Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post-hoc analysis of the LORD Trial

Background and objectives 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 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 CKD. Design, setting, participants, and measurements This is a post-hoc analysis of the Lipid Lowering and Onset of Renal Disease (LORD) 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 2.9 years later. Serum creatinine and MDRD eGFR were obtained from the LORD trial data. Results There was a strong negative association between baseline NGAL levels and baseline eGFR (P<0.001), but no association between baseline NGAL level and rate of change of eGFR (P=0.44). Baseline cystatin C was not associated with rate of change of eGFR. In atorvastatin-treated patients, serum 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). There was a strong negative association between baseline cystatin C and baseline eGFR (P<0.001). Urinary protein excretion was predicted by NGAL but not cystatin C. Conclusions NGAL is a biomarker of existing CKD but did not predict CKD progression. Atorvastatin reduced plasma NGAL but the significance and mechanism require further investigation. Atorvastatin had no significant effect on cystatin C.