title: Effects of lipid-lowering therapy with rosuvastatin on kidney function and oxidative stress in patients with diabetic nephropathy.
abstract: OBJECTIVE
  We aimed to assess the effects of rosuvastatin treatment on lipid levels, a biomarker of oxidative stress, albuminuria, and kidney function in patients with diabetic nephropathy.
  
  
  METHODS
  We conducted a prospective, open-label, parallel group, controlled study of 104 patients with diabetic nephropathy, low-density lipoprotein cholesterol (LDL-C) levels of > 120 mg/dL, and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors. Patients were randomly assigned to two groups: the rosuvastatin group (n = 52; 2.5 mg/day rosuvastatin, increased to 10 mg/day) and the control group (n = 52; no rosuvastatin administered). We determined the efficacy of rosuvastatin by monitoring serum lipid profiles, high sensitivity C-reactive protein (hs-CRP), malondialdehyde-modified LDL (MDA-LDL), and cystatin C levels. In addition, urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) levels were measured before and 6 months after rosuvastatin was added to the treatment.
  
  
  RESULTS
  Rosuvastatin effectively reduced total cholesterol, LDL-C, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C) levels, and the LDL-C/ HDL-C ratio in the rosuvastatin group. These parameters remained unchanged in patients who were not treated with rosuvastatin. Although there was no significant change in the estimated glomerular filtration rate level, serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group. In addition, rosuvastatin significantly reduced hs-CRP and MDA-LDL levels. Moreover, urinary 8-OHdG and L-FABP levels at baseline (13.5±5.1 and 41.7±26.1 ng/mgCr, respectively) decreased significantly at 6 months (11.5±4.0 and 26.9±13.4 ng/mgCr, respectively), and there was a significant correlation (r = 0.48, p < 0.01). Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use (p = 0.0006, R(2)= 0.53).
  
  
  CONCLUSIONS
  Rosuvastatin administration reduced albuminuria, oxidative stress, and serum cystatin C levels, independent of blood pressure and lipid levels.
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. abe.masanori@nihon-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Noriaki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Okada
authors.forename: Shiro
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D055316:Cystatin C / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D038321:Glycemic Index; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy*; D007677:Kidney Function Tests; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D055316:Cystatin C; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein