Summary
Kidney disease is a common problem among people with type 1 diabetes and can lead to disability, dialysis, and early death. Inflammation plays a key role in the development of kidney disease in type 1 diabetes and targeting leukotrienes, inflammatory chemicals the body releases in response to allergic reactions, may represent a promising therapy to slow the progression of diabetic kidney disease. The current proposal will investigate whether montelukast, a leukotriene blocker, lowers increased levels of protein in the urine (an early marker of diabetic kidney disease), and improves kidney and cardiovascular function in people with type 1 diabetes and kidney disease.
Eligibility Criteria
Age Range: 18 years to 80 years
Inclusion Criteria:
* Age 18-80 years
* Type 1 diabetes for at least 5 years
* Urine albumin to creatinine ratio 30-5000 mg/g on first morning void
* eGFR 30-89 ml/min/1.73m2 at time of screening
* Blood pressure \<140/90 mm Hg prior to randomization
* Use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker with stable dose for 4 weeks
* BMI \< 40 kg/m2 (FMDBA measurements can be inaccurate in severely obese patients).
* Stable anti-hypertensive regimen for at least one month prior to randomization
* Stable regimen of insulin delivery, i.e. automated insulin delivery (AID) system or multiple daily injections) 4 weeks prior to randomization
* Sedentary or recreationally active (≤2 days of vigorous aerobic exercise as vigorous exercise may affect vascular function measurements)
* Able to provide consent
Exclusion Criteria:
* Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year
* Uncontrolled hypertension
* Factors judged to limit adherence to interventions
* Anticipated initiation of dialysis or kidney transplantation within 6 months
* Current participation in another research study
* Pregnancy or planning to become pregnant or currently breastfeeding
* Allergy to aspirin
* Severe hepatic impairment (Child-Pugh Class C)
* History of major psychiatric disorder
* Use of inhaled or systemic corticosteroids or long-acting beta agonists (higher risk of neuropsychiatric reaction)
* Penicillin allergy
* Iodine allergy
* Shellfish allergy
* Current use of phenobarbital, rifampin or carbamazepine