半胱氨酸蛋白酶抑制剂C在肾移植术后移植物功能损伤早期检测中的应用价值探讨
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摘要
目的：
1．找到一种用于肾移植后肾功能检测的新指标，初步应用于肾移植后移植物功能的检测，并探讨其水平与移植肾功能(肾小球滤过率)的关系。
2．通过对术后半胱氨酸蛋白酶抑制剂C、血清肌酐(sCr)、尿素氮(BUN)各项指标的比较，探讨半胱氨酸蛋白酶抑制剂C作为早期肾功能损伤评估指标的应用价值。
方法：
采用回顾性分析方法，70例肾移植患者术后一月内动态监测血清肌酐、半胱氨酸蛋白酶抑制剂C，并用Modification of Diet in Renal Disease equation(MDRD公式)计算内生肌酐清除率。研究对象分为肾功能正常组(A组，31例，GFR≥90ml／min／1．73m~2)、轻度受损组(60≤GFR<90ml／min／m~2)组和肾功能中重度受损组(D组，4例，GFR<60ml／min／m~2)．依据血清肌酐正常与否，肾功能轻度受损组又分为肌酐正常组(B组，23例，Scr≤133μmol／L)和肌酐异常组(C组，12例，Scr>133μmol／L)。并与正常对照组(60例)相比较。分别绘制各组Cys C和SCr与CCr关系的散点图，并求出相关系数r。采用免疫增强散射比浊法测定半胱氨酸蛋白酶抑制剂C的水平，以流式细胞术连续检测CD4／CD8比值，ELISA检测免疫抑制剂药物浓度，评估机体的免疫状态。血生化仪测定血肌酐、尿素氮。
结果：
1．健康正常对照人群半胱氨酸蛋白酶抑制剂C的浓度是(0．72±0．13)mg／L。血清肌酐浓度为(50．48±15．20)μmol／L。
2．各组移植前半胱氨酸蛋白酶抑制剂C、血清肌酐、和尿素氮水平无显著差异(P>0．05)。
3 A组半胱氨酸蛋白酶抑制剂C浓度为(0．96±0．10)mg／L．B组半胱氨酸蛋白酶抑制剂C浓度为(1．37±0．14)mg／L．与A组对照比较有统计学差异(P<0．05)。
4．A组血清肌酐浓度为(90．51±9．86)μmol／L．B组血清肌酐浓度为(105．27±13．76)μmol／L．与A组对照比较无统计学差异(P>0．05)
5．GFR在A、B、C组与SCr、Cys C均呈直线相关，其中r分别为-0．7272和-0．7439，-0．7072和-0．7543，-0．7430和-0．7669。
结论：
Cys C浓度在肾移植术后肾功能损伤早期检测中具有重要价值。在肌酐虽然正常但CCr已经降低的患者中，其浓度已有显著变化，Cys C与肌酐清除率在肾功能正常和轻度受损患者中均呈直线相关性，其相关系数与血肌酐相比，甚至优于血清肌酐。Cystatin C单项诊断肾功能损伤时变化更明显，性能优于其他指标。由于其不受体内分解代谢，饮食等因素干扰，所以可以应用于临床，作为肾移植术后肾功能检测的常规检测指标。外周血Cystatin C检测作为一个评估移植肾功能的指标具有无创性，结果显示Cystatin C具有很高的临床应用价值，可以简便、省时、准确的应用于大量的移植患者术后移植物功能的监测。
Objects
1 To find a new index to detect the renal function after renal transplantation. This index was used in detecting the graft function. Meanwhile we rearch the relationship between Cystatin C and GFR (glomerular filtration rate).
2Through compared with Scr and BUN, to show the vulue of Cystatin C as an index in detecting the graft function after renal transplantation. And the value of cystatin C (Cys C) in the early detection of the graft function damagement after renal transplantation and providing evidence for the further diagnosis and treatment.
