血清胱抑素C与血清肌酐在急性肾损伤患者GFR评估中的比较研究
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摘要
目的
探讨血清胱抑素C(SCysC)作为肾小球滤过率标志物在诊断急性肾损伤中的价值。
方法
本研究共纳入ICU患者共46例,男36例(78%),女10例(22%),年龄( 56.2土18(20-80))岁。对每例入住ICU的患者于入院当日采静脉血1.5 mL保存,测血清肌酐作为基线资料。此后,每日检测血清肌酐,并密切观察尿量变化。对按标准诊断为AKI的患者,每日清晨8:00采静脉血1.5 mL,3000转离心10分钟后留取血清并保存于-70℃冰箱,直至患者出院、转科、行RRT治疗或死亡。将肌酐值最大日的标本集中测量SCysC。采用酶法测定血清肌酐。采用酶免法(ELISA)测SCysC。肌酐清除率(Ccr)采用Cockroft--Gault公式计算,以此作为GFR的估计值。应用SPSS 13.0统计软件对数据进行统计处理。计量资料以( x土s)表示,两组均数的比较用t检验;计数资料用百分率表示,应用X2 (卡方)检验;正常人中各项指标的95%参考值范围表示为( x土2s);相关关系采用Pearson相关系数和一元线性回归分析;运用ROC分析曲线评价SCysC诊断AFR的准确性、敏感性和特异性,并且寻找SCysC的最佳截断值;应用多元线性回归分析影响SCysC浓度的因素。
结果
发生急性肾损伤的46例患者处于1,2,3期的患者分别为19,11和16例。71名健康人作为对照组。在急性肾损伤患者中SCysC较正常组明显升高(P<0.01);46例AKI患者血清SCysC与Scr成显著线性相关,相关系数(r=0.877,p<0.01); 46例AKI患者( SCysC ) -1与eGFR成显著线性相关,相关系数R=0.924,p<0.01,回归方程eGFR=-32.15+150.003(SCysC)-1或(SCysC)-1 =0.24+0.006eGFR。以患者Scr升高1.5倍作为AKI诊断标准,由ROC曲线可以看出SCysC在AKI的诊断中,曲线下面积为0.949,95%可信区间为(0.890-1.008,p<0.01)。以估算的eGFR<=60 ml/min/1.732作为AKI的诊断标准,由ROC曲线可以看出SCysC在AKI的诊断中,曲线下面积为0.970,95%可信区间为(0.964-1.014,p<0.01) ,最佳截断值为1.832 mg/l,敏感性和特异性分别为97.4%和100%。以此标准由ROC曲线可以看出Scr在AKI的诊断中,曲线下面积为0.925,95%可信区间为(0.934-1.022,p<0.01),最佳截断值为123.5μmol/l,敏感性和特异性分别为93.4%和100%,两者AUC差别有统计学意义。以估算的eGFR<=60 ml/min/1.732作为AKI的诊断标准,将第1期患者比较发现Scr在AKI的诊断中,曲线下面积为0.864,95%可信区间(0.791-1.066,p<0.01), SCysC在AKI的诊断中,曲线下面积为0.932,95%可信区间为(0.885-1.044,p<0.01),两者比较有显著差异性。以最佳截断值评价诊断效能,发现SCysC准确性(88.7%v82%)、阳性及阴性预测值较Scr高,两者总体敏感性(Sen)、特异性(Spe)无明显差异。根据求得的正常人群各项检测指标,采用参考值范围上限(SCysC为1.7 mg/l,Scr为133μmol/l )为截断值,求得两指标的灵敏度,发现所有患者CysC(95.7%)及第一期患者CysC(89.5%)的灵敏度要明显优于所有患者Scr (82.6%)及第一期患者Scr(57.9%)。SCysC浓度的变化主要受Ccr的影响,而与患者的年龄、性别、体重、血糖、血红蛋白、总胆红素、血清蛋白、血前白蛋白等因素无关。
结论
在ICU内SCysC可以作为急性肾损伤患者GFR的内源性标志物,SCysC能较Scr更敏感、更及时地发现AKI患者肾功能的早期损害。
Objective:
To evaluate the feasibility and clinical value of serum cystatinC in assessing glomerular filtration rate in patients with acute kidney injury.
