Study Finds Enzymatic Pathway Potential Treatment Target for Blood Clots in Patients With Chronic Kidney Disease

Investigators have identified a novel signaling pathway and enzyme that may further the understanding of blood clot formation in patients with chronic kidney disease (CKD), according to a study published in the Journal of the American Society of Nephrology. The investigators said this pathway may ultimately be targetable for therapy.

“We have shown for the first time that a specific enzymatic pathway is altered in CKD patients,” said Vipul Chitalia, MD, PhD, associate professor of medicine at Boston University School of Medicine, in a press release. “This pathway is regulated by an enzyme called Indoleamine 2,3-dioxygenase (IDO), which converts tryptophan amino acid to kynurenine, a potent pro-thrombotic metabolite in CKD patients. IDO1 can now be targeted as a potential treatment option.”

Following a vascular procedure, patients with CKD are at higher risk of thrombosis than patients with normal kidney function. This complication could result in potentially fatal adverse events, including myocardial ischemia. Investigators have previously discovered metabolites (uremic solutes/toxins) in the blood of patients with CKD act as drivers of thrombosis. The current study from the same investigators has uncovered an important mediator of thrombosis for these patients.

According to the investigators, the antithrombotics currently approved by the FDA do not work efficiently in patients with CKD, as they do not target the pathways specific to the disease. Further, these agents can place patients at a higher risk of bleeding, according to the study authors.

“Therefore, a safe and effective antithrombotic for CKD patients is imminent,” Chitalia said in the release. “Addressing this huge unmet clinical need, our study defines a novel therapeutic target for heightened risk of thrombosis in CKD patients.”

IDO-1 inhibitors are currently in clinical trials for other conditions. The investigators are hopeful that these same inhibitors can be repurposed in order to prevent thrombotic complications in patients with CKD.

REFERENCE

BU study finds novel pathway, enzyme responsible for thrombosis in patients with chronic kidney disease [news release]. EurekAlert; November 1, 2021. Accessed November 2, 2021. https://www.eurekalert.org/news-releases/933345