Methodology
At the twelfth day post-transplantation, monitored the concentration ofCys C, blood urea nitrogen (BUN) , Serum creatinine (SCr) and the glomerular filtration rate (GFR). GFR was determined by the Modification of Diet in Renal Disease equation (MDRD equation). According to the value of GFR post-transplantation, 70 cases of renal transplant patients were divided into group A (31 cases, with the normal renal function, GFR=90ml/min/1.73m~2), group B (Scr=133μmol/L, 60=GFR<90ml/min/1.73m~2, 27 cases), group C (Scr > 133μmol/L, 60=GFR<90ml/min/1.73m~2,12 cases) and group D (GFR < 60ml/min/1.73m~2, 4 cases). Meanwhile, the normal control group (n = 60) was compared. Analysis the linear correlation between Cys C, Scr and GFR through the scatterplots in each groups, and calculated the correlation coefficient(r). Determination of Cys C was performed using the Behring BN II Pro Spec analyzer. Meanwhile, used the automatic biochemistry analyzer and correlated kits to analysis the serum creatinine concentration.
Results
1. Cys C concentration in normal control group was 0.72±0.13 mg/L. Scr concentration was 50.48±15.20μmol/L.
2. The concentration of Scr, Cystatin C and BUN had no conspicuous statistically significance (P>0.05), compared with the normal control pre-transplantation.
3. Cys C concentration in group B (27 cases) were (1.37±0.14), the difference has conspicuous statistically significance (P<0.01), compared with that of group A (0.96±0.10) mg/L.
4.Scr concentration in group B (27 cases) were (105.26±13.76)μmol/L, the difference has no statistically significance (P>0.05), compared with that of group A (90.51±9.86)μmol/L.
5.Through the scatterplot, SCr and Cys C showed similar linear correlation with GFR in group A, B and C. The correlation coefficient (r) of each group was -0.7272 and -0.7439, -0.7072 and -0.7543, -0.7430 and -0.7669.
Conclusion
Cys C concentration was not influenced by diet, infection. Compared with the Scr, Cys C has the similar relevance with GFR even better when the graft function was normal and lightly renal function damaged. After transplantation, when the grafts function was damaged slightly, the Cys C had a more sensitive changement, espiacially when the Scr concentration had not increased. This indicated that the Cys C had a more sensitively and intimate correlation with GFR. Cys C, as a rapid, sensitive index, could be used in the early diagnosis of renal function damage after renal transplantation.
Significance
Our study is useful for renal transplantation in order to enhance long-term survival. It can diagnose early damagement of the draft function and help doctors to adjust the dose of immunosuppressant.
1．找到一种用于肾移植后肾功能检测的新指标，初步应用于肾移植后移植物功能的检测，并探讨其水平与移植肾功能(肾小球滤过率)的关系。
2．通过对术后半胱氨酸蛋白酶抑制剂C、血清肌酐(sCr)、尿素氮(BUN)各项指标的比较，探讨半胱氨酸蛋白酶抑制剂C作为早期肾功能损伤评估指标的应用价值。
方法：
采用回顾性分析方法，70例肾移植患者术后一月内动态监测血清肌酐、半胱氨酸蛋白酶抑制剂C，并用Modification of Diet in Renal Disease equation(MDRD公式)计算内生肌酐清除率。研究对象分为肾功能正常组(A组，31例，GFR≥90ml／min／1．73m~2)、轻度受损组(60≤GFR<90ml／min／m~2)组和肾功能中重度受损组(D组，4例，GFR<60ml／min／m~2)．依据血清肌酐正常与否，肾功能轻度受损组又分为肌酐正常组(B组，23例，Scr≤133μmol／L)和肌酐异常组(C组，12例，Scr>133μmol／L)。并与正常对照组(60例)相比较。分别绘制各组Cys C和SCr与CCr关系的散点图，并求出相关系数r。采用免疫增强散射比浊法测定半胱氨酸蛋白酶抑制剂C的水平，以流式细胞术连续检测CD4／CD8比值，ELISA检测免疫抑制剂药物浓度，评估机体的免疫状态。血生化仪测定血肌酐、尿素氮。
