pain seen in patients with calciphylaxis.
“This study reveals the presence of a pathological and harmful cycle between the fat under the skin, sweat glands and small blood vessels that keep feeding onto itself. If this cycle isn’t stopped and remains unchecked, it will lead to the skin ulcers that won’t heal. Using the specific pathway we identified, we could break this cycle and prevent the skin ulcers from getting worse,” explained corresponding author Vipul Chitalia, MD, PhD, professor of medicine.
In the study, human calciphylaxis skin and blood samples were examined for proteins and genes to analyze alterations in disease-causing mechanisms. An FDA-approved drug was then applied to see if the disease-causing pathway could be suppressed.
According to the researchers, drugs that can block this pathway are already available, safe to use and approved for other indications. “Those drugs are likely to prevent progression of the skin ulcers and resolve the pain that we see in patients with calciphylaxis. Human trials are now needed to show the benefit of those drugs.” explained co-author Jean Francis, MD, associate professor of medicine.
Reference: Napoleon MA, Yang X, Zhang Y, et al. Activation and targetability of TYMP–IL-6–TF signaling in the skin microenvironment in uremic calciphylaxis. Sci Transl Med. 2025;17(795):eadn5772. doi: 10.1126/scitranslmed.adn5772
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