Serum Cystatin C

Abstract: This study evaluated the predictive value of quantitative analysis of renal arteries using three-dimensional power Doppler ultrasonography (3D-PDU) and serum cystatin C (CysC) in diagnosing fetal hydronephrosis (HN). A total of 208 fetuses with HN (a case group) and 210 healthy fetuses (a control group) were selected for this study. 3D-PDU was used to measure vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of renal arteries in newborns. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum CysC level in um- bilical cord blood. A receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic power of renal artery index and serum CysC for fetal HN. Logistic regression analysis was performed to identify risk factors for fetal HN. Compared with the control group, VI and VFI obviously decreased and serum CysC level significantly increased in the case group. The VI and VFI were positively correlated with gestational age, but negatively correlated with the disease degree of fetal HN. However, serum CysC level was positively associated with the disease degree of fetal HN. VI and VFI were negatively correlated with the disease degree of fetal HN. ROC curves indicated that the 3D-PDU showed a highest value in diagnosing fetal HN, when the optimal cut-off value of VI = 6.275 (sensitivity = 84.3, specificity = 69.7) and serum CysC = 1.745 (sensitivity = 92.8, specificity = 76.2). Logistic regression analysis indicated that fetal HN was associated with VI, VFI, and serum CysC level. These findings elucidated that fetal renal VI, VFI and serum CysC could be useful diagnostic tools for fetal HN.

Objective: To investigate the relationship between serum level of cystatin C (Cys-C) and AF (atrial fibrillation) and its clinical classification. Method: From January 2017 to April 2019, 168 cases of Xiaogan Central Hospital were chosen as the object of this study. The subjects were divided into 86 patients with AF and 82 patients in the control group. The AF group was divided into paroxysmal AF group (29 cases), persistent AF group (27 cases) and perma- nent AF group (29 cases) according to the European atrial fibrillation man- agement guidelines and the North America Society of Pacing and Electrophy- siology (NASPE) arrhythmia group organized the categorization of AF. Re- sults: Compared with the control group, the level of the serum Cys-C was significantly higher in the AF group, the difference was statistically signifi- cant ( P < 0.05). There was significant difference in Cys-C level in patients with different types of AF ( P < 0.05). The levels of neutrophil percentage, low density lipoprotein cholesterol (LDL-C), left ventricular diameter, left atrial diameter, C-reactive protein (CRP) and homocysteine in the AF group were significantly higher than those in the control group ( P < 0.05). The difference of neutrophil percentage, LDL-C, left ventricular ejection fraction, left atrial diameter, CRP and homocysteine levels in patients with different types of atrial fibrillation was statistically significant ( P < 0.05). Logistic analysis showed that the serum Cys-C level, CRP, homocysteine, left ventricular diameter, left atrial diameter could be used as an independent predictor of atrial fibrillation when other factors were corrected. Conclusion: Serum Cys-C level in atrial fibrillation group is significantly higher than the control group, there are dif- ferences between different atrial fibrillation clinical classification, its level in- creased with duration of atrial fibrillation. Serum Cys-C level and inflamma- tory markers CRP, WBC and neutrophilic granulocyte percentage were posi- tively correlated, indicating that serum cystatin C is associated with chronic inflammation, involved in the occurrence of atrial fibrillation, maintain and recurrence. Logistic analysis showed that the serum cystatin C level could be How to cite this paper: Duan, Y.Q., Xu,

Abstract: Objectives: evaluation of cystatin C level in the serum as a predictor of early renal impairment in type 2 diabetic patients. Background: the glomerular filtration rate (GFR) is often estimated from plasma creatinine. Several studies have shown that cystatin C (Cys C) can be used as a better marker for the early detection of renal function decline. Methods: patients were classified according to the urine albumin/creatinine ratio (ACR).Plasma samples were obtained from 20 healthy persons and from 40 patients with diabetes mellitus type 2 for determination of the level of creatinine and cystatin C. Results: There were no significant differences in age and sex between the three groups. However, There was a significant positive correlation between cystatin C and age, A/C ratio, HbA1c, FBS, 2HPP, DM duration and serum creatinine, and there was a significant negative correlation between cystatin C and glomerular filtration rate. eGFR was significantly lower in the macroalbuminuric group than in the micro-albuminuric and normo-albuminuric groups, and cystatin C showed the highest sensitivity and specificity in detecting micro and macro-albuminuria and accordingly early renal function decline in diabetic patients. Conclusion: from this study we concluded that serum cystatin C is a useful, practical, and non-invasive tool for early detection of renal impairment in the course of diabetes.

