Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats

Cystatin C, a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the urinary and plasma levels of cystatin C and how useful they are for the early detection of acute kidney injury (AKI) in CDDP-treated rats in comparison with other biomarkers (β2-microglobulin, calbindin, clusterin, EGF, GST-α, GST-μ, KIM-1, NGAL, osteopontin, TIMP-1, and VEGF). The urinary levels of cystatin C, GST-α, KIM-1, and EGF changed prior to proximal tubule damage and increases in plasma urea nitrogen and creatinine levels, suggesting their usefulness for predicting AKI. On the other hand, the plasma cystatin C level hardly changed. We also investigated the localization of cystatin C in the kidney according to the progression of renal damage. Cystatin C was predominantly localized in the proximal tubule of the cortex, and its immunohistochemical expression was not affected by CDDP treatment. In addition, cystatin C was observed in the lumen of the renal tubule in the cortex, cortico-medullary junction, and medulla during the progression of renal damage, although its immunoreactive area ratio was very low.In conclusion, urinary cystatin C measurements can detect CDDP-induced AKI as early as KIM-1, GST-α, and EGF in rats, although the change ratio of the cystatin C was smaller than others. Immunohistochemical cystatin C expression in the proximal tubule of the kidney was hardly changed by the CDDP treatment, but it was newly observed in the renal tubule lumen after CDDP treatment.     

血清胱抑素C对冠心病患者预后评估的价值

目的：探讨血清胱抑素C水平对冠心病患者预后评估中的作用。方法：选择住院且经冠脉造影等检查确诊的冠心病患者共142例,其中不稳定性心绞痛患者72例,稳定性心绞痛患者70例,并选造影正常者65例作为对照,用免疫比浊法测定血清胱抑素C浓度,对所有患者随访1年,记录主要心血管不良事件发生情况。统计分析血清胱抑素C与主要心血管不良事件的关系。结果：冠心病患者血清胱抑素C水平与主要不良心血管事件(major adverse cardiac vascular events,MACE)总事件相关,相关系数r值为0.43(P<0.05)。结论：血清胱抑素C水平可作为预测冠心病患者MACE事件的一个评价指标。     

Paraoxonase activity and paraoxonase 1 gene polymorphism in patients with uremia

Patients on hemodialysis (HD) show an increased risk for developing atherothrombotic events. The oxidative modification of low density lipoproteins (LDL) play an important role in the pathogenesis of atherosclerosis. In patients with uremia (chronic renal failure and HD), the increased oxidative stress induces oxidative modification of LDL. High density lipoproteins (HDL) exhibit a double antiatherogenic role, removing both lipid peroxides from LDL and cholesterol from tissues or vascular wall. Paraoxonase 1 (PON1) is one of three enzymes shown to prevent the formation of oxidized LDL. PON1 activity is modulated by its genetic polymorphism and by non-genetic factors, such as diet, smoking, acute phase reactants, and hormones. PON1 activity has been found to be significantly decreased in uremia. The present study aimed to verify the possibility that this reduced activity could be caused by a different PON1 gene polymorphism between patients on HD and healthy subjects, but this was not the case. The main cause may be identified in the different distribution of HDL subspecies, rather than in the different PON1 allele distribution between healthy subjects and patients with uremia.     

Plasma Cystatin C in the Dog: Reference Values and Variations with Renal Failure

Cystatin C is a low-molecular-mass acid protein produced at a constant rate by all nucleated cells and cleared by glomerular filtration. In human medicine it is considered to be a better indicator of renal failure than creatinine. Plasma (Pl-) cystatin C measurements in 179 clinically healthy dogs, using an immunoturbidimetric procedure for human cystatin C, showed a Gaussian distribution with an upper limit of 1.3 mg/l. There were no differences between the sexes. Pl-cystatin C was slightly lower in 1–8-year-old adults than in younger or older dogs. It was also lower in dogs weighing less than 15 kg than in heavier ones. Meals produced a dramatic decrease in Pl-cystatin C that lasted for up to 9h. Pl-cystatin C was elevated in 98% of dogs with renal insufficiency, even in some cases where the Pl-creatinine was normal. Cystatin C may therefore be a useful indicator of renal insufficiency in clinically relevant dogs with borderline P1-creatinine values.     