Methods:
Fourty-six acute kidney injury (36male/10female), aged 56.2土18 years in intensive care unit were recruited in the study and blood saples were collected daily. Serum creatinine(Scr)was measured by enzymic method.Cys C was detected by ELISA(Enzyme-Linked Immunoadsorbent Assay) and glomemlar filtration rate(GFR)was estimated by Cockrofi—Gault equation.AKI was diagnosed according to ADQI(RIFLE) criteria.The correlations among SCysC, Scr and Ccr were compared by using pearson correlation analysis. Multiple regression analysis was also used to understand the influential factors to the SCysC concentration. In order to compare the diagnostic value of SCysC and Scr, the Receiver Operating Charateristic curve(ROC) was calculated and sensitivity(Sen), specificity (Spe), accuration(Acc) of SCysC and Scr were obtained and analyzed. All data were analyzed by using statistical software of SPSS13.0.
Result:
46 patients developed AKI to some degree,among which 19,11and 16patients fulfilled staging 1 ,staging 2 ,and staging 3 respectively. 71 patients without AKI served as controls.In patients with AKI,Cys C was significantly increased than that in patients who did not develop AKI(P<0.01). Serum Cys C was linearly correlated with serum creatinine(r=0.877,P<0.01),also[CysC]-1 with estimated GFR (R=0.924,P<0.01). when AKI was diagnosed according to eGFR<=60 ml/min/1.732,with the staging 1 patients serum Cys C was demonstrated a highly diagnostic value to detect AKI ,The area under the curve(AUC)of the ROC for SCysC was 0.932(95%confidence interval,0.885-1.044,p<0.01) and The area under the curve(AUC)of the ROC for SCr was 0.864(95% confidence interval,0.791-1.066,p<0.01), there are significant statistical differentce between SCysC and Scr (P<0.01).With total patients there is also signifence difference. At a cutoff of 1.832mg/L, SCysC reached a 88.7% ACC, while at a cutoff of 123.5 umol/L, Scr has a 82% ACC ,there are significant statistical differentce between SCysC and Scr (P<0.05). The sensitivities were 95.7% for CysC and 82.6% for Scr with total patients, the sensitivities were 89.5% for CysC and 57.9% for Scr with staging 1 patients, there are significant statistical differentce between SCysC and Scr. The concentration of SCysC is not affected by age, gender, body weight, hemoglobin, serum protin, glucose,total bilirubin .
Conclusions:
Cystatin C can be one of the early detection markers of AKI.Serum cystatin C is superior to serum creatinine as a predictive marker of AKI in an early stage.
探讨血清胱抑素C(SCysC)作为肾小球滤过率标志物在诊断急性肾损伤中的价值。
方法
本研究共纳入ICU患者共46例,男36例(78%),女10例(22%),年龄( 56.2土18(20-80))岁。对每例入住ICU的患者于入院当日采静脉血1.5 mL保存,测血清肌酐作为基线资料。此后,每日检测血清肌酐,并密切观察尿量变化。对按标准诊断为AKI的患者,每日清晨8:00采静脉血1.5 mL,3000转离心10分钟后留取血清并保存于-70℃冰箱,直至患者出院、转科、行RRT治疗或死亡。将肌酐值最大日的标本集中测量SCysC。采用酶法测定血清肌酐。采用酶免法(ELISA)测SCysC。肌酐清除率(Ccr)采用Cockroft--Gault公式计算,以此作为GFR的估计值。应用SPSS 13.0统计软件对数据进行统计处理。计量资料以( x土s)表示,两组均数的比较用t检验;计数资料用百分率表示,应用X2 (卡方)检验;正常人中各项指标的95%参考值范围表示为( x土2s);相关关系采用Pearson相关系数和一元线性回归分析;运用ROC分析曲线评价SCysC诊断AFR的准确性、敏感性和特异性,并且寻找SCysC的最佳截断值;应用多元线性回归分析影响SCysC浓度的因素。
结果