private laboratory in a batch within six months of blood collection. Serum cystatin C was performed using the Particle enhanced nephelometric immunoassay (PENIA) principle with cystatin C kits (Dade Behring). Should any abnormality be detected, subjects were referred to the appropriate subspecialty clinics.

subjects were healthy without severe chronic kidney dis- ease (CKD). In our study, there were consistent trends for a positive association between cystatin C levels and BMD; therefore, significant trends might have been observed if more subjects were included. On the other hand, BMI had significant positive associations with all BMDs in both sexes, and age had significant negative associations with all BMDs in women (Table 2). Furthermore, age and BMI levels were significantly increased with an increase in the serum cystatin C levels in women (Table 3). Therefore, age and BMI, as potential confounders, might account for some of the insignificant associations between cystatin C levels and risk of osteoporosis in the multiple regression analysis.

Six measurement time points (T1 preoperative, T2-4 intra- operative, T5-6 postoperative) were defined. The blood samples were stored on ice and centrifuged at 4°C at 4000 rpm for 15 minutes. The serum samples were then stored at −20°C. The analysis was performed in the central laboratory of the Centre for Internal Medicine and the study laboratory of the Department of Thoracic and Cardiovascular Surgery of Johann Wolfgang Goethe University hospitals in Frankfurt am Main (recognition according to DIN EN ISO 15189; DIN EN ISO 9001:2008 accreditations of medical laboratories). Serum cystatin C was determined by means of an immunoassay (Bühlmann, Germany). The lower limit of detection was 0.05 mg/L. The clinical parameters are based on the evaluations of the German federal cross-sector quality assurance associ- ation (SQG, Aqua Institut Göttingen, Germany) and were taken from existing postoperative databases.

In my study, the mean age group, gestational age and parity of both controls and cases was similar. Serum cystatin C concentrations were significantly higher in pre-eclamptic patients (0.895 ±0.310mg/L) compared to the healthy pregnant females (0.489 ± 0.064 mg/L) with p value of <0.001 (highly significant). Serum levels of cystatin C are increased in normal pregnancy, especially in the third trimester. This has been attributed to renal handling of low molecular weight proteins in conjunction with a decreased GFR and increased synthesis by the fetoplacental unit or generalized phenomenon.

Based on the results of this study, sCysC also do not appear to be reliable markers of renal function in non- hyperthyroid cats with azotemic CKD. The reason why sCysC do not appear to be a reliable marker of renal function in nonhyperthyroid cats is, however, unclear at this time. Although one previous small study indi- cated that sCysC are increased in cats with azotemic CKD, 8 a subsequent study calculated a reference inter- val for sCysC from healthy older cats which encom- passed serum cystatin C concentrations previously observed in many cats with azotemic CKD. 8,20 This could suggest that the sensitivity of sCysC for the detection of CKD is poor. Furthermore, 2 more recent preliminary studies have indicated that there is a poor correlation between sCysC and GFR 11 and the presence of CKD. 21 This could be secondary to altered cellular production, metabolism, renal reabsorption and elimi- nation, or elimination of cystatin C from the body via other mechanisms (for example, through the gastroin- testinal tract) in CKD. Given the results of our previ- ous study, 7 altered renal reabsorption and elimination of cystatin C could be contributory to altered sCysC in CKD and the poor performance of sCysC as a test for azotemic CKD in cats.