结果：
1．健康正常对照人群半胱氨酸蛋白酶抑制剂C的浓度是(0．72±0．13)mg／L。血清肌酐浓度为(50．48±15．20)μmol／L。
2．各组移植前半胱氨酸蛋白酶抑制剂C、血清肌酐、和尿素氮水平无显著差异(P>0．05)。
3 A组半胱氨酸蛋白酶抑制剂C浓度为(0．96±0．10)mg／L．B组半胱氨酸蛋白酶抑制剂C浓度为(1．37±0．14)mg／L．与A组对照比较有统计学差异(P<0．05)。
4．A组血清肌酐浓度为(90．51±9．86)μmol／L．B组血清肌酐浓度为(105．27±13．76)μmol／L．与A组对照比较无统计学差异(P>0．05)
5．GFR在A、B、C组与SCr、Cys C均呈直线相关，其中r分别为-0．7272和-0．7439，-0．7072和-0．7543，-0．7430和-0．7669。
结论：
Cys C浓度在肾移植术后肾功能损伤早期检测中具有重要价值。在肌酐虽然正常但CCr已经降低的患者中，其浓度已有显著变化，Cys C与肌酐清除率在肾功能正常和轻度受损患者中均呈直线相关性，其相关系数与血肌酐相比，甚至优于血清肌酐。Cystatin C单项诊断肾功能损伤时变化更明显，性能优于其他指标。由于其不受体内分解代谢，饮食等因素干扰，所以可以应用于临床，作为肾移植术后肾功能检测的常规检测指标。外周血Cystatin C检测作为一个评估移植肾功能的指标具有无创性，结果显示Cystatin C具有很高的临床应用价值，可以简便、省时、准确的应用于大量的移植患者术后移植物功能的监测。
Objects
1 To find a new index to detect the renal function after renal transplantation. This index was used in detecting the graft function. Meanwhile we rearch the relationship between Cystatin C and GFR (glomerular filtration rate).
2Through compared with Scr and BUN, to show the vulue of Cystatin C as an index in detecting the graft function after renal transplantation. And the value of cystatin C (Cys C) in the early detection of the graft function damagement after renal transplantation and providing evidence for the further diagnosis and treatment.
Methodology
At the twelfth day post-transplantation, monitored the concentration ofCys C, blood urea nitrogen (BUN) , Serum creatinine (SCr) and the glomerular filtration rate (GFR). GFR was determined by the Modification of Diet in Renal Disease equation (MDRD equation). According to the value of GFR post-transplantation, 70 cases of renal transplant patients were divided into group A (31 cases, with the normal renal function, GFR=90ml/min/1.73m~2), group B (Scr=133μmol/L, 60=GFR<90ml/min/1.73m~2, 27 cases), group C (Scr > 133μmol/L, 60=GFR<90ml/min/1.73m~2,12 cases) and group D (GFR < 60ml/min/1.73m~2, 4 cases). Meanwhile, the normal control group (n = 60) was compared. Analysis the linear correlation between Cys C, Scr and GFR through the scatterplots in each groups, and calculated the correlation coefficient(r). Determination of Cys C was performed using the Behring BN II Pro Spec analyzer. Meanwhile, used the automatic biochemistry analyzer and correlated kits to analysis the serum creatinine concentration.
Results
1. Cys C concentration in normal control group was 0.72±0.13 mg/L. Scr concentration was 50.48±15.20μmol/L.
2. The concentration of Scr, Cystatin C and BUN had no conspicuous statistically significance (P>0.05), compared with the normal control pre-transplantation.
3. Cys C concentration in group B (27 cases) were (1.37±0.14), the difference has conspicuous statistically significance (P<0.01), compared with that of group A (0.96±0.10) mg/L.
4.Scr concentration in group B (27 cases) were (105.26±13.76)μmol/L, the difference has no statistically significance (P>0.05), compared with that of group A (90.51±9.86)μmol/L.
5.Through the scatterplot, SCr and Cys C showed similar linear correlation with GFR in group A, B and C. The correlation coefficient (r) of each group was -0.7272 and -0.7439, -0.7072 and -0.7543, -0.7430 and -0.7669.
