Cystatin C、Scr及尿微量蛋白在慢性肾脏病患者GFR评估中的比较研究
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摘要
目的探讨血清半胱氨酸蛋白酶抑制剂C (Cystatin C )、血清肌酐(Scr)及尿微量蛋白(α1-MG、ALB、TRF)在评价慢性肾脏病患者肾功能损害中的比较及血清CysC浓度判定在肾小球滤过功能中的临床价值。方法收集自2008年1月至2008年11月本院住院的慢性肾脏病患者62例,采用酶联免疫吸附实验(ELISA)检测每例患者的血清半胱氨酸蛋白酶抑制剂C的浓度,同时记录每例患者的血清肌酐及尿微量蛋白(α1-MG、ALB、TRF)的浓度。依据Cockcroft-Gault方程及本院实验室所测内生肌酐清除率(Ccr)两者的均值为实际Ccr。以MDRD方程计算出的近似肾小球滤过率(eGFR)为评价标准,来比较Cystatin C,、Scr、Ccr、尿α1-MG、ALB、TRF与eGFR的相关性。采用受试者工作特征曲线下面积(AUCROC)和灵敏度来评价Cystatin C的可靠性。结果患者血清Cystatin C, Scr, Ccr与eGFR均呈显著相关,相关系数分别为-0.940,-0.931,0.935(P均<0.01)。尿α1-MG、ALB、TRF与eGFR的相关程度较低,相关系数分别为-0.554,-0.484,-0.237。各指标以Cystatin C与eGFR的相关程度最密切。CysC、Scr、α1-MG、ALB、TRF的AUCROC分别为0.985,0.924,0.732,0.682,0.564,以CysC的AUCROC最大,且Cystatin C与Scr的AUCROC之间比较具有统计学意义(P<0.05),Cystatin C与α1-MG的AUCROC之间比较具有统计学意义(P<0.01),灵敏度也以血清Cystatin C较Scr、α1-MG、ALB、TRF为佳(灵敏度分别为96.8%、91.9%、87.1%,80.6%,79.0%)。结论与血清Scr、尿α1-MG、ALB、TRF相比,血清Cystatin C是一个更为准确、灵敏的反映肾小球滤过功能的指标,对较早期反映各种慢性肾脏病患者肾小球滤过功能的损害具有重要价值。
Objective: To evaluate the applicability of serum cystatin C ,serum creatinine and urine microprotein as endogenous marker for detection of renal disfunction in patients with chronic kidney disease. Methods:Serum samples were obtained from 62 cases who were got with chronic kidney disease, collected from January in 2008 to November in 2008 among our own hospitalized patient. Serum cystatin C concentration was determined by enzyme-linked immunosorbent assay(ELISA),and we record every illness’s Serum creatinine(Scr) and urine microprotein (α1-MG、ALB,TRF),and we measured Creatinine clearance rate(Ccr) accord to Cockcroft-Gault equations and our native hospital analysis ,and then we mean the two numerical value as the last numerical values. At the same time, we evaluate the estimated glomerular filtration rate( eGFR) accord to equations MDRD,then we serve eGFR as evaluation criterion,to compare the relation among CysC,Scr,Ccr,α1-MG,ALB,TRF and eGFR. The correlation between eGFR and above parameters were compared,and the areas which under the Receiver Operating Chacteristic curve(AUCROC), and the sensitivity ,they were all used for revaluating the reliability of cystatinC。Results: We found significant correlation between eGFR and cystatin C, Scr, Ccr,r is -0.940,-0.931,-0.935 respectively (p<0.01)。α1-MG,ALB and TRF have a low relationship between eGFR, r is -0.554,-0.484,-0.237 respectively。So the relationship between eGFR and cystatin C was the most strongest。The AUCROC for cystatinC ,Scr ,α1-MG,ALB,TRF are 0 .985, 0.924,0.732,0.682,0.564 respectively, there was significant statistical difference between cystatin C and Scr (P<0.05),and there was also significant statistical difference between cystatin C andα1-MG (P<0.01)。To refer to sensitivity ,the serum cystatin C was the best among the above five parameters,the sensitivity are 96.8%, 91.9%,87.1%,80.6%,79.0%respectively。Conclusion: serum cystatin C determination is an accurate and ready-witted parameter of GFR。It can be a better endogenous marker for detection of early renal disfunction in patients who were with chronic kidney disease than serum creatinine ,urineα1-MG,ALB and TRF。