发生急性肾损伤的46例患者处于1,2,3期的患者分别为19,11和16例。71名健康人作为对照组。在急性肾损伤患者中SCysC较正常组明显升高(P<0.01);46例AKI患者血清SCysC与Scr成显著线性相关,相关系数(r=0.877,p<0.01); 46例AKI患者( SCysC ) -1与eGFR成显著线性相关,相关系数R=0.924,p<0.01,回归方程eGFR=-32.15+150.003(SCysC)-1或(SCysC)-1 =0.24+0.006eGFR。以患者Scr升高1.5倍作为AKI诊断标准,由ROC曲线可以看出SCysC在AKI的诊断中,曲线下面积为0.949,95%可信区间为(0.890-1.008,p<0.01)。以估算的eGFR<=60 ml/min/1.732作为AKI的诊断标准,由ROC曲线可以看出SCysC在AKI的诊断中,曲线下面积为0.970,95%可信区间为(0.964-1.014,p<0.01) ,最佳截断值为1.832 mg/l,敏感性和特异性分别为97.4%和100%。以此标准由ROC曲线可以看出Scr在AKI的诊断中,曲线下面积为0.925,95%可信区间为(0.934-1.022,p<0.01),最佳截断值为123.5μmol/l,敏感性和特异性分别为93.4%和100%,两者AUC差别有统计学意义。以估算的eGFR<=60 ml/min/1.732作为AKI的诊断标准,将第1期患者比较发现Scr在AKI的诊断中,曲线下面积为0.864,95%可信区间(0.791-1.066,p<0.01), SCysC在AKI的诊断中,曲线下面积为0.932,95%可信区间为(0.885-1.044,p<0.01),两者比较有显著差异性。以最佳截断值评价诊断效能,发现SCysC准确性(88.7%v82%)、阳性及阴性预测值较Scr高,两者总体敏感性(Sen)、特异性(Spe)无明显差异。根据求得的正常人群各项检测指标,采用参考值范围上限(SCysC为1.7 mg/l,Scr为133μmol/l )为截断值,求得两指标的灵敏度,发现所有患者CysC(95.7%)及第一期患者CysC(89.5%)的灵敏度要明显优于所有患者Scr (82.6%)及第一期患者Scr(57.9%)。SCysC浓度的变化主要受Ccr的影响,而与患者的年龄、性别、体重、血糖、血红蛋白、总胆红素、血清蛋白、血前白蛋白等因素无关。
结论
在ICU内SCysC可以作为急性肾损伤患者GFR的内源性标志物,SCysC能较Scr更敏感、更及时地发现AKI患者肾功能的早期损害。
Objective:
To evaluate the feasibility and clinical value of serum cystatinC in assessing glomerular filtration rate in patients with acute kidney injury.
Methods:
Fourty-six acute kidney injury (36male/10female), aged 56.2土18 years in intensive care unit were recruited in the study and blood saples were collected daily. Serum creatinine(Scr)was measured by enzymic method.Cys C was detected by ELISA(Enzyme-Linked Immunoadsorbent Assay) and glomemlar filtration rate(GFR)was estimated by Cockrofi—Gault equation.AKI was diagnosed according to ADQI(RIFLE) criteria.The correlations among SCysC, Scr and Ccr were compared by using pearson correlation analysis. Multiple regression analysis was also used to understand the influential factors to the SCysC concentration. In order to compare the diagnostic value of SCysC and Scr, the Receiver Operating Charateristic curve(ROC) was calculated and sensitivity(Sen), specificity (Spe), accuration(Acc) of SCysC and Scr were obtained and analyzed. All data were analyzed by using statistical software of SPSS13.0.
Result:
46 patients developed AKI to some degree,among which 19,11and 16patients fulfilled staging 1 ,staging 2 ,and staging 3 respectively. 71 patients without AKI served as controls.In patients with AKI,Cys C was significantly increased than that in patients who did not develop AKI(P<0.01). Serum Cys C was linearly correlated with serum creatinine(r=0.877,P<0.01),also[CysC]-1 with estimated GFR (R=0.924,P<0.01). when AKI was diagnosed according to eGFR<=60 ml/min/1.732,with the staging 1 patients serum Cys C was demonstrated a highly diagnostic value to detect AKI ,The area under the curve(AUC)of the ROC for SCysC was 0.932(95%confidence interval,0.885-1.044,p<0.01) and The area under the curve(AUC)of the ROC for SCr was 0.864(95% confidence interval,0.791-1.066,p<0.01), there are significant statistical differentce between SCysC and Scr (P<0.01).With total patients there is also signifence difference. At a cutoff of 1.832mg/L, SCysC reached a 88.7% ACC, while at a cutoff of 123.5 umol/L, Scr has a 82% ACC ,there are significant statistical differentce between SCysC and Scr (P<0.05). The sensitivities were 95.7% for CysC and 82.6% for Scr with total patients, the sensitivities were 89.5% for CysC and 57.9% for Scr with staging 1 patients, there are significant statistical differentce between SCysC and Scr. The concentration of SCysC is not affected by age, gender, body weight, hemoglobin, serum protin, glucose,total bilirubin .
