REPAIR

Globally, an estimated 700 million people have kidney disease. The most common cause of death for patients with advanced CKD is cardiovascular. Half of all deaths in patients with advanced CKD are attributed to cardiovascular events. The importance of the cardiovascular disease in CKD is not only in that it is common but also in that, unlike cardiovascular events in patients without advanced CKD, there are few treatments that are known to prevent cardiovascular events in patients with advanced CKD because they are systematically excluded from RCTs.

Patients with CKD frequently have elevated markers of inflammation including TNFα, IL-1, and IL-6. The reasons for this are unclear but the epidemiologic relationship between markers of inflammation and cardiovascular events in patients with CKD is consistent with the relationship seen in patients without CKD. This suggests that inflammation plays a similarly important role in cardiovascular events in CKD.

Colchicine’s effects on cardiovascular events garnered substantial recent attention due to the publication of large trials. Colchicine is a widely available, inexpensive drug that has been used for decades to treat inflammatory disorders. Colchicine’s most recognized mechanism of action is the inhibition of tubulin which leads to down regulation of multiple inflammatory pathways. Colchicine has shown promise for cardiovascular risk reduction in patients without severe CKD, but its appropriate dosing, safety, and efficacy are uncertain in patients with severe CKD and those requiring dialysis.

The purpose of this phase-2 study is to inform the design of a large, simple RCT to evaluate the efficacy and safety of low-dose colchicine to prevent cardiovascular events in patients with advanced CKD requiring or not requiring dialysis.