Abstract: Objective: To investigate the levels of serum cystatin C (CysC) and chemokine (Chemerin) in patients with diabetic retinopathy (DR) and their roles in the onset and progression of DR. Methods: A total of 150 diabetic pa- tients were enrolled as subjects and randomly divided into three groups: the proliferative DR (PDR) group (n=50), the non-proliferative DR (NPDR) group (n=50) and the control group (diabetes mellitus (DM) alone, n=50). In addi- tion, 50 healthy adults were selected as normal controls. The four groups of patients were compared in demograph- ic characteristics and biomarkers including gender, age, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high sensitive C reactive protein (hsCRP), as well as serum cystatin C and Chemerin levels. Besides, Pearson correlation analysis and Logistics regression analysis were performed. Results: The control group was associated with a significant increase in serum CysC and Chemerin levels as compared with the normal control group; the patients with PDR or NPDR showed significantly higher levels than those with diabetes mellitus (DM) alone; and the ones with PDR had significantly higher levels than those with NPDR. The serum CysC and Chemerin levels were significantly different across groups and increased with the severity of the disease (P<0.05). Pearson correlation analysis showed that the serum CysC levels were positively associated with systolic blood pressure (SBP), HbA1c, HOMA-IR, FPG, TG, TC and LDL-C (P<0.05), and the serum Chemerin levels were positively associated with BMI, HOMA-IR, urinary albumin and hsCRP (P<0.05). What’s more, the serum CysC levels were also positively associated with the serum Chemerin levels (P<0.05). Multivariate logistic regression analysis indicated that serums CysC and Chemerin were independent risk factors for DR. Conclusion: Elevated serum CysC and Chemerin levels are risk factors for DR, and they play a role in the pathogenesis of DR. Thus they are likely to become potential markers for assessment of DR.

Abstract: Objective: The present meta-analysis investigates the clinical value of two contrast-induced nephropathy (CIN) markers, serum cystatin C and creatinine, for their application as prognostic markers in percutaneous coro- nary intervention (PCI). Methods: The relevant scientific literature research databases were retrieved according to strict inclusion and exclusion criteria, and the selected studies were further screened for our meta-analysis. Statisti- cal analysis of the extracted data was performed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. Re- sults: We initially retrieved 1702 published studies and found 11 studies eligible for the current meta-analysis. The 11 selected studies contained a total of 1153 CIN patients. The results of our meta-analyses showed that serum cystatin C and creatinine levels were significantly lower in CIN patients after PCI therapy compared to those before PCI therapy (Cystatin C: SMD = -1.713, 95% CI = -2.479~-0.946, P < 0.001; Creatinine: SMD = -0.499, 95% CI = -0.856~-0.142, P = 0.006). In support of their clinical value to PCI, the estimated glomerular filtration rate (eGFR) was not significantly different in CIN patients before and after PCI therapy (SMD = -0.036, 95% CI = -0.499~0.427, P = 0.879). Ethnicity-based subgroup analysis clarified that serum cystatin C levels were significantly lower in CIN patients after PCI therapy, in comparison to before PCI therapy, in Asians (SMD = -2.196, 95% CI = -3.262~-1.131, P < 0.001), but such correlation was not observed in Caucasians (SMD = -0.574, 95% CI = -1.170~0.022, P = 0.059). Conclusion: Our study findings strongly support that serum cystatin C and creatinine levels can predict the success of PCI in Asian CIN patients, and PCI has no significant influence on eGFR.

glomerular filtration [8-11]. Moreover, its concentration is not influenced by infections, liver diseases, or inflammatory dis- eases. Use of serum cystatin C as a marker of GFR is well doc- umented, and some authors have suggested that it may be more accurate than serum creatinine for this purpose [12-19]. The difficulties associated with monitoring and evaluating GFR in critically ill individuals are well known. Thus far no studies evaluating serum cystatin C as a marker of GFR in these patients have been reported. The aim of the present study were to determine the accuracy of serum cystatin C concen- tration as a marker of GFR in critically ill individuals.

SCysC is recognized to be far less influenced by muscular mass than SCr [4]. Not surprinsingly, SCysC has been vali- dated as a superior GFR biomarker to detect chronic kid- ney disease (defined as GFR below 60 mL/min/1.73 m 2 ) in several specific populations with decreased or abnormal muscular mass like in the elderly, cirrhotic patients, renal transplant patients, and patients suffering from anorexia nervosa [3,13,17]. Herein, we extend this notion to critically ill patients. Numerous previous studies performed in se- verely ill patients (not necessarily hospitalized in ICU) have suggested the better performance of SCysC for detecting AKI [5,6]. However since most of those studies did not pro- vide a reference GFR measurement against which SCr and SCysC could be thoroughly compared, the real added value of SCysC as a marker of GFR has remained partly specula- tive [6]. Among all these studies, only two of them realized after cardiac surgery have measured GFR by a reference method (iohexol or 51 Cr-EDTA) and showed superior per- formance of cystatin C [18,19]. Focusing specifically on crit- ically ill patients, Le Bricon et al. measured GFR by a reference method ( 51 Cr-EDTA) and showed a better correl- ation between 1/cystatin C and GFR than between 1/cre- atinine and GFR (r = 0.755 versus r = 0.686). The authors also demonstrated a better sensitivity-specificity of cystatin C to detect impaired GFR [20]. However, the number of pa- tients included in this study was very limited (n = 15). In addition, in this study, the 51 Cr-EDTA clearance was

