title: Rosuvastatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial.
abstract: BACKGROUND
  In chronic human immunodeficiency virus (HIV) infection, plasma cystatin C may be influenced by factors other than glomerular filtration rate such as inflammation. Statins may improve cystatin C by improving glomerular function or by decreasing inflammation.
  
  
  METHODS
  The Stopping Atherosclerosis and Treating Unhealthy Bone With Rosuvastatin in HIV (SATURN-HIV) trial randomized 147 patients on stable antiretroviral therapy (ART) with low-density lipoprotein cholesterol ≤130 mg/dL to blinded 10 mg daily rosuvastatin or placebo. We analyzed relationships of baseline and 0- to 24-week changes in plasma cystatin C concentration with measures of vascular disease, inflammation, and immune activation.
  
  
  RESULTS
  Median age was 46 (interquartile range, 40-53) years; 78% were male, 68% African American. Tenofovir and protease inhibitors were used in 88% and 49% of subjects, respectively. Baseline cystatin C was associated with higher carotid intima-media thickness and epicardial adipose tissue independent of age, sex, and race. Biomarkers of endothelial activation and inflammation were associated with cystatin C in a multivariable model independent of creatinine-based estimated glomerular filtration rate (eGFRcr). After 24 weeks, statin use slowed mean eGFRcr decline (1.61 vs -3.08 mL/minute/1.73 m(2) for statin vs placebo; P = .033) and decreased mean cystatin C (-0.034 mg/L vs 0.010 mg/L; P = .008). Within the statin group, changes in cystatin C correlated with changes in endothelial activation, inflammation, and T-cell activation.
  
  
  CONCLUSIONS
  Rosuvastatin 10 mg daily reduces plasma cystatin C and slows kidney function decline in HIV-infected patients on ART. Reductions in cystatin C with statin therapy correlate with reductions in inflammatory biomarkers. Relationships between cystatin C, kidney function, and cardiovascular risk in HIV may be mediated in part by inflammation. Clinical Trials Registration. NCT01218802.
authors.affiliation: Case Western Reserve University School of Medicine University Hospitals Case Medical Center.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Longenecker
authors.affiliation: Case Western Reserve University School of Medicine MetroHealth Medical Center, Cleveland.
authors.forename: Corrilynn O
authors.initials: CO
authors.lastname: Hileman
authors.affiliation: The Ohio State University School of Health and Rehabilitation Sciences, Columbus.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.affiliation: Case Western Reserve University School of Medicine University Hospitals Case Medical Center.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000517:prevention & control*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000032:analysis; D055316:Cystatin C / Q000032:analysis*; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium
keywords: HIV; cystatin C; inflammation; kidney; statin