Evaluation de la fonction glomérulaire par le dosage de la cystatine C. Absence d'influence de l'état nutritionnel

Cystatin C measurement for the assessment of glomerular filtration rate. Cystatin C is a non-glycosylated basic protein that is produced by all nucleated cells, filtered by the glomerular membrane and catabolized in the proximal tubular cells. Its serum concentration is influenced by age, in parallel with changes in glomerular filtration rate. We evaluated cystatin C, creatinine and renal function in patients with head and neck tumors before administration of chemotherapy with cisplatin. Results showed a relationship between cystatin C and creatinine, cystatin C and age. There was no correlation between cystatin C and nutritional status (albumin and prealbumin) of patients. These preliminary findings suggest that cystatin C could provide information in patients with denutrition to evaluate renal function.     

血清胱抑素C水平与不稳定型心绞痛严重程度的相关性

目的探讨血清胱抑素C水平与不稳定型心绞痛（unstable angina,UA）严重程度的相关性.方法 选取本院不稳定型心绞痛患者147例作为观察组（按Braunwald分级分为三个亚组）,选取同期非冠心病患者50例作为对照组,对四组的血清胱抑素C水平进行检测,并进行比较分析.结果 观察组各亚组血清胱抑素C水平及阳性率明显高于对照组;观察组亚组中血清胱抑素C水平及阳性率,BraunwaldⅢ级组患者明显高于BraunwaldⅡ级组和Ⅰ级组患者,BraunwaldⅡ级组患者亦明显高于Braunwald Ⅰ级组患者,差异均有统计学意义（P＜0.05）.结论 血清胱抑素C水平随着不稳定型心绞痛严重程度的加重而升高,检测血清胱抑素C对不稳定型心绞痛严重程度具有一定的预测价值,有助于判断病情,指导治疗.     

Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats

The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis.Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage.In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent.     

Urinary cystatin C as a biomarker for diabetic nephropathy and its immunohistochemical localization in kidney in Zucker diabetic fatty (ZDF) rats

Cystatin C, a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the usefulness of urinary cystatin C for the detection of diabetic nephropathy in Zucker diabetic fatty (ZDF) rats compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF). Urinary levels of cystatin C were increased in ZDF rats where renal damage was not histopathologically observed, and then further increased with the progression of renal damage, demonstrating the usefulness of early detection and accurate assessment of diabetic nephropathy. Urinary β2-microglobulin, clusterin, GST-μ, KIM-1, and osteopontin had the potency to detect renal damage in ZDF rats as well as cystatin C.We also investigated immunohistochemical localization of cystatin C in the kidney according to progressive renal damage. Cystatin C expression was mainly observed in the proximal renal tubule in ZDF rats, and hardly changed with progression of nephropathy. When renal damage was remarkable, cystatin C expression was also observed in the tubular lumen of the cortex and medulla, which was considered to be characteristic of renal damage in diabetic nephropathy.In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-μ, KIM-1, and osteopontin could be useful biomarkers of diabetic nephropathy in ZDF rats. Immunohistochemical cystatin C expression in the proximal renal tubule was hardly changed by the progression of diabetic nephropathy, but it was newly observed in the tubular lumen when renal damage was remarkable in ZDF rats.     

胱抑素C临床检验及对诊断肾脏疾病的临床价值

胱抑素C也被称为γ-微量蛋白或γ-后球蛋白,由人体核细胞产生,肾小球滤过而被清除,正常生理状态下血清胱抑素C水平恒定。胱抑素C的临床检测实现了自动化、标准化、检验结果的可比性,所以目前它是一个最好、最有效反映肾小球滤过功能的标志物。本文对胱抑素C临床检验及在肾脏疾病中的研究进展进行综述。     