Objective: To evaluate the applicability of serum cystatin C ,serum creatinine and urine microprotein as endogenous marker for detection of renal disfunction in patients with chronic kidney disease. Methods:Serum samples were obtained from 62 cases who were got with chronic kidney disease, collected from January in 2008 to November in 2008 among our own hospitalized patient. Serum cystatin C concentration was determined by enzyme-linked immunosorbent assay(ELISA),and we record every illness’s Serum creatinine(Scr) and urine microprotein (α1-MG、ALB,TRF),and we measured Creatinine clearance rate(Ccr) accord to Cockcroft-Gault equations and our native hospital analysis ,and then we mean the two numerical value as the last numerical values. At the same time, we evaluate the estimated glomerular filtration rate( eGFR) accord to equations MDRD,then we serve eGFR as evaluation criterion,to compare the relation among CysC,Scr,Ccr,α1-MG,ALB,TRF and eGFR. The correlation between eGFR and above parameters were compared,and the areas which under the Receiver Operating Chacteristic curve(AUCROC), and the sensitivity ,they were all used for revaluating the reliability of cystatinC。Results: We found significant correlation between eGFR and cystatin C, Scr, Ccr,r is -0.940,-0.931,-0.935 respectively (p<0.01)。α1-MG,ALB and TRF have a low relationship between eGFR, r is -0.554,-0.484,-0.237 respectively。So the relationship between eGFR and cystatin C was the most strongest。The AUCROC for cystatinC ,Scr ,α1-MG,ALB,TRF are 0 .985, 0.924,0.732,0.682,0.564 respectively, there was significant statistical difference between cystatin C and Scr (P<0.05),and there was also significant statistical difference between cystatin C andα1-MG (P<0.01)。To refer to sensitivity ,the serum cystatin C was the best among the above five parameters,the sensitivity are 96.8%, 91.9%,87.1%,80.6%,79.0%respectively。Conclusion: serum cystatin C determination is an accurate and ready-witted parameter of GFR。It can be a better endogenous marker for detection of early renal disfunction in patients who were with chronic kidney disease than serum creatinine ,urineα1-MG,ALB and TRF。
引文
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[2].Smith HW. The kidney structure and function in health and disease. New York:Oxford University Press,1951:63-66.
[3].YoungDS. Efects of Drugs on Clinical Laboratory Tests. American Association of Cinical hemistry Press.Washington,D C,1995.
[4].Norden G, Bjorck S, Granerus G ,et al. Estimation of renal function in diabetic nephropathy-comparison of five methods. Nephron.1987;47(1):36-42.
[5]. Simonsen O ,Grubb A ,Thysll H. The blood serum concentration of cystatin C (γ-trace) as a measure of the glomerular filtration rate[J ] . Scand J Clin Invest , 1985 ,45 (2) :97-102.
[6]. Price CP, Finney H, Developments in the assessment of glomerular filtration rate. Clin Chim Acta 2000;297:55-66
[7]. Tain S,Kusano E,Ohara T,et a1.Cysctain C measurement and its pratical use in patients with various renal disease[J].Clin Nephrol 1997,48(1):104-108.
[8].李玉林,徐国宾,朱立华.Cystatin C与肌酐在评价肾小球滤过功能中的比较研究[J].中国实验诊断学杂志,2001,5(4):154-156.
[9] Le Bricon T,Thervet E,Froissart M,et a1.Plasma cystatin C:a better marker of glomerular filtration rate than creatinine in kidney transplantation[J].Clinical Biol Chem,2000,33(1):232.
[10].施岚,吴亚君,崔世雄.CysC、Cr及β2-M比较分析肾功能损害[J].放射免疫学杂志,2002,15(5):306-307.
[11].黄萍,李国贤.测定血清胱抑素-C在评估肾脏功能中的意义.临床肾脏病杂志,2003,3(2):61-63.
