Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)

Inclusion Criteria:

- Age 18-80 years

- CKD stage III or IV (eGFR with the 4-variable Modified Diet Renal Disease (MDRD)
prediction equation: 15-60 mL/min/1.73m2; stable renal function in the past 3 months)

- An elevated high sensitivity C-reactive protein (hs-CRP) of > 2.0 mg/L and <30 mg/L
on at least 2 consecutive weekly determinations

- Urine protein excretion < 5.0 g/24h estimated by a spot urine protein/creatinine
ratio

- Ability to provide informed consent

Exclusion Criteria:

- Patients with advanced CKD requiring chronic dialysis

- Active infection (chronic or acute (within 3 months) or antibiotic therapy (w/in 1
mo); history of recurrent infection

- Significant co-morbid conditions that lead the investigator to conclude that life
expectancy is less than 1 year

- Expected to undergo living related transplant in next 6 months

- History of severe congestive heart failure (i.e., EF < 35%)

- Hospitalization in the past month

- Severe arthritis, lupus, inflammatory bowel disease, asthma or other disease(s) or
medical condition(s) that, in the opinion of the investigator, could interfere with
hsCRP or immune function

- Immunosuppressant agents such as cyclosporine, tacrolimus, azathioprine, etanercept,
infliximab, adalimumab, anakinra or long-term oral glucocorticoids taken in past 12
months

- Known malignancy

- HIV, active, chronic hepatitis B as evidenced by HBsAg positive and HBsAb negative,
or hepatitis C positive

- Woman who are pregnant, nursing or planning to become pregnant

- Body mass index (BMI) >40 kg/m2

- Warfarin use (or other cytochrome P (CYP)450 substrates with a narrow therapeutic
index) [ok if do not participate in endothelial cell collection]

- Taking medication(s) that interact with agents administered during experimental
sessions (e.g., sildenafil interacts with nitroglycerin)

- Currently receiving or planning to receive live or inactivated vaccines

- Alcohol dependence or abuse

- Subjects at risk for tuberculosis (TB). Specifically, subjects with:

- Current clinical, radiographic or laboratory evidence of active TB at screening or
latent TB that has not been previously treated

- A history of active TB within the last 3 years even if it was treated.

- A history of active TB greater than 3 years ago unless there is documentation that
the prior anti-TB treatment was appropriate in duration and type.

- Therapy for latent TB which has not been completed as per local guidelines.