半胱氨酸蛋白酶抑制剂C与肾移植后尿路梗阻患者的肾功能

背景：半胱氨酸蛋白酶抑制剂C不被肾小管分泌和重吸收,近年来被认为是一种非常理想的评价肾小球滤过率的指标。 目的：探讨肾移植后输尿管狭窄患者血清半胱氨酸蛋白酶抑制剂C水平变化及其在肾功能损伤诊断中的价值。 方法：选取2007年4月至2011年4月于深圳市第二人民医院泌尿外科及广州华侨医院泌尿外科行肾移植并于移植后发生输尿管狭窄伴肾功能不全的患者18例作为病例组,同时纳入同期年龄性别与病例组相匹配的健康体检者63名作为对照组。分别于输尿管狭窄治疗前及治疗后1个月测定患者血清半胱氨酸蛋白酶抑制剂C、肌酐、尿素氮水平并分析其相关性。 结果与结论：与对照组比较,病例组输尿管狭窄治疗前半胱氨酸蛋白酶抑制剂C、血肌酐和尿素氮水平均显著增高(P < 0.01);治疗后1个月,病例组半胱氨酸蛋白酶抑制剂C、血肌酐和尿素氮水平较治疗前显著降低(P < 0.01)。相关分析结果显示,肾移植后输尿管狭窄患者血清半胱氨酸蛋白酶抑制剂C水平与血肌酐和尿素氮水平呈正相关。提示血清半胱氨酸蛋白酶抑制剂C可作为肾移植后肾功能恢复情况的监测指标。     

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy

Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment. A retrospective study was performed using the liver biopsy specimens obtained before IFN treatment from 69 patients with chronic serotype 1 hepatitis C virus (HCV) infection. TRX and TBP-2 mRNA levels in the liver biopsy specimens were amplified by real-time RT-PCR. The serum TRX protein level was estimated with a sandwich enzyme-linked immunosorbent assay kit, and the expression of TRX protein in the liver was examined immunohistochemically in 19 patients. There was no association between the serum TRX level and the TRX level in the liver. There was a significant correlation between the expression level of TRX protein in the liver and the TRX mRNA level in the liver. TRX and TBP-2 levels in the liver tended to decrease slightly with increased fibrosis stage, although not significantly. The TRX level in the liver tended to increase with hepatitis activity index, although not significantly. TBP-2 mRNA levels in the liver were significantly higher in responders than non-responders to the IFN therapy (p<0.05). Among patients who had a high viral load of >850 KIU/ml, the TRX level in the livers of non-responders was significantly lower than that in the livers of responders (p<0.05). TRX and TBP-2 mRNA levels in the liver before IFN therapy may predict the outcome of IFN therapy in patients with chronic serotype 1 HCV infection.     

初次单侧全膝关节表面置换者肾功能的变化

背景：全膝关节表面置换中植入假体系统、围手术期血流动力学的改变、药物等均可能对患者肾功能产生影响。 目的：动态观察膝关节表面置换术围手术期相关处理对患者肾功能的影响。 方法：纳入膝关节表面置换患者42例,检测患者置换前后血清肌酐、胱抑素C及尿微量白蛋白水平,比较置换前后患者肾功能。 结果与结论：42例患者全膝关节表面置换均成功,在置换后1个月内未发生少尿、无尿、大量蛋白尿、肾衰竭等严重的肾脏并发症。围手术期血清肌酐水平未发生明显变化;胱抑素C水平在置换后1周内无明显变化,而在置换后1个月,较置换前下降;尿微量白蛋白水平在置换后1 d上升,自置换后3 d开始呈下降趋势,置换后7 d、1个月尿微量白蛋白水平均较置换前降低。结果说明,全膝关节表面置换对患者肾功能仅产生了轻度的一过性损伤,并且置换后1个月患者肾功能平均水平得到改善。对初次行单侧膝关节表面置换患者,围手术期积极恰当的临床处理,不致对肾功能产生严重损伤。     