Conclusion
Cys C concentration was not influenced by diet, infection. Compared with the Scr, Cys C has the similar relevance with GFR even better when the graft function was normal and lightly renal function damaged. After transplantation, when the grafts function was damaged slightly, the Cys C had a more sensitive changement, espiacially when the Scr concentration had not increased. This indicated that the Cys C had a more sensitively and intimate correlation with GFR. Cys C, as a rapid, sensitive index, could be used in the early diagnosis of renal function damage after renal transplantation.
Significance
Our study is useful for renal transplantation in order to enhance long-term survival. It can diagnose early damagement of the draft function and help doctors to adjust the dose of immunosuppressant.
引文
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8 Kyhse2Andersen J, Schmidt C, Norclin G, et al. Serum cystatin C, determined by a rapid, automated particle2enhanced tirbidimetric method, is better marker than serum creatinine for glomerular filtration rate. Clin Chem, 1994, 40 (10): 1921 - 1926.
9 Stowe H, Lawrence D, Newman DJ, et al. Analytical performance of a particle—enhanced nephelometric immunoassay for serum cystatin C using rate analysis. Clin Chem, 2001, 47 (8): 1482 - 1485.
10 Tanaka M, Matsuo K, Enomoto M, et al. A sol particle homogeneous immunoassay for measuring serum cystatin C. Clin Biochem, 2004, 37: 27 - 35.
11 Uhlmann EJ, Hock KG, Issitt C, et al. Reference Intervals forp lasma_cystatin C in healthy volunteers and renal patients, as measured by the Dade Behring BN II system, and correlation with creatinine. Clin Chem, 2001, 47 (11): 2031 - 2033.
12 Uzuna H, KelesbMO, Ataman R, et al. Serum cystatin C level as a potentially good marker for impaired kidney function Clinical Biochemistry, 2005, 38: 792 - 798.
13 Simonsen O, Grubb A, Thysell H. The blood serum concentration of cystatinC (g—trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest, 1985, 45: 97 $ 101.
14 Bokenkamp A, Domanetzki M, Zinck R, et al. Cystatin C—a new marker of glomerular filtration rate in children independent of age and height. Pediatrics, 1998, 101 (5): 875 - 881.
15 Filler G, Priem F, Lepage N, et al. Beta2trace p rotein, cystatin C, beta (2) —micro-globulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clin Chem, 2002, 48 (5): 729 - 736.
16 Randers E, Erlandsen EJ, Pedersen OL, et al. Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function. Clin Nephrol, 2000, 54 (3): 203 - 209.
17 Newman DJ, Thakkar H, Edwards RG, et al. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int, 1995, 47 (1): 312 - 318.
18 Tomino Y, Suzuki S, Gohda T, et al. Serum cystatin C may predict the prognostic stages of patients with IgA nephropathy prior to renal biopsy. J Clin Lab Anal, 2001, 15 (1): 25 - 29.
19 Mussap M, Dalla VM, Fioretto P, et al. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int, 2002, 61 (4): 1453 - 1461.
20 Uslu S, Efe B, AlatasO, et al. Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients. J Nephrol, 2005, 18 (5): 559 - 567.
21 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 42 years follow-up study. J Am Soc Nephrol, 2005, 16 (5) : 1404- 1412.
22 Risch L, Blumberg A, Huber A. Rap id and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C. Nephrol Dial Transplant, 1999, 14 (8) : 1991 - 1996.
23 Le Bricon T, Thervet E, BenlakehalM. Changes in plasma cystatin C after renal transplantation and acute rejection in adults. Clin Chem, 1999, 45 (12): 2243 - 2249.
24 Bokenkamp A, Ozden N, Dieterich C, et al. Cystatin C and creatinine after successful kidney transplantation in children. Clin Nephrol, 1999, 52 (6): 371 - 376.
25 Herget2Rosenthal S, Trabold S, Huesing J. Cystatin C—an accurate marker of glomerular filtration rate after renal transplantation? Transpllnt, 2000, 13 (4): 285 - 289.