Conclusions:
Cystatin C can be one of the early detection markers of AKI.Serum cystatin C is superior to serum creatinine as a predictive marker of AKI in an early stage.
引文
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27 Molls R,Sawansky V,Liu MC,et a1.Keratinocyte—derived chemokines is an early biomarker of ischemia acute kidney injury.Am J Physiol Renal Physiol,2005;Dec 20.
28 Lau LF,Lam SC:The CCN family of angiogenic regulators:the integrin connection.Exp Cell Res 1999,248:44-57.
29 Brigstock DR:Theconnective tissue growth factor/cysteine-rich 61/nephroblastoma over expressed(CCN)family.Endocr Rev 1999,20:189-206.
30 Latinkic BV,Mo FE,Greenspan JA,et al.:Promoter function of the angiogenic Inducer Cyr61 gene intransgenic mice:tissue specificity,inducibility during Wound healing,and role of the serum response element.Endocrinology 2001,142:2549-2557.
31Chen CC,Chen N,Lau LF:The angiogenic factors Cyr61 and connective Tissue growth factor induce adhesive signaling in primary human skin fibroblasts.J Biol Chem 2001,276:10443-10452.
32 ChenCC,MoFE,LauLF:The angiogenic factor Cyr61 activates a genetic Program for wound healing in human skin fibroblasts.J Biol Chem 2001,276:47329-47337.
33 Muramatsu Y,Tsujie M,Kohda Y,et al.:Early detection of cysteine rich protein
61(CYR61,CCN1)in urine following renal ischemic reperfusion injury.KidNey Int2002,62:1601-1610.
34 Kwon o,Molitoris BA,Pescovitz M,et al.:Urinary actin,inter leukin-6,and interleukin-8may predict sustained ARF after ischemic injury in renal allografts.Am J Kidney Dis 2003,41:1074-1087.
35 Sundberg AG,Appelkvist EL,BackmanL,et al.:Urinary pi-class glutathione Transferase as an indicator of tubular damage in the human kidney.Nephron 1994,67:308-316.
36 Westhuyzen J,Endre ZH,Reece G,et al.:Measurement of tubular enzymuria Facilitates early detection of acute renal impairment in the intensive care unit Nephrol Dial Transplant2003,18:543-551.
37 Kwon O,Molitofis BA,Pescovitz M,et a1.Urinary actin,interleukin -6,and interleukin-8 may predict susta/ned ARF after ischemic injury in renal allografts.J Kidney Dis,2003,41:1074-108.
38 BonventreJV:The kidney proteome:a hint of things to come .Kidney Int 2002,62:1470-1471.
[1] Hoste EA,Clermont G,Kersten A,et a1.RIFLE criteria for acute kidneyinjury are associated with hospital mortality in critically ill patients:a cohort analysis.Crit Care,2006,10(3):R73.
[2] Barrett AJ. The cystatins: small protein inhibitors of cysteine proteinases.Prog Clin Biol Res 1985; 180:105-116. Bibliographic Links Library Holdings.
[3] RandersE,KrueS,ErlandsenEJ,et a1.Reference interval for serum cystatin C in children[J].C1in Chem,1999,45:1856.
[4] AbrahamsonM ,Olafsson1 ,Palsdottir A ,et al. Structure and Expression of the human cystatinC gene. Biochem J,1990,268:28 7-294.
[5]Grubb A. Diagnostic value of analysis of cystatin C and protein HC in Biological fluids. Clin Nephrol,1992,38 :S20-s27.
[6]Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 2004; 65:1416-1421. Full Text Bibliographic Links Library Holdings
[7] Manetti L, Pardini E, Genovesi M, et al. Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 2005;28:346-349. Bibliographic Links Library Holdings
[8] Risch L, Herklotz R, Blumberg A, et al. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001;47:2055-2059. Bibliographic Links Library Holdings
[9] Wasen E, Isoaho R, Mattila K, et al. Serum cystatin C in the aged: relationships with health status. Am J Kidney Dis 2003; 42:36-43.