Measurements of serum CysC, C1q, Urea, and Creat Serum CysC, C1q, Urea, and Creat were measured using the fully automatic analyzer Labospect™ 008 (Hitachi, Japan). CysC and Urea kits were provided by Sichuan Mac- cura Biotechnology Co., Ltd. (Sichuan, China). C1q kits were obtained from Shanghai Beijia Chemical Reagent Co., Ltd. (Shanghai, China), and Creat kits were purchased from FUJIFILM Wako Pure Chemical Co., Ltd. (Osaka, Japan). Controls were respectively provided by Bio-Rad (Hercules, CA, USA); Sichuan Maccura Biotechnology Co., Ltd.; and Shanghai Beijia Chemical Reagent Co., Ltd. CysC was mea- sured by turbidimetric immunoassay, and Urea and Creat were detected by the urease method and the sarcosine oxidase assay, respectively. Enzyme-linked immuno- sorbent assay (ELISA) is the frequently used method for C1q measurement. However, it has poor repeat- ability for quantitative detection. In this work, serum C1q levels were directly determined by automated immunoturbidimetric analysis. Compared to ELISA assays, its detection speed is much higher, and less interference and low cross-contamination between samples are observed.

During inflammatory processes, Cystatin C release is down-regulated, contributing to increased cysteine protease activities in the macrophage microenvironment. (Chapman HA Jr, 1990) 36 . Cyst C is a powerful inhibitor of cathepsins S and L. High levels of Cyst C are detectable in class II-positive lysosomes of immature dendritic cells (DCs) and Langerhans cells. The maturation process of DCs leads to reduced levels of cyst C, and allows the up-regulation of cysteine proteases cathepsins L and S. For this reason, it has been suggested that Cyst C plays a role in the intracellular control of invariant chain (li) degradation and antigen presentation. (Pierre P,1998) 37 . Members of the three Cystatin families have been shown to up-regulate the release of nitric oxide (NO) from IFN-gamma activated macrophages (Verdot L,1996, Hartmann S,2002,) 38,39 . NO has been demonstrated to induce a strong inhibition of lymphocyte proliferation in vitro and to modulate cytokine gene expression in various cell type.(Marletta 1993) 40 . It is important to note that Cystatin induced up-regulation of NO release by activated macrophages is stimulated via the synthesis of TNF-alpha and IL-10 .( Kolb.H. 1992) 41 .

Our study expands upon previous work because it ac- counts for other clinically relevant non-GFR factors in the predictive model, including the use of a vancomycin loading dose and the total dose given prior to the trough level. As expected, loading doses were not associated with predicted vancomycin trough since troughs were measured under steady-state conditions. Although vanco- mycin loading has the theoretical pharmacokinetic benefit of expediting the time to a higher serum drug concentra- tion and potential clinical effect (not measured in this study), our study detected no impact of loading on steady- state blood levels among the 37% of patients in whom one was used [41]. Drug dosing recommendations by the US Food and Drug Administration and those used in clinical practice are based largely on GFR estimates expressed in

Several recent publications have demonstrated that cystatin is superior to serum creatinine or creatinine-based estimating equations for prediction of all- cause mortality, cardiovascular events and incident congestive heart failure in cohorts that were predominantly free of cardiovascular disease at inception (17, 27-30). Furthermore, in our study the possibly important prognostic value of cystatin among patients with PCOS has also been suggested and it might be a useful clinical marker providing complementary information to establish risk determinants.

cardiac function after EECP might have led to improved nutritional status and masked the small improvement in renal function when serum Cr is used as a marker. Previ- ous studies have suggested that Cys C is a more accurate and sensitive marker of GFR compared to Cr in dia- betic and non-diabetic patients [31] as well as being less influenced by age, gender, weight, dietary protein intake and muscle mass, which obscure changes in Cr-based GFR [32,33]. Moreover, changes in Cys C levels can be used to more accurately predict changes in GFR than changes in Cr [34]. Thus, Cys C was used to evaluate renal func- tion in the study. Although Cys C is less dependent on factors such as age, sex, race and body mass index when compared to creatinine-based GFR estimation, it can be affected by other factors such as body composition (lean mass), thyroid dysfunction, cancer and left ventricular mass [35-38]. It is possible that GFR –independent factors could account for decreases in serum cystatin in some individ- uals, but these factors were not apparent during the follow-up of our patients and were unlikely to account for the changes in serum cystatin C in the group as a whole. In addition, we evaluated the effects of EECP on renal function using GFR estimating equation which employed Cys C in combination with Cr, age, sex and race [10]. This equation has recently been shown to be more accurate than equations using either marker alone [10,39,40] and has been recommended as the optimal equation by experts for assessing CKD [40].