Evidence for lipid peroxidation in obstructive sleep apnea

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with an increased rate of cardiovascular morbidity, which has been suggested to be related to oxidative stress. The present study investigated the concentration of lipid peroxidation biomarkers in patients with OSA in comparison with nonapneic controls and the effects of treatment with nasal continuous positive airway pressure (nCPAP) on these biomarkers. DESIGN: In Experiment 1, morning plasma levels of the oxidative-stress biomarkers, thiobarbituric reactive substances (TBARS) and peroxides (PD), and of the antioxidant protective enzyme paraxonase-1 (PON1), were measured in OSA patients with and without cardiovascular disease (CVD) and in nonapneic controls after an overnight fasting. The concentrations of the biomarkers were compared between patients and controls and were correlated with respiratory disturbance index (RDI). In Experiment 2, TBARS and PD were measured at hourly intervals during sleep in sleep-apnea patients before and after nCPAP treatment as well as in controls. PATIENTS: In the first experiment, 114 consecutive patients with sleep apnea, 55 without (+OSA/-CVD) and 59 with CVD (+OSA/+CVD), and 30 nonapneic controls were investigated. Nine patients and 6 controls participated in Experiment 2. Five of the patients were also studied 9.3 +/- 3.9 months after nCPAP treatment. MEASUREMENTS AND RESULTS: Morning levels of TBARS and PD were found to be significantly higher in both groups of OSA patients than in controls. The PON1 was lower in +OSA/+CVD patients than in controls and +OSA/-CVD patients, but the difference between the 2 OSA groups bordered on statistical significance. The concentrations of TBARS and PD were significantly positively correlated with RDI (.43, P < .0001 and .36, P < .0002, respectively), while a negative correlation was found between RDI and PON1 activity (-.24, P < .01). Stepwise regression analysis revealed that RDI was an independent significant predictor of all 3 lipid-peroxidation biomarkers. In the second experiment, nocturnal levels of TBARS and PD were significantly higher in sleep-apnea patients than in controls and were significantly lowered by nCPAP treatment. CONCLUSIONS: These results support the existence of an increased state of oxidative stress in OSA and its possible involvement in cardiovascular morbidity.     

Cystatin C: a promising marker and predictor of impaired renal function

Cystatin C is a relatively stable protein in serum and heparinized plasma that shows promise as a convenient measure of glomerular filtration rate (GFR). However, it is becoming clear that the relationship between cystatin C and GFR can depend on the clinical presentation. Factors influencing cystatin C levels are those that affect the rate of synthesis of the protein, such as thyroid status and the use of steroids. As with all laboratory tests, results should be interpreted in the light of the method's known limitations and in conjunction with other clinical and laboratory information. Nevertheless, accumulating evidence suggests that cystatin C is a useful biomarker for renal function, and may even be the method of choice in a range of clinical situations, from GFR surveillance in diabetics to the assessment of acute kidney injury in critically ill patients.     

Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation

The colocalization of cystatin C, an inhibitor of cysteine proteases, with amyloid beta (Abeta) in parenchymal and vascular amyloid deposits in brains of Alzheimer's disease (AD) patients may reflect cystatin C involvement in amyloidogenesis. We therefore sought to determine the association of cystatin C with Abeta. Immunofluorescence analysis of transfected cultured cells demonstrated colocalization of cystatin C and beta amyloid precursor protein (betaAPP) intracellularly and on the cell surface. Western blot analysis of immunoprecipitated cell lysate or medium proteins revealed binding of cystatin C to full-length betaAPP and to secreted betaAPP (sbetaAPP). Deletion mutants of betaAPP localized the cystatin C binding site within betaAPP to the Abeta region. Cystatin C association with betaAPP resulted in increased sbetaAPP but did not affect levels of secreted Abeta. Analysis of the association of cystatin C and Abeta demonstrated a specific, saturable and high affinity binding between cystatin C and both Abeta(1-42) and Abeta(1-40). Notably, cystatin C association with Abeta results in a concentration-dependent inhibition of Abeta fibril formation.     

Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?

Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000? (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients.     

