title: Atorvastatin improves tubular status in non-diabetic patients with chronic kidney disease - placebo controlled, randomized, cross-over study.
abstract: BACKGROUND
  There is evidence that dyslipidemia is associated with chronic kidney disease (CKD) and it has been implicated in the progression of renal damage. Optimal management of dyslipidemia should therefore lead to renal benefits. A number of experimental models demonstrate a beneficial effect of statins in ameliorating renal damage. However, the exact mechanism by which statins protect against renal damage remains unclear.
  
  
  METHODS
  In a placebo-controlled, randomized, cross-over study we evaluated the influence of atorvastatin (ATO) 40 mg/day added to the renin-angiotensin-aldosterone systeme (RAAS) blockade on proteinuria and surrogate biomarkers of tubular damage or injury in 14 non-diabetic patients with proteinuria (0.4-1.8 g per 24 h) with normal or declined kidney function (eGFR 55-153 ml/min). In the eight-week run-in period, therapy using angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: ATO/washout/placebo or placebo/washout/ATO. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. The primary end point of this study was a change in proteinuria measured as 24-h urine protein excretion (DPE). Secondary end points included urine N-acetyl-β-D-glucosaminidase (NAG) and α1-microglobulin (α1m) excretion.
  
  
  RESULTS
  The ATO therapy significantly reduced urine excretion of α₁m (p=0.033) and NAG (p=0.038) as compared to placebo. There were no differences in proteinuria, blood pressure, eGFR and serum creatinine between the ATO and placebo groups.
  
  
  CONCLUSIONS
  Atorvastatin treatment is safe and improves biomarkers of tubular damage or injury in non-diabetic patients with CKD.
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Poland. mrenke@gumed.edu.pl
authors.forename: Marcin
authors.initials: M
authors.lastname: Renke
authors.forename: Leszek
authors.initials: L
authors.lastname: Tylicki
authors.forename: Przemysław
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Alexander
authors.initials: A
authors.lastname: Neuwelt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Larczyński
authors.forename: Marcin
authors.initials: M
authors.lastname: Ziętkiewicz
authors.forename: Ewa
authors.initials: E
authors.lastname: Aleksandrowicz
authors.forename: Wiesława
authors.initials: W
authors.lastname: Lysiak-Szydłowska
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D018592:Cross-Over Studies; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin