title: Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post hoc analysis of the LORD trial.
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are biomarkers of kidney injury and function, respectively. This study assessed whether plasma NGAL and/or serum cystatin C predicted baseline estimated glomerular filtration rate (eGFR) and urinary protein excretion, rate of change of eGFR and urinary protein excretion and whether atorvastatin influenced changes in these biomarkers in patients with chronic kidney disease (CKD).
  
  
  METHODS
  This is a post hoc analysis of the Lipid Lowering and Onset of Renal Disease trial, a randomized double-blind, placebo-controlled trial where 88 patients with Stages 2-4 CKD received atorvastatin 10 mg/day (48) or placebo (40). Stored blood samples were analysed for NGAL and cystatin C at baseline and a mean of 1.5 and 2.9 years later. Serum creatinine and Modification of Diet in Renal Disease (MDRD) eGFR were obtained three monthly.
  
  
  RESULTS
  There were negative associations between NGAL and cystatin C and eGFR (P = 0.025 and P < 0.001, respectively) at all time points. There were no associations between baseline NGAL and cystatin C and rate of change of eGFR (P = 0.44 and P = 0.49, respectively). Baseline NGAL but not cystatin C (P = 0.043 and P = 0.35, respectively) predicted rate of change of urinary protein excretion. In atorvastatin-treated patients, NGAL decreased (mean, -7.4 ng/mL/year; SD 128.4), whereas it increased in the placebo group [mean, 4.6 ng/mL/year; SD 56.6), the difference being statistically significant (P = 0.049).
  
  
  CONCLUSIONS
  NGAL is a biomarker of existing CKD but did not predict CKD progression. Atorvastatin reduced plasma NGAL but the significance and mechanisms require further investigation. Atorvastatin had no significant effect on cystatin C.
authors.affiliation: Renal Medicine Department, Royal Brisbane and Women’s Hospital, Brisbane, Australia. r.fassett@uq.edu.au
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fassett
authors.forename: Iain K
authors.initials: IK
authors.lastname: Robertson
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Ball
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Geraghty
authors.forename: John W
authors.initials: JW
authors.lastname: Cardinal
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
mesh_terms: D000209:Acute-Phase Proteins; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000188:drug therapy*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood*; D011758:Pyrroles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D000924:Anticholesteremic Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D006538:Heptanoic Acids; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D011758:Pyrroles; D000069059:Atorvastatin