26 Li FK, Ho SK, Yip TP. Cystatin C assay for the detection of renal dysfunction in Chinese renaltransplant recipients. Clin Chim Acta, 2002, 322 (1 - 2): 133 - 137.
27 ShlipakMG, SarnakMJ, Katz R. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl JMed, 2005, 352 (20): 2049 - 2060.
28 Bostom AG, Bausserman L, Jacques PF, et al. Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol, 1999, 19 (9): 2241 - 2244.
29 KoenigW, Twardella D, Brenner H, et al. Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate. Clin Chem, 2005, 51 (2): 321 - 327.
30 Orlando R, MussapM, PlebaniM. Diagnostic value of plasma cystatin C as a glomerular filtration marker in decompensated liver cirrhosis. Clin Chem, 2002, 48 (6Pt1): 850 - 858.
31 Stabuc B, Vrhovec L, Stabuc2Silih M, et al. Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clin Chem, 2000, 46 (2) : 193 - 197.
32 Curhan G. Cystatin C. A marker of renal function or somethingmore? Clin Chem, 2005, 51 (2) : 293 - 294.
33 Shlipak MG, PraughtML, SarnakMJ. Update on cystatin C: new insight into the importance of mild kidney dysfunction. CurrOp in Nephrol Hypertens, 2006, 15: 270 - 275.
34 Stickle D, Cole B, Hock K, et al. Correlation of p lasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population. Clin Chem, 1998, 44 (6 Pt 1): 1334 - 1338.
35 Page MK, Bukki J, Luppa P, et al. Clinical value of cystatin C determination. Clin Chimica Acta, 2000, 297: 67 - 72.
36 Rule AD, Bergstralh EJ, Slezak JM, et al. Glomerular filtration rate estimated by cystatin C among different. Clinical presentations. Kidney Int, 2006, 69 (2): 399 - 405.
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1 Shemesh O, Globetz H, Kriss JP, et al. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int, 1985, 28: 830 - 838.
2 Swan SK. The search continues-an ideal marker of GFR. Clin Chem, 1997, 43 (6): 913 - 914.
3 RosnerMH, Bolton WK. Renal function testing. Am J Kidney Dis, 2006, 47 (1): pp 174 - 183.
4 George PM, Sheat JM. Cystatin C quantification in CSF. Clin Chem, 1989, 35 (1): 179 - 180.
5 Grubb A, Simonsen O, Sturfelt G, et al. Serum concentration of cys tatin C, factorD and beta 2-microglobulin as a measure of glomerular filtration rate. ActaMed Scand, 1985, 218 (5): 499 - 503.
6 Jiborn T, Abrahamson M, Wallin H, et al. Cystatin C is highly expressed in the human male rep roductive system. J Androl, 2004, 25 (4): 564 - 572.
7 Colle A, Tavera C, Prevot D, et al. Cystatin C level in serum of patients with human immunodeficiency virus infection. A new avidinbiotin ELISA assay for itsmeasurement. J Immunoassay, 1992, 13 (1): 47 - 60.
8 Kyhse2Andersen J, Schmidt C, Norclin G, et al. Serum cystatin C, determined by a rapid, automated particle2enhanced tirbidimetric method, is better marker than serum creatinine for glomerular filtration rate. Clin Chem, 1994, 40 (10): 1921 - 1926.
9 Stowe H, Lawrence D, Newman DJ, et al. Analytical performance of a particle—enhanced nephelometric immunoassay for serum cystatin C using rate analysis. Clin Chem, 2001, 47 (8): 1482 - 1485.
10 Tanaka M, Matsuo K, Enomoto M, et al. A sol particle homogeneous immunoassay for measuring serum cystatin C. Clin Biochem, 2004, 37: 27 - 35.
11 Uhlmann EJ, Hock KG, Issitt C, et al. Reference Intervals forp lasma_cystatin C in healthy volunteers and renal patients, as measured by the Dade Behring BN II system, and correlation with creatinine. Clin Chem, 2001, 47 (11): 2031 - 2033.
12 Uzuna H, KelesbMO, Ataman R, et al. Serum cystatin C level as a potentially good marker for impaired kidney function Clinical Biochemistry, 2005, 38: 792 - 798.