[12].沈清,甘华.血清CystatinC对肾小球滤过功能的探讨.重庆医学,2002,31(6):458-450.
[13]. Abrahamson M,Olafsson I,Palsdottir A,et al.Structure and expression of the human cystatinC gene.Biochem J 1990;268:287-94.
[14].Tenstad O,Ronald AB,Grubb A, et al.Renal handling of radiolabelled human CystatinC in the rat.Scand J Clin Lab Invest.1996;56(5):409-14.
[15].Laterza OF, Price CP, Scott MG. CystatinC: an improved estimator of glomerular filtration rate? Clin Chem,2002,48:699-707.
[16]. Filler G ,Priem F,Vollmer I,et a1.Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate.Pediatr Nephrol,1999,13(6):501-505.
[17].罗长青,王玉梅,邓安国,等.测定血清Cystatin C浓度判断肾小球滤过率的临床意义.临床内科杂志,2003,20(3):154
[18]. Nina Cimerman, Pima mesko brguljan, Marta Krasovec et al. Twenty-Four hour variations of cystatin C and total cysteine proteinase inhibitory activity in sera from healthy subjects [J]. Clin Chim Acta, 2000,291(1):89-95.
[19].Nina Cimerman, Pima mesko brugljan, Marta Krasovec et al. Serum cystatin C, an inhibitory of cysteinases,is elevated in asthmatic patients [J]. Clin Chim Acta,2000(300):83-95.
[20].Dharnidharka VR, Kwonc, Stevens G, Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 2002; 40:221-226.
[21].Uzun H, Ozmen Keles M, Ataman K, et al. Serum cystatin C level as a potentionally good marker for impaired kidney function .Clin Biochem. 2005 Sep; 38(9):792-8.
[22].Bicik Z, Bahcebasi T, Knlaksizoglu S,et al. The efficiency of cystatin C assay in the prediction of glomerular filtration rate:Is it a more reliable marker for renal failure? Clin Chem Lab Med.2005;43(8):855-61.
[23].Oddozec, Moranges, Portugal H, et al. Cystatin C is not more sensitive for detecting early renal impairment in patients with diabetes. Am J kidney Dis.2001 Aug;38(2):310-6.
[24].Chantrel F, AginA, offner M, et al. Comparison of Cystatin C versus creatinine for detection of mild renal failure. Clin Nephrol.2000 Nov;54(5):374-81.
[25].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(4):1416-1421.
[26].Donadio C, Lucchesi A, Ardini M, et al. Cystatin C,β2-microglobbulin and retinolbinding protein as indicators of glomerular filtration rate :comparison with plasma creatinine. J pharm Biomed Anal 2001;24(3):835-842
[27].Levey AS, Bosch JP, Levis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new predication equation[J]. Ann Intern Med, 1999,130(6):461-470
[28].Lance D. Dworkin. Serum cystatin C as a marker of glomerular filtration rate[J]. Current Opinion in Nephrology and Hpertension,2001,10:551-553.
[29].姜搅.肾功能检查见:董德长,主编.实用肾脏病学.第一版上海:上海科学技术出版社,1999.12.1215-1216
[30].K/DOQI clinical practice guidelines for chronic kidney disease:evaluation classification,and stratification.Kidney Disease Outcome Quality Initiative[J].Am J Kidney Dis,2002,39(Suppl 2):S1-S246.
[31].Risch L, Herklotz R, Blumberg A,et al. Effects of glucocoriticoid immune suppression on serum cystatin C concentrations in renal transplant patients. Clin chim 2001; 47:2055-2059.
[32].Fricker M, W, Wiesli P,Brandle M,et al. Impact of thyroid dysfunction on serum cystatin C. Kidney Int 2003; 63:1944-1947.
[33].徐国宾,李志艳.应重视实验室检查在慢性肾病早期诊断中的应用[J].中华检验医学杂志,2006,29(11):961-964.
[34].David JN,Hansa T,Robert GD,et a1.Serum CystatinC measured by automated immunoassay:a more sensitive marker of changes in GFR than serum creatinine [J].Kidney Internationa1.1995.47(1):312.
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