阿托伐他汀对慢性肾脏病患者 NGAL 和胱抑素 C 的影响：LORE 试验的事后分析。

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

机构信息

Renal Medicine Department, Royal Brisbane and Women’s Hospital, Brisbane, Australia.

出版信息

Nephrol Dial Transplant. 2012 Jan;27(1):182-9. doi: 10.1093/ndt/gfr193. Epub 2011 May 4.

DOI:10.1093/ndt/gfr193

PMID:21543653

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.

摘要

背景

中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和胱抑素 C 分别是肾脏损伤和功能的生物标志物。本研究评估了血浆 NGAL 和/或血清胱抑素 C 是否可以预测慢性肾脏病（CKD）患者的基线估算肾小球滤过率（eGFR）和尿蛋白排泄率、eGFR 和尿蛋白排泄率的变化率，以及阿托伐他汀是否会影响这些生物标志物的变化。

方法

这是降脂和肾脏疾病发病研究（Lipid Lowering and Onset of Renal Disease trial）的事后分析，这是一项随机、双盲、安慰剂对照试验，纳入了 88 名处于 2-4 期 CKD 的患者，分别接受阿托伐他汀 10 mg/天（48 例）或安慰剂（40 例）治疗。在基线时以及平均 1.5 年和 2.9 年后，对储存的血液样本进行 NGAL 和胱抑素 C 分析。每三个月获取一次血清肌酐和肾脏病饮食改良试验（Modification of Diet in Renal Disease，MDRD）eGFR。

结果

在所有时间点，NGAL 和胱抑素 C 与 eGFR 均呈负相关（P=0.025 和 P<0.001）。基线时 NGAL 和胱抑素 C 与 eGFR 的变化率均无相关性（P=0.44 和 P=0.49）。基线时 NGAL 但不是胱抑素 C 可预测尿蛋白排泄率的变化率（P=0.043 和 P=0.35）。在阿托伐他汀治疗组，NGAL 下降（平均下降 7.4ng/mL/年；SD 128.4），而在安慰剂组则升高（平均升高 4.6ng/mL/年；SD 56.6），两组差异有统计学意义（P=0.049）。