Serum Cystatin C is a Potential Endogenous Marker for the Estimation of Renal Function in Male Gout Patients with Renal Impairment

Serum creatinine level is the most commonly used indices for assessment of glomerular filtration rate (GFR), even though these indices have been shown to have some limitations in clinical practice. We investigated the diagnostic efficacy of serum cystatin C compared to that of serum creatinine levels and identified the relating factors associated with changes in serum cystatin C levels in gout patients with renal impairment. A total of 68 gouty patients with renal impairment were enrolled in this study. Diagnostic efficacy of serum cystatin C levels was evaluated through non-parametric receiver operating characteristic (ROC) analysis. The risk factors for changes in serum cystatin C levels were confirmed using multivariate regression analysis. With 24-hr urine creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702, P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the clinical parameters for increased serum cystatin C are a higher stage of chronic kidney disease, older age, use of allopurinol, and lower high density lipoprotein-cholesterol. The area under the curve (AUC) at ROC plots identified that of serum cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C is a reliable endogenous marker for the assessment of renal function or GFR in gout patients with renal impairment.     

Comparison of renal function markers in Kuwaiti patients with sickle cell disease

BACKGROUND: Proteinuria is a common manifestation of renal disease which is a significant cause of morbidity in patients with sickle cell disease (SCD). OBJECTIVE: To evaluate and compare cystatin C, beta(2)-microglobulin, and creatinine as markers of renal disease in relation to the degree of proteinuria and other complications of SCD. METHODS: 24 h urine collections were used for estimation of urine protein and creatinine clearance in 59 patients with SCD. Results were correlated with plasma cystatin C, beta(2)-microglobulin, creatinine, glomerular filtration rate (GFR; derived from plasma creatinine by Cockcroft-Gault, MDRD formulae, and calculated cystatin C clearance), and clinical and haematological variables. RESULTS: Comparing the different methods of GFR, the proportion of patients with hyperfiltration (GFR >140 ml/min) were 30.5% (MDRD), 44.1% (Cockcroft-Gault), and 10.2 % (calculated cystatin C clearance). Cystatin C was the most consistent marker of hyperfiltration. The endogenous markers of GFR showed an increasing trend with increasing proteinuria, but haematological variables were not correlated with cystatin C, beta(2)-microglobulin, or plasma creatinine. Urine protein excretion was correlated with age (r = 0.33) and significant proteinuria was present in 13.6% of patients. Patients with proteinuria had lower haemoglobin concentration (p = 0.027) than those without proteinuria but HbF was not related to the degree of proteinuria or to markers of GFR. CONCLUSIONS: Markers of GFR show variable ability to identify hyperfiltration in patients with SCD, but cystatin C is the best endogenous marker. Proteinuria is associated with age, haemoglobin, and abnormalities of GFR. Routine screening is recommended to allow for early detection and intervention.     

A Meta-analysis on diagnostic value of serum cystatin C and creatinine for the evaluation of glomerular filtration function in renal transplant patients

Objectives

This meta-analysis aimed to perform a systematic review on comparing the diagnostic value of serum cystatin C and creatinine for glomerular filtration rate in renal transplant patients.

Methods

The data was extracted into 2×2 table after the articles were assessed by the tool of QUADAS and heterogeneity analysis. The SROC curve and meta-analysis were performed by MetaDisc1.4.

Results

Meta-analysis showed that the serum cystatin C had no heterogeneity (P=0.418, I2=2.2%, DOR=25.03), while creatinine heterogeneity was high (P=0.109, I2=37.5%, DOR=9.11). The values of SEN, SPE and SAUC were calculated as 0.86, 0.70 and 0.9015 for cystatin C, and 0.78, 0.73 and 0.8285 for creatinine individually. This study utilized GFR detection and subgroups analysis by cutoff. The PLR was 6.13 and the NLR was 0.12 for cystatin C, compared to SCr (3.72, 0.32). There was homogeneity among these studies using PENIA testing for cystatin C (χ2=2.61, P=0.4560, I2=0.0%.

Conclusions

There were significant correlations among cystatin C , creatinine and glomerular filtration rate (GFR). Cystatin C had more sensitivity but less specificity than creatinine for evaluation of GFR. Cystatin C had strong ability in diagnosing renal function after renal transplant and ruling out diagnostic efficacy.     

Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m(2) estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m(2) estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.