13 Simonsen O, Grubb A, Thysell H. The blood serum concentration of cystatinC (g—trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest, 1985, 45: 97 $ 101.
14 Bokenkamp A, Domanetzki M, Zinck R, et al. Cystatin C—a new marker of glomerular filtration rate in children independent of age and height. Pediatrics, 1998, 101 (5): 875 - 881.
15 Filler G, Priem F, Lepage N, et al. Beta2trace p rotein, cystatin C, beta (2) —micro-globulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clin Chem, 2002, 48 (5): 729 - 736.
16 Randers E, Erlandsen EJ, Pedersen OL, et al. Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function. Clin Nephrol, 2000, 54 (3): 203 - 209.
17 Newman DJ, Thakkar H, Edwards RG, et al. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int, 1995, 47 (1): 312 - 318.
18 Tomino Y, Suzuki S, Gohda T, et al. Serum cystatin C may predict the prognostic stages of patients with IgA nephropathy prior to renal biopsy. J Clin Lab Anal, 2001, 15 (1): 25 - 29.
19 Mussap M, Dalla VM, Fioretto P, et al. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int, 2002, 61 (4): 1453 - 1461.
20 Uslu S, Efe B, AlatasO, et al. Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients. J Nephrol, 2005, 18 (5): 559 - 567.
21 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 42 years follow-up study. J Am Soc Nephrol, 2005, 16 (5) : 1404- 1412.
22 Risch L, Blumberg A, Huber A. Rap id and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C. Nephrol Dial Transplant, 1999, 14 (8) : 1991 - 1996.
23 Le Bricon T, Thervet E, BenlakehalM. Changes in plasma cystatin C after renal transplantation and acute rejection in adults. Clin Chem, 1999, 45 (12): 2243 - 2249.
24 Bokenkamp A, Ozden N, Dieterich C, et al. Cystatin C and creatinine after successful kidney transplantation in children. Clin Nephrol, 1999, 52 (6): 371 - 376.
25 Herget2Rosenthal S, Trabold S, Huesing J. Cystatin C—an accurate marker of glomerular filtration rate after renal transplantation? Transpllnt, 2000, 13 (4): 285 - 289.
26 Li FK, Ho SK, Yip TP. Cystatin C assay for the detection of renal dysfunction in Chinese renaltransplant recipients. Clin Chim Acta, 2002, 322 (1 - 2): 133 - 137.
27 ShlipakMG, SarnakMJ, Katz R. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl JMed, 2005, 352 (20): 2049 - 2060.
28 Bostom AG, Bausserman L, Jacques PF, et al. Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol, 1999, 19 (9): 2241 - 2244.
29 KoenigW, Twardella D, Brenner H, et al. Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate. Clin Chem, 2005, 51 (2): 321 - 327.
30 Orlando R, MussapM, PlebaniM. Diagnostic value of plasma cystatin C as a glomerular filtration marker in decompensated liver cirrhosis. Clin Chem, 2002, 48 (6Pt1): 850 - 858.
31 Stabuc B, Vrhovec L, Stabuc2Silih M, et al. Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clin Chem, 2000, 46 (2) : 193 - 197.
32 Curhan G. Cystatin C. A marker of renal function or somethingmore? Clin Chem, 2005, 51 (2) : 293 - 294.
33 Shlipak MG, PraughtML, SarnakMJ. Update on cystatin C: new insight into the importance of mild kidney dysfunction. CurrOp in Nephrol Hypertens, 2006, 15: 270 - 275.
34 Stickle D, Cole B, Hock K, et al. Correlation of p lasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population. Clin Chem, 1998, 44 (6 Pt 1): 1334 - 1338.
35 Page MK, Bukki J, Luppa P, et al. Clinical value of cystatin C determination. Clin Chimica Acta, 2000, 297: 67 - 72.
36 Rule AD, Bergstralh EJ, Slezak JM, et al. Glomerular filtration rate estimated by cystatin C among different. Clinical presentations. Kidney Int, 2006, 69 (2): 399 - 405.