[10] Dhamidharka VR,Kwon C, Stevens G,Serum systatinC is superior to serum creatinine as a marker of kindney function:a metalysis.Am J kidney Dis 2002;40:221-226.
[11] Uzun H,Ozmen Keles M, Ataman R,et al.Serum systatinC level as a potentially good marker for impaired kindey function.Clin Biochem.2005 Sep ;38(9):792-8
[12] H0JS R,Bevc S,Ekart R,et al.Serum systatin C as an endogenous marker of renal function in patients with mild to moderate impairment of Kinney Funtion.Nephrol Dial Transplant.2006 mar8
[13] Ascic-buturovic B,Cavaljuga S. Serum systatinC as a marker of early renal failure in diabetes type 2 patients.Bosn J Basic Med Sci.2005 Nov;5(4):68-71
[14] Bicik Z,Bahcebasi T,Kulaksizoglu S,et al. The efficacy of systatinC assay in the prediction of glomerular filtration rate.Is it more reliable marker for renal failure? Clin Chem Lab Med.2005;43(8):855-61
[15] Christensson AG,Grubb AO,Nilsson JA,et al.Serum cycstain C advantageous compared with serum creatinine in the detection of mind but not severe diabetic nephropathy.J Intern Med.2004 Dec;256(6):510-8.
[16] Herget—Rosenthal S,Marggrat G,Husing J,et a1.Early detection of acute renal failure by Serum cystatin C.Kidney Int。2004,sep:66(3):lll5-l122.
[17]彭先强,史伟,叶智明,等.检测血清胱抑素c诊断急性肾衰的研究.新医学,2005,36(10):570-571.
[18] Ahlstrom A,Tallgren M,Peltonen S,et a1.Evaluation and predictive power of serum cystatin C in acute renal failure.Clin Nephro1.2004, 62(5):344-350.
[19] Le Bricon.on T,Thervet E,Frossart M,et a1.Plasma cystatin C is superior to creatinine clearance for estimation of GFR three months after kidney transplantation[J].Clin Chem,2000,46:1206.
[20] White C, Akbari A, Hussain N, et al. Estimating glomerular filtration rate in kidneytransplantation: a comparison between serum creatinine and cystatin C-based methods. J Am Soc Nephrol 2005; 16:3763-3770.
[21] Caring for Australasians with Renal Impairment (CARI). Guidelines. Use of cystatin C measurement in evaluating kidney function. [website] 2005; http://www.cari.org.au/ckd_evaluation_function_list.php. [Accessed 12 June 2006].
[22] Burkhardt H, Bojarsky G, Gladisch R. Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced glomerular filtration rate in the elderly. Clin Chem Lab Med 2002; 40:1135-1138.
[23] Van den Noortgate NJ, Janssens WH, Afschrift MB, et al. Renal function in the oldest-old on an acute geriatric ward. Int Urol Nephrol 2001; 32:531-537.
[24] Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J Kidney Dis 2001; 37:79-83.
[25] O'Riordan SE, Webb MC, Stowe HJ, et al. Cystatin C improves the detection of mild renal dysfunction in older patients. Ann Clin Biochem 2003; 40:648-655.
[26] Caregaro L, Menon F, Angeli P, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994; 154:201-205.
[27] Takabatake T, Ohta H, Ishida Y, et al. Low serum creatinine levels in severe hepatic disease. Arch Intern Med 1988; 148:1313-1315.
[28] Perkins BA, Nelson RG, Ostrander BE, et al. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J Am Soc Nephrol 2005; 16:1404-1412.
[2] Molitoris, Bruce A *; Levin, Adeera; Warnock, David G; Joannidis, Michael; Mehta, Ravindra L; Kellum, John A; Ronco, Claudio; Shah, Sudhir V; on behalf of the Acute Kidney Injury Network working group Improving outcomes of acute kidney injury: report of an initiative. Nature Clinical Practice Nephrology. 2007,3(8):439-442.
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[15] Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol 1992; 38(Suppl 1):S20-S27.
[16] Tenstad O, Roald AB, Grubb A, et al. Renal handling of radiolabelled human cystatin C in the rat. Scand J Clin Lab Invest 1996; 56:409-414.
[17] Finney H, Newman DJ, Thakkar H, et al. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.Arch Dis Child 2000; 82:71-75.
[18] Norlund L, Fex G, Lanke J, et al. Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta 2-microglobulin/ cystatin C-ratio. Scand J Clin Lab Invest 1997; 57:463-470.
[19] Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 2004; 65:1416-1421.
[20] Manetti L, Pardini E, Genovesi M, et al. Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 2005;28:346-349.
[21] Risch L, Herklotz R, Blumberg A, et al. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001; 2055-2059.
[22] Wasen E, Isoaho R, Mattila K, et al. Serum cystatin C in the aged: relationships with health status. Am J Kidney Dis 2003; 42:36-43.
[23] Dhamidharka VR,Kwon C, Stevens G,Serum systatinC is superior to serum creatinine as a marker of kindney function:a metalysis.Am J kidney Dis 2002;40:221-226.
[24] Uzun H,Ozmen Keles M, Ataman R,et al.Serum systatinC level as a potentially good marker for impaired kindey function.Clin Biochem.2005 Sep ;38(9):792-8
[25] H0JS R,Bevc S,Ekart R,et al.Serum systatin C as an endogenous marker of renal function in patients with mild to moderate impairment of Kinney Funtion.Nephrol Dial Transplant.2006 mar 8.
[26] Ascic-buturovic B,Cavaljuga S. Serum systatinC as a marker of early renal failure in diabetes type 2 patients.Bosn J Basic Med Sci.2005 Nov;5(4):68-71.
[27] Bicik Z,Bahcebasi T,Kulaksizoglu S,et al. The efficacy of systatinC assay in the prediction of glomerular filtration rate.Is it more reliable marker for renal failure? Clin Chem Lab Med.2005;43(8):855-61.
[28] Christensson AG,Grubb AO,Nilsson JA,et al.Serum cycstain C advantageous compared with serum creatinine in the detection of mind but not severe diabetic nephropathy.J Intern Med.2004 Dec;256(6):510-8.
[29] Hoste EA,Clermont G,Kersten A,et a1.RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients:a cohort analysis.Crit Care,2006,10(3):R73.
[30] Herget-Rosenthal S, Marggraf G, Husing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004; 66:1115-1122.
[31]梁馨苓,史伟,彭炎强,等、血清半胱氨酸蛋白酶抑制剂C在急性肾衰早期诊断中的价值[J].中华肾脏病杂志,2006,22(2):7679.
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9 Nortier JL,Deschodt-Lanckman MM,Simon S,etal.:Proximal tubular injury in Chinese herbs nephropathy:monitoring by neutral endopeptidase enzymuria. Kidney Int 1997,51:288-293.
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13 IchimuraT,BonventreJV,BaillyV,et al.:Kidney injury molecule-1(KIM-1),a Putative epithelial cell adhesion molecule containing a novel immunoglobulin domain,is up-regulated in renal cells after injury.J Biol Chem 1998,273:4135-4142.
14 Vaidya VS,Ramirez V,Ichimura T,et a1.Urinary kidney injury Molecule-l:a sensitive quantitative biomarker for early detection of kidney tubular injury.Am J Physiol Renal Physiol,2OO6,290(2): F5I7-F529.
15 du CheyronD,DaubinC,Poggioli J,et al.:Urinary measurement of Na+/H+ Exchanger isoform3(NHE3) protein as new marker of tubule injury in critically ill patients with ARF.Am J Kidney Dis 2003,42:497-506.
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17 Vyacheslav Y,Melnikov J,Tevfik E,et a1.Impaired IL-l8 processing protects caspase-l:deficient mice from ischemia acute renal failure.Clin Invest,2001,107:l145-l152.
18 Parikh CR,Jani A,Melnikovy,et a1.Urinary interleukin-l8 is a marker of human acute tubular necrosis. Am J Kidney Dis,2004:Mar 43(3)405-414.
19 KwonO,MolitorisBA,PescovitzM,et al.:Urinary actin,interleukin-6,and interleukin-8 may predict sustained ARF after ischemic injury in renal allografts.Am J Kidney Dis 2003,41:1074-1087.
20 Di Paolo S,Gesualdo L,Stallone G,et al.:Renal expression and urinary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients.Nephrol Dial Transplant 1997,12:2687-2693.
21 Kwon O,Molitofis BA,Pescovitz M,et a1.Urinary actin,interleukin-6,and interleukin-8 may predict sustained ARF after ischemic injury in renal allografts.J Kidney Dis,2003,41:1074-1087.
22 Mishra J,Ma Q,Prada A,et a1.Identification of neutrophil gelatinase-associated lipecalin as a novel early urinary biomarker for ischemia renal injury.J Am Soc Nephrol,2003,14:2534-2543.
23 Mishra J , Dent C , Tarabishi R , et a1 . Neutrophil gelatinase—asscciated lipoealin(NGAL)as a biomarker for acute renal injury after cardiac surgery.Lancet,2005,365:1231-1238.
24 Herget—Rosenthal S,Marggrat G,Husing J,et a1.Early detection of acute renal failure by Serum cystatin C.Kidney Int。2004,sep:66(3):lll5-l122
25彭先强,史伟,叶智明,等.检测血清胱抑素c诊断急性肾衰的研究.新医学,2005,36(10):570-571.
25Ahlstrom A,Tallgren M,Peltonen S,et a1.Evaluation and predictive power of serum cystatin C in acute renal failure.Clin Nephro1.2004, 62(5):344-350.
26 Safristein R,Megyesi J,Saggi SJ,et a1.Expression of cytokine-like gene.JE and KC is increased during renal ischemia.Am J Physiol 199l:26l:F1095一F1101.
27 Molls R,Sawansky V,Liu MC,et a1.Keratinocyte—derived chemokines is an early biomarker of ischemia acute kidney injury.Am J Physiol Renal Physiol,2005;Dec 20.
28 Lau LF,Lam SC:The CCN family of angiogenic regulators:the integrin connection.Exp Cell Res 1999,248:44-57.
29 Brigstock DR:Theconnective tissue growth factor/cysteine-rich 61/nephroblastoma over expressed(CCN)family.Endocr Rev 1999,20:189-206.
30 Latinkic BV,Mo FE,Greenspan JA,et al.:Promoter function of the angiogenic Inducer Cyr61 gene intransgenic mice:tissue specificity,inducibility during Wound healing,and role of the serum response element.Endocrinology 2001,142:2549-2557.
31Chen CC,Chen N,Lau LF:The angiogenic factors Cyr61 and connective Tissue growth factor induce adhesive signaling in primary human skin fibroblasts.J Biol Chem 2001,276:10443-10452.
32 ChenCC,MoFE,LauLF:The angiogenic factor Cyr61 activates a genetic Program for wound healing in human skin fibroblasts.J Biol Chem 2001,276:47329-47337.
33 Muramatsu Y,Tsujie M,Kohda Y,et al.:Early detection of cysteine rich protein
61(CYR61,CCN1)in urine following renal ischemic reperfusion injury.KidNey Int2002,62:1601-1610.
34 Kwon o,Molitoris BA,Pescovitz M,et al.:Urinary actin,inter leukin-6,and interleukin-8may predict sustained ARF after ischemic injury in renal allografts.Am J Kidney Dis 2003,41:1074-1087.
35 Sundberg AG,Appelkvist EL,BackmanL,et al.:Urinary pi-class glutathione Transferase as an indicator of tubular damage in the human kidney.Nephron 1994,67:308-316.
36 Westhuyzen J,Endre ZH,Reece G,et al.:Measurement of tubular enzymuria Facilitates early detection of acute renal impairment in the intensive care unit Nephrol Dial Transplant2003,18:543-551.
37 Kwon O,Molitofis BA,Pescovitz M,et a1.Urinary actin,interleukin -6,and interleukin-8 may predict susta/ned ARF after ischemic injury in renal allografts.J Kidney Dis,2003,41:1074-108.
38 BonventreJV:The kidney proteome:a hint of things to come .Kidney Int 2002,62:1470-1471.
[1] Hoste EA,Clermont G,Kersten A,et a1.RIFLE criteria for acute kidneyinjury are associated with hospital mortality in critically ill patients:a cohort analysis.Crit Care,2006,10(3):R73.
[2] Barrett AJ. The cystatins: small protein inhibitors of cysteine proteinases.Prog Clin Biol Res 1985; 180:105-116. Bibliographic Links Library Holdings.
[3] RandersE,KrueS,ErlandsenEJ,et a1.Reference interval for serum cystatin C in children[J].C1in Chem,1999,45:1856.
