CysC Concentration Research Articles

Establishment of age/gender-related serum cycstatin C reference intervals in children by transmission turbidimetry

Objective To establish pediatric serum CysC reference intervals based on the children's hospital laboratory data in Zhejiang Province and analyse the effects of CysC levels on age and gender. Methods CysC was one of tests of a routine biochemical screening panel employed for most outpatients and inpatients in the children's hospital, and 8 127 subjects (4 264 boys and 3 863 girls) were selected from 13 567 subjects from laboratory information system according to the exclusion criterion with seriously systemic diseases, cardiovascular diseases, kidney diseases, elevated values of creatinine, urea or ALT for which 1.5-fold upper limit, serum samples with hemolysis, icterus or lipid turbidity, same patients with non-first-time CysC results and living addresses which were not in Zhejiang. The serum CysC was determined by transmission turbidimetry on Roche DPP modular automatic biochemical analyzer. SPSS 17.0 software and EXCEL 2003 were employed for statistical analysis in this study. Results The serum CysC concentration was a Gaussian distribution after log transformation. The mean Log-transformated CysC lg (CysC) concentration of boys in five age groups ( ＜ 1 month, 1 to 3 months, 4 to 11 months, 1 to 2 years and 2 to 16 years) were 0. 224,0. 170,0. 112,0. 061, -0. 011 (mg/L,lg) respectively, and the mean Log-transformated CysC lg(CysC) concentration of girls in five age groups were 0. 222, 0. 164, 0. 089, 0. 057,-0. 010 ( mmg/L, lg) respectively, and no statistically significant differences between Ig( CysC ) and gender in five age groups were found ( t values were 0. 174, 0. 362, 0. 445, - 1. 464 and - 0. 093, respectively,and corresponding P values all were greater than 0. 05 ). The mean lg ( CysC ) concentrations in five age groups were 0. 222,0. 166,0. 100,0. 059, - 0. 010 ( mmg/L, lg), and significant differences between Lg ( CysC ) and ages by Analysis of Variance were observed ( F = 309. 785 and P = 0 in between-groups totally,P = 0 in any two groups). Serum CysC levels were highest in the age of ＜ 1 month, then declined to the age of 2 years and kept stable in the age of 2 to 16 years. The serum CysC reference intervals for children were as follows:0. 95 -2. 92 mg/L in the age of ＜ 1 month, 0. 81 -2.67 mg/L in the age of 1 to 3 months, 0. 65 -2.45 mg/L in the age of 4 tol2 months, 0. 56 -2. 35 mg/L in the age of 1 year and 0. 45 -2. 13 mg/L in the age of 2 to 16 years. Conclusions There is no significant effect on pediatric CysC levels with gender but close correlated with age below 2 years old. It is necessary to establish appropriate age-related reference intervals of serum CysC for efficiently evaluating renal function in local children. Key words: Cystatin C ; Reference interval; Data mining; Transmission turbidimetry; Pediatrics

Measurements of serum cystatin C concentrations underestimate renal dysfunction in pediatric patients with chronic kidney disease

In our clinical experience, cystatin C (CysC) concentrations are not as high as expected in patients with chronic kidney disease (CKD) and high-stage renal dysfunction. We therefore investigated whether measurements of serum CysC result in an underestimation of renal dysfunction in pediatric patients with CKD. Glomerular filtration rate (GFR) was estimated from serum creatinine (Cr) concentration, using the equation Cr-GFR (%)=[0.30×body length (m)/serum Cr]×100; and from serum CysC concentration, using the equation Cys-GFR (%)=(0.70/serum CysC)×100. We investigated the relationship between GFR estimated by these 2 equations. Patients aged 2-12years were assorted into 5 groups, based on GFR-Cr categories of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75%, and GFR-CysC/GFR-Cr ratios were compared in these 5 groups. The median GFR-CysC/GFR-Cr ratio in groups of patients with GFR-Cr of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75% were 2.28, 1.48, 1.22, 1.18 and 0.98, respectively, with statistically significant differences between any two groups (p<0.001). Measurements of serum CysC concentrations lead to underestimation of renal dysfunction in pediatric patients with CKD.

Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08–5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.

Cystatin C, cardiometabolic risk, and body composition in severely obese children

The aim of this study was to assess the relationship between cystatin C (CysC), cardiometabolic risk factors (CMRFs), and body composition in severely obese children. We evaluated 117 children aged 7-14 years old. Seventy-nine of these were severely obese (body mass index z-score ranging from 2.1 to 8.4), and 38 were children with normal nutrition state. CysC was determined by immunonephelometry. CMRFs (glucose, insulin, high-density lipoprotein cholesterol, triglycerides, homocysteine, uric acid, alanine aminotransferase, and high-sensitivity C-reactive protein) were measured by standard biochemical methods. Blood pressure was evaluated at the clinical examination. Renal function was estimated using the glomerular filtration rate (eGFR) based upon creatinine levels, and body weight (Léger formula). Body composition was assessed by segmental bioelectrical impedance. Obese children at the highest tertile of CysC values were characterized by their aggregation of CMRFs. CysC concentration was associated with insulin resistance, alanine aminotransferase, uric acid, and homocysteine after adjusting for age, gender, and eGFR. CysC values were also correlated with the fat-free mass and specifically with skeletal muscle mass. CysC levels were correlated with CMRFs factors independently of renal function, and affected by skeletal muscle mass in severely obese children, although they are less influenced by this than is creatinine.

Serum cystatin C for estimation of residual renal function in children on peritoneal dialysis

Residual renal function (RRF) is an important parameter in the management of patients on chronic dialysis. The aim of this cross-sectional study was to determine the efficacy of serum cystatin C (CysC) for RRF estimation in 20 children (16 boys, 4 girls; median age 13.4 years) undergoing peritoneal dialysis (PD). For studies of correlation with serum CysC, the average of creatinine clearance rate (Ccr) and urea clearance rate (Curea), Kt/Vurea, and weekly Ccr were evaluated as parameters reflecting RRF. The serum CysC level was found to be negatively correlated with urine volume (r=-0.717, P<0.001), average of Ccr and Curea (r=-0.851, P<0.001), total and renal weekly Ccr (r=-0.795, P<0.001; r=-0.845, P<0.001, respectively), and renal Kt/Vurea (r=-0.793, P<0.001) and positively correlated with peritoneal weekly Ccr (r=0.738, P<0.001) and peritoneal Kt/Vurea (r=0.785, P<0.001). There was no significant association with total Kt/Vurea (r=-0.335, P=0.148). In non-anuric group of patients, serum CysC had no link to peritoneal Kt/Vurea (r=0.573, P=0.066), but was negatively correlated with renal Kt/Vurea (r=-0.609, P=0.047). In the multiple regression analysis, renal Kt/Vurea significantly contributed to log CysC concentration rather than peritoneal Kt/Vurea. The results of this study suggest that serum CysC could be an appropriