地震相关挤压综合征急性肾损伤患者尿中肾损伤标志物的变化及意义
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摘要
目的:评估地震相关挤压综合征(crush syndrome,CS)急性肾损伤透析患者尿中中性粒细胞明胶酶脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、IL-18及肾损伤分子(kidney injury molecule-1,KIM-1)的变化,以及这些指标与血肌酐、尿肌红蛋白等指标的关系,研究治疗前后肾损伤标志物的改变。方法:研究纳入16例CS急性肾损伤透析患者,12名正常对照,对10例CS患者随访14d,用ELISA方法分别测定两组尿IL-18、NGAL及KIM-1;同时测定患者尿肌酐、血肌酐、血肌红蛋白等生化指标。使用ATN-ISI'评估CS患者病情严重程度及转归。结果:与对照组比较,CS患者:血肌酐明显升高[(324.0±189.7)μmol/Lvs(72.1±15.7)μmol/L,P<0.01]、尿肌红蛋白明显升高[(593.5±381.4)ng/mlvs(8.7±1.7)ng/ml,P<0.01]。肾损伤标志物尿IL-18[(59.54±41.31)μg/gvs(22.62±17.40)μg/g,P<0.01]、尿NGAL[(1.06±1.07)μg/gvs(0.39±0.30)μg/g,P<0.05]、尿KIM-1[(1.87±1.47)μg/gvs(0.92±0.62)μg/g,P<0.05)均明显升高。Pearson分析提示尿KIM-1、尿NGAL、尿IL-18之间存在正相关,P值均小于0.05;NGAL与ATN-ISI呈正相关(r=0.65,P<0.01)。病程前后(n=10)NGAL含量分别为(0.86±0.51)μg/g、(0.78±0.64)μg/g,P>0.05,IL-18含量分别为(57.33±36.97)μg/g、(97.14±118.72)μg/g,(P>0.05),KIM-1含量分别为(1.78±1.61)μg/g、(1.77±1.55)μg/g,(P>0.05)。其中有3例患者脱离透析治疗,病程第14d其尿NGAL(1.14±0.54)μg/g,(0.37±0.23)μg/g、KIM-1(3.01±1.54)μg/g,(0.75±0.52)μg/g、IL-18(71.73±30.34)μg/g,(24.13±12.23)μg/g,均明显下降。结论:CS接受透析的患者肾损伤标志物IL-18、NGAL、KIM-1均明显升高,其中NGAL与肾脏损伤程度正相关,上述指标可随CS患者肾功能的恢复而下降。
Objective:To observe the changes of urine NGAL(neutrophil gelatinase-associated lipocalin),IL-18,and KIM-1(kidney injury molecule-1) in earthquake-caused crush syndrome(CS) patients with acute kidney injury(AKI) on continous renal replacement therapy(CRRT). Methodology:Sixteen patients with crush syndrome in Wenchuan Earthquake receiving CRRT therapy were enrolled in this research,and 10 patients were followed up for 14 days,the control were 12 healthy volunteers.The blood samples and urine samples were obtained from both groups.The urinary levels of IL-18,KIM-1 and NGAL were measured by ELISA techniques.Other parameters such as urine creatine,serum creatine,serum myoglobin,urine myoglobin,serum creatinekinase and serum potassium were measured at the same time.ATN-ISI' was applied to evaluate the severity and prognosis of AKI.Independent t-test was applied to compare the difference of age,serum creatine,urine myoglobin,urine NGAL,urine KIM-1,and urine IL-18 between the experimental group and the control.Paired t-test was applied to compare the changes of urine NGAL,KIM-1,and IL-18 between day 1 and day 14 we observed.Pearson's test was applied to study the correlation between ATN-ISI' and the urine markers of IL-18,NGAL,and KIM-1. Results:There was no difference of age(40.0±21.4 vs 34.2±6.7,P>0.05) between the CS group and the control.Serum creatine(324±189 μmol/L vs 72.1±15.7 μmol/L,P<0.01),urine myoglobin(594±381ng/ml vs 8.70±1.70ng/ml,P<0.01),urine IL-18(59.5±41.3 μg/g vs 22.62±17.40 μg/g,P<0.01),urine NGAL(1.06±1.07 μg/g vs 0.39±0.30 μg/g,P<0.05),and urine KIM-1(1.87±1.47 μg/g vs 0.92±0.62 μg/g,P<0.05) was higher in the CS group compared with the control.Pearson's test showed a positive correlation among urine KIM-1,NGAL,and IL-18,P<0.001.NGAL showed a positive correlation with ATN-ISI(r=0.65,P<0.01).Urine NGAL(0.86±0.51 μg/g,0.78±0.64 μg/g)(P>0.05),IL-18(57.3±36.9 μg/g,97.1±119 μg/g)(P>0.05),and KIM-1(1.78±1.61 μg/g,1.77±1.55 μg/g)(P>0.05) showed slight change from day 1 to day 14.3 patients have recovered from hemodialyis,in these patients the urinary NGAL(1.14±0.54 μg/g,0.37±0.23 μg/g),KIM-1(3.01±1.54 μg/g,0.75±0.52 μg/g),and IL-18(71.7±30.3 μg/g,24.1±12.2 μg/g) decreased with the concentrations close to the control on day 14. Conclusion:Urine AKI markers such as IL-18,NGAL,and KIM-1 increases in earthquake-caused crush syndrome patients with acute renal failure.Urine NGAL may predict the severity of kidney injury,these markers decrease with the recovery of kidney injury.
Objective:To observe the changes of urine NGAL(neutrophil gelatinase-associated lipocalin),IL-18,and KIM-1(kidney injury molecule-1) in earthquake-caused crush syndrome(CS) patients with acute kidney injury(AKI) on continous renal replacement therapy(CRRT). Methodology:Sixteen patients with crush syndrome in Wenchuan Earthquake receiving CRRT therapy were enrolled in this research,and 10 patients were followed up for 14 days,the control were 12 healthy volunteers.The blood samples and urine samples were obtained from both groups.The urinary levels of IL-18,KIM-1 and NGAL were measured by ELISA techniques.Other parameters such as urine creatine,serum creatine,serum myoglobin,urine myoglobin,serum creatinekinase and serum potassium were measured at the same time.ATN-ISI' was applied to evaluate the severity and prognosis of AKI.Independent t-test was applied to compare the difference of age,serum creatine,urine myoglobin,urine NGAL,urine KIM-1,and urine IL-18 between the experimental group and the control.Paired t-test was applied to compare the changes of urine NGAL,KIM-1,and IL-18 between day 1 and day 14 we observed.Pearson's test was applied to study the correlation between ATN-ISI' and the urine markers of IL-18,NGAL,and KIM-1. Results:There was no difference of age(40.0±21.4 vs 34.2±6.7,P>0.05) between the CS group and the control.Serum creatine(324±189 μmol/L vs 72.1±15.7 μmol/L,P<0.01),urine myoglobin(594±381ng/ml vs 8.70±1.70ng/ml,P<0.01),urine IL-18(59.5±41.3 μg/g vs 22.62±17.40 μg/g,P<0.01),urine NGAL(1.06±1.07 μg/g vs 0.39±0.30 μg/g,P<0.05),and urine KIM-1(1.87±1.47 μg/g vs 0.92±0.62 μg/g,P<0.05) was higher in the CS group compared with the control.Pearson's test showed a positive correlation among urine KIM-1,NGAL,and IL-18,P<0.001.NGAL showed a positive correlation with ATN-ISI(r=0.65,P<0.01).Urine NGAL(0.86±0.51 μg/g,0.78±0.64 μg/g)(P>0.05),IL-18(57.3±36.9 μg/g,97.1±119 μg/g)(P>0.05),and KIM-1(1.78±1.61 μg/g,1.77±1.55 μg/g)(P>0.05) showed slight change from day 1 to day 14.3 patients have recovered from hemodialyis,in these patients the urinary NGAL(1.14±0.54 μg/g,0.37±0.23 μg/g),KIM-1(3.01±1.54 μg/g,0.75±0.52 μg/g),and IL-18(71.7±30.3 μg/g,24.1±12.2 μg/g) decreased with the concentrations close to the control on day 14. Conclusion:Urine AKI markers such as IL-18,NGAL,and KIM-1 increases in earthquake-caused crush syndrome patients with acute renal failure.Urine NGAL may predict the severity of kidney injury,these markers decrease with the recovery of kidney injury.
引文
1梁培禾,靳风烁.灾难和事故的创伤救治,北京:人民卫生出版社.2005:388-389.
2 LianoF,Pascual J,Garcia-Martin F,et al.Prognosis of acute tubular necro-sis:an extended prospectively contrasted study.Nephron,1993,63:21-31.
3 Mishra J,Mori K,Ma Q,et al.Amelioration of ischemic acute renalinjury by neutrophil gelatinase-associated lipocalin.J Am SocNephrol,2004,15(12):3073-3082.
4 Mori K,Lee HT,Rapoport D,et al.Endocytic delivery of lipocalin-siderophoreiron complex rescues the kidney from ischemia-reperfusioninjury.J Clin Invest,2005,115(3):610-621.
5 Ichimura T,Bonventre JV,Bailly V,et al.Kidney injury molecule-1(KIM-1),a putative epithelial cell adhesion molecule containing anovel immunoglobulin domain,is up-regulated in renal cells after inju-ry.J Biol Chem,1998,273(7):4135-4142.
6 Vaidya VS,Ramirez V,Ichimura T,et al.Urinary kidney injury molecule-1:a sensitive quantitative biomarker for early detection of kidney tubularinjury.Am J Physiol Renal Physiol,2006,290(2):F517-F529.
7 Han WK,Bailly V,Abichandani R,et al.Kidney injury molecule-1(KIM-1):a novel biomarker for human renal proximal tubule injury.Kidney Int,2002,62(1):237-244.
8 Van Timmeren MM,Bakker SJ,Vaidya VS,et al.Tubular kidney in-jury molecule-1 in protein-overload nephropathy.Am J Physiol RenalPhysiol,2006,291(2):F456-F464.
9 Ichimura T,Hung CC,Yang SA,et al.Kidney injury molecule-1:atissue and urinary biomarker for nephrotoxicant-induced renal injury.Am J Physiol Renal Physiol,2003,286(3):552-563.
10张文贤,张训,侯凡凡,等.两种评价急性肾衰竭患者预后及肾脏转归积分模型的比较.中华内科杂志,2002,41:769-772.
2 LianoF,Pascual J,Garcia-Martin F,et al.Prognosis of acute tubular necro-sis:an extended prospectively contrasted study.Nephron,1993,63:21-31.
3 Mishra J,Mori K,Ma Q,et al.Amelioration of ischemic acute renalinjury by neutrophil gelatinase-associated lipocalin.J Am SocNephrol,2004,15(12):3073-3082.
4 Mori K,Lee HT,Rapoport D,et al.Endocytic delivery of lipocalin-siderophoreiron complex rescues the kidney from ischemia-reperfusioninjury.J Clin Invest,2005,115(3):610-621.
5 Ichimura T,Bonventre JV,Bailly V,et al.Kidney injury molecule-1(KIM-1),a putative epithelial cell adhesion molecule containing anovel immunoglobulin domain,is up-regulated in renal cells after inju-ry.J Biol Chem,1998,273(7):4135-4142.
6 Vaidya VS,Ramirez V,Ichimura T,et al.Urinary kidney injury molecule-1:a sensitive quantitative biomarker for early detection of kidney tubularinjury.Am J Physiol Renal Physiol,2006,290(2):F517-F529.
7 Han WK,Bailly V,Abichandani R,et al.Kidney injury molecule-1(KIM-1):a novel biomarker for human renal proximal tubule injury.Kidney Int,2002,62(1):237-244.
8 Van Timmeren MM,Bakker SJ,Vaidya VS,et al.Tubular kidney in-jury molecule-1 in protein-overload nephropathy.Am J Physiol RenalPhysiol,2006,291(2):F456-F464.
9 Ichimura T,Hung CC,Yang SA,et al.Kidney injury molecule-1:atissue and urinary biomarker for nephrotoxicant-induced renal injury.Am J Physiol Renal Physiol,2003,286(3):552-563.
10张文贤,张训,侯凡凡,等.两种评价急性肾衰竭患者预后及肾脏转归积分模型的比较.中华内科杂志,2002,41:769-772.
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