[4] AbrahamsonM ,Olafsson1 ,Palsdottir A ,et al. Structure and Expression of the human cystatinC gene. Biochem J,1990,268:28 7-294.
[5]Grubb A. Diagnostic value of analysis of cystatin C and protein HC in Biological fluids. Clin Nephrol,1992,38 :S20-s27.
[6]Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 2004; 65:1416-1421. Full Text Bibliographic Links Library Holdings
[7] Manetti L, Pardini E, Genovesi M, et al. Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 2005;28:346-349. Bibliographic Links Library Holdings
[8] Risch L, Herklotz R, Blumberg A, et al. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001;47:2055-2059. Bibliographic Links Library Holdings
[9] Wasen E, Isoaho R, Mattila K, et al. Serum cystatin C in the aged: relationships with health status. Am J Kidney Dis 2003; 42:36-43.
[10] Dhamidharka VR,Kwon C, Stevens G,Serum systatinC is superior to serum creatinine as a marker of kindney function:a metalysis.Am J kidney Dis 2002;40:221-226.
[11] Uzun H,Ozmen Keles M, Ataman R,et al.Serum systatinC level as a potentially good marker for impaired kindey function.Clin Biochem.2005 Sep ;38(9):792-8
[12] H0JS R,Bevc S,Ekart R,et al.Serum systatin C as an endogenous marker of renal function in patients with mild to moderate impairment of Kinney Funtion.Nephrol Dial Transplant.2006 mar8
[13] Ascic-buturovic B,Cavaljuga S. Serum systatinC as a marker of early renal failure in diabetes type 2 patients.Bosn J Basic Med Sci.2005 Nov;5(4):68-71
[14] Bicik Z,Bahcebasi T,Kulaksizoglu S,et al. The efficacy of systatinC assay in the prediction of glomerular filtration rate.Is it more reliable marker for renal failure? Clin Chem Lab Med.2005;43(8):855-61
[15] Christensson AG,Grubb AO,Nilsson JA,et al.Serum cycstain C advantageous compared with serum creatinine in the detection of mind but not severe diabetic nephropathy.J Intern Med.2004 Dec;256(6):510-8.
[16] Herget—Rosenthal S,Marggrat G,Husing J,et a1.Early detection of acute renal failure by Serum cystatin C.Kidney Int。2004,sep:66(3):lll5-l122.
[17]彭先强,史伟,叶智明,等.检测血清胱抑素c诊断急性肾衰的研究.新医学,2005,36(10):570-571.
[18] Ahlstrom A,Tallgren M,Peltonen S,et a1.Evaluation and predictive power of serum cystatin C in acute renal failure.Clin Nephro1.2004, 62(5):344-350.
[19] Le Bricon.on T,Thervet E,Frossart M,et a1.Plasma cystatin C is superior to creatinine clearance for estimation of GFR three months after kidney transplantation[J].Clin Chem,2000,46:1206.
[20] White C, Akbari A, Hussain N, et al. Estimating glomerular filtration rate in kidneytransplantation: a comparison between serum creatinine and cystatin C-based methods. J Am Soc Nephrol 2005; 16:3763-3770.
[21] Caring for Australasians with Renal Impairment (CARI). Guidelines. Use of cystatin C measurement in evaluating kidney function. [website] 2005; http://www.cari.org.au/ckd_evaluation_function_list.php. [Accessed 12 June 2006].
[22] Burkhardt H, Bojarsky G, Gladisch R. Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced glomerular filtration rate in the elderly. Clin Chem Lab Med 2002; 40:1135-1138.
[23] Van den Noortgate NJ, Janssens WH, Afschrift MB, et al. Renal function in the oldest-old on an acute geriatric ward. Int Urol Nephrol 2001; 32:531-537.
[24] Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J Kidney Dis 2001; 37:79-83.
[25] O'Riordan SE, Webb MC, Stowe HJ, et al. Cystatin C improves the detection of mild renal dysfunction in older patients. Ann Clin Biochem 2003; 40:648-655.
[26] Caregaro L, Menon F, Angeli P, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994; 154:201-205.
[27] Takabatake T, Ohta H, Ishida Y, et al. Low serum creatinine levels in severe hepatic disease. Arch Intern Med 1988; 148:1313-1315.
[28] Perkins BA, Nelson RG, Ostrander BE, et al. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J Am Soc Nephrol 2005; 16:1404-1412.