Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine

Eligibility Criteria

• * Age 21 years to 80 years (inclusive)
• * eGFR of 15 to 75 mL/min per 1.73 m2
• * Urine albumin-to-creatinine ratio of greater than 30 mg/g
• * Use of maximally tolerated doses of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if urine albumin-to-creatinine ratio greater than 300 mg-g
• * Use of a sodium-glucose co-transporter-2 inhibitor if indicated in the opinion of the participant's primary clinician
• * Willing and able to provide written informed consent and to adhere to the study protocol
• 1. History of intolerance or allergy to colchicine
• 2. Hospitalization for any reason within the previous 30 days
• 3. Acute condition that requires emergent treatment in the opinion of a physician investigator
• 4. Stage C or D heart failure according to ACC-AHA criteria77
• 5. Left ventricular ejection fraction less than 40%
• 6. Symptomatic valvular heart disease
• 7. Congenital heart disease (corrected or uncorrected)
• 8. History of orthotopic heart transplant
• 9. Kidney failure, defined as kidney transplant recipient or requirement for hemodialysis or peritoneal dialysis
• 10. Worsening kidney function or acute kidney injury, defined as an increase in serum creatinine of greater than 0.3 mg/dL in the previous 30 days or 50% within the previous 7 days
• 11. Use of immunosuppressive or anti-inflammatory medications within the previous 30 days, with the exception of less than 5 days of non-steroidal anti-inflammatory drugs or corticosteroids for acute pain or other acute conditions that have since fully resolved provided that the last dose of non-steroid anti-inflammatory drug was at least 7 days before enrollment
• 12. Familial Mediterranean Fever, gout (unless no flare within the previous 12 months), pericarditis or other indications for colchicine treatment
• 13. Use of systemic antimicrobial therapy within the previous 30 days or active infection
• 14. History of respiratory illness that, in the opinion of a physician investigator, may increase the risk of pneumonia
• 15. Surgery within the previous 30 days or surgery planned to occur within the expected study period
• 16. Current malignancy or receipt of treatment for malignancy within the previous 1 year
• 17. Frailty or life-expectancy shortened by comorbidity such as cancer that would increase the participant's risk in the opinion of a physician investigator
• 18. Neutrophil count \< 2,000 cells/mm3
• 19. Platelet count \< 50,000 cells/mm3
• 20. Concomitant use of a P-gp inhibitor (e.g., cyclosporine, ranolazine, digoxin) and/or moderate-strong CYP3A4 inhibitor (e.g., clarithromycin, indinavir, itraconazole, ritonavir, nefazodone, diltiazem, verapamil, grapefruit juice, fluconazole)
• 21. Medications that may cause myopathy or rhabdomyolysis (i.e., simvastatin, gemfibrozil, fenofibrate) , a creatine kinase level after the run-in period that exceeds the upper limit of the normal laboratory reference range (if baseline was below the upper limit) or that increases by 50% or more from pre- to post-run-in
• 22. Moderate-severe hepatic disease (Child-Pugh B or C)
• 23. Pregnant or unwilling/unable to assure appropriate contraception
• 24. Breastfeeding