Evolocumab In Advanced Chronic Kidney Disease Trial

Inclusion Criteria: * CKD Stage 4-5 defined as * eGFR ≤30 mL/min/1.73m2 on screening lab OR * Treatment with maintenance hemodialysis for at least 30 days prior to screening * LDL ≥70 mg/dL and * Treatment with maximal tolerated doses of a statin OR * Statin intolerance defined as any history of intolerance or allergy to ≥1 statin * Age 40-80 years * Individuals ≤60 years old are required to have ≥1 of the following cardiovascular risk factors: * History of CV disease * History of peripheral vascular disease * Diabetes * Smoking * Baseline LDL ≥160 mg/dL * Macroalbuminuria (albumin to creatinine ratio ≥300 mg/g on spot sample) Exclusion Criteria: * Age \>80 years * Expected survival \< 1 year * Transplant expected within \< 1 year * Active liver disease (history of cirrhosis, ALT or AST \> 2x ULN) * CPK \> 5x ULN at screening * Malignancy within 5 years except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma * Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period * Currently enrolled in another interventional study * Female subject who has not used at least (1) effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal. * Effective measures of birth control include surgical sterilization, barrier methods, hormonal contraceptives and intrauterine devices. * Pregnant or breast-feeding subjects * Known sensitivity or intolerance to study medications The following additional criteria will be utilized to exclude individuals from participating in the PET substudy: * Severe asthma or obstructive lung disease defined by * Hospitalization for asthma or obstructive lung disease within 8 weeks * Use of oral steroids for lung disease within 8 weeks * Chronic oxygen therapy * Use of rescue inhalers ≥three times weekly in the previous 4 weeks * History of seizures * Second or third-degree AV block, unless a functioning pacemaker is present * Sinus node dysfunction unless a functioning pacemaker is present