decreases. All of these factors explain why serum creatinine concentration may not be a good parameter for accurate determination of GFR, especially at lower rates (Levey et al., 1988). Cystain C production in the body is a stable process that is not influenced by renal conditions, increased protein catabolism, or dietetic factors. Moreover, it does not change with age or muscle mass like creatinine does. Its biochemical characteristics allow free filtration in the renal glomerulus, and subsequent catabolism by the proximal tubules. For these reasons, serum cystatin C has been suggested to be an ideal endogenous marker of GFR (Finnney et al., 2000; Herget- Rosenthal et al., 2000; Risch et al., 2001). In the present study, the mean serum creatinine in the 40 critically ill patients was 1.34 mg/dL which is slightly increased than the upper limit of normal (1.2 mg/dL) and the mean serum creatinine in the group of patients with creatinine clearance M 80 mL/min per 1.73 m 2 also slightly elevated to 1.48 mg/dL. On the other hand the mean serum cystatin C in the 40 critically ill patients was 2.8 mg/L which is about double the upper limit of normal (1.5mg/dL); and the mean serum cystatin C in the group of patients with Cr C <80mL/min/1.73 m 2 was 3.3 mg/L which is more than double the upper limit of normal (1.5 mg/L). In the group of patients with Cr C >80mL/min/1.73 the serum creatinine was within normal 1.02mg/dL while serum cystatin C was elevated to 1.64 mg/L which is more than the upper limit of normal (1.5 mg/L). This finding indicate that serum cystatin C detetmild and moderate acute kidney injury better than serum creatinine. Our results coincide with that reported by (Coll et al., 2000; Grubb and Cystatin, 2000; John et al., 2003; Delanaye et al., 2004). These authors reported that cystatin C values was abnormally high when GFR decreases to 88 mL/min per 1.73 m 2 (Coll et al., 2000; John et al., 2003). Therefore, cystatin C could detect renal dysfunction one to two days before creatinine (Herget Rosenthal et al., 2004). some authors reported that cystaine C was also superior tp cretinine in the children and patients with muscle loss (Le Bricon et al., 2005; Filler et al., 2005) We found CrC less than 80 mL/min per 1.73m 2 in 70% of critically-ill patients which is similar to other studies (8,11). All our patients were ale, but other studies find gender differences in cystatin C levels (Hoste et al., 2005; John et al., 2003; Kezama et al., 2009; Foster et al., 2006).

As serum Cystatin C(Cys), a more accurate predictive biomarker of glomerular filtration rate (GFR), and neu- trophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of AKI, have been successfully used in the liver diseases and LT studies [4,6,18-22], we approached to investigate the changes of renal RI values during anhepatic stage and early neohepatic stage as well as the Cys, NGAL after reperfusion in a rat liver transplantation model. This investigation might gene- rate new insights into the response of the kidney to potential harmful factors during the early reperfusion and raise the concern into the diagnostic value of RI measurements alone.

glomerular filtration rate, meaning that increase in cystatin- C leads to reduced glomerular filtration rate. The increase in cystatin-C could be attributed to the toxic effect of gas flared constituents. These constituents serve as secondary metabolites which are generated during oxidation of benzene and benzene-like compounds by cytochrome P450 enzymes that are well known electrophiles which readily react with peptides, proteins, DNA and forms protein adducts. The formation of these metabolites have been identified in parallel with poly aromatic hydrocarbon (PAH) exposure, and the formation of these adducts might provide a more accurate assessment of PAH exposure and potential nephrotoxicity. The analysis of serum cystatin-C showed a gender difference with females having a higher level than the male which negates an earlier position by Adamu (2015) [2] and Knight et al. (2004) [21] which reported that cystatin-C levels are not statistically affected by gender but agrees with Okonkwo et al. (2015) [33] that noted an increase in serum cystatin-C in females compared to the males.