Potential benefit of statin therapy for dyslipidemia with chronic kidney disease: Fluvastatin Renal Evaluation Trial (FRET)

Intern Med. 2011;50(12):1273-8. doi: 10.2169/internalmedicine.50.4059. Epub 2011 Jun 15.

Abstract

Background: Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients.

Aim: The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD.

Methods: In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed.

Results: After 3 months of treatment with fluvastatin, LDL-cholesterol level significantly decreased. Serum creatinine level, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), urinary liver-type fatty acid binding protein (L-FABP) level and urinary 8-hydroxydeoxyguanosine (8-OHdG) level did not change in overall patients. However, in patients with microalbuminuria (baseline UAE ≥ 30 mg/g·creatinine; n = 23), the UAE significantly decreased [2.43 ± 0.67 to 1.98 ± 0.80 log(mg/g·creatinine), p = 0.01]. In patients with high L-FABP group (baseline L-FABP ≥ 11 µg/g·creatinine; n = 18), the urinary L-FABP level was significantly decreased (1.52 ± 0.45 to 1.26 ± 0.43 µg/g·creatinine, p < 0.01). In the limited 23 patients with microalbuminuria, the L-FABP level was significantly decreased [1.20 ± 0.62 to 1.03 ± 0.49 log(µg/g·creatinine), p = 0.042], although the LDL-cholesterol level (139 ± 28 to 129 ± 23 mg/dL, p = 0.08) only showed a tendency to decrease. The 8-OHdG level also was significantly decreased (13.6 ± 9.6 to 9.8 ± 3.8 ng/g·creatinine, p = 0.043). In the overall patients, changes in the values for UAE and urinary L-FABP were not correlated with the changes in LDL-levels.

Conclusion: Fluvastatin reduces both UAE and the urinary L-FABP level, and thus, has renoprotective effects, independent of its lipid lowering effects in dyslipidemic patients with CKD.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Aged, 80 and over
  • Albuminuria / complications
  • Albuminuria / drug therapy
  • Cholesterol, LDL
  • Creatinine / blood
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / etiology*
  • Fatty Acid-Binding Proteins
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Female
  • Fluvastatin
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Indoles / therapeutic use*
  • Male
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Fluvastatin
  • 8-Hydroxy-2'-Deoxyguanosine
  • Creatinine
  • Deoxyguanosine