Department of Medicine and Transplantation, Ospedali Riuniti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Nephron Clin Pract. 2010;115(2):c154-60. doi: 10.1159/000312879. Epub 2010 Apr 21.
BACKGROUND/AIMS: Nephrotoxicity is the major limitation to cisplatin therapy for solid tumors. We aimed at evaluating whether early increases in serum/urine levels of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage and regeneration, predict cisplatin-induced acute kidney injury (AKI).
We compared changes in serum creatinine and serum/urine NGAL levels (ELISA assay) at 1 and 4 h and 1, 2, 3, 7 and 15 days after cisplatin infusion (70-80 mg/m(2)) versus baseline in 12 consecutive cancer patients (cases) with AKI (>25% serum creatinine increase vs. baseline) and 12 consecutive controls without AKI.
Baseline characteristics and posttreatment serum NGAL levels were similar in both groups. Urinary NGAL levels increased significantly more in cases than in controls at 1, 2, 3 and 15 days after cisplatin. The NGAL increase preceded AKI by 4.5 days and the NGAL increase at day 2 after cisplatin independently predicted AKI (p < 0.05). Six cases with residual kidney dysfunction at 15 days showed a trend to earlier and higher increase in urinary NGAL levels compared to cases with renal function recovery.
An early increase in urinary NGAL excretion may help in identifying patients at risk of cisplatin-induced AKI who might benefit from innovative treatments to prevent cisplatin nephrotoxicity.
背景/目的:肾毒性是顺铂治疗实体瘤的主要限制因素。我们旨在评估血清/尿液中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平的早期升高是否可以预测顺铂引起的急性肾损伤(AKI)。
我们比较了 12 例 AKI(与基线相比血清肌酐增加>25%)患者(病例)和 12 例无 AKI 患者(对照组)在顺铂输注(70-80mg/m2)后 1、4 小时和 1、2、3、7、15 天的血清肌酐和血清/尿液 NGAL 水平(ELISA 法)的变化与基线相比。
两组患者的基线特征和治疗后血清 NGAL 水平相似。与对照组相比,病例组在顺铂治疗后 1、2、3 和 15 天尿液 NGAL 水平显著升高。NGAL 升高比 AKI 早 4.5 天,顺铂治疗后第 2 天的 NGAL 升高可独立预测 AKI(p<0.05)。15 天时肾功能仍有障碍的 6 例患者与肾功能恢复的患者相比,尿液 NGAL 水平的升高更早、更高,呈趋势性。
尿液 NGAL 排泄的早期增加可能有助于识别发生顺铂引起的 AKI 的风险患者,这些患者可能受益于预防顺铂肾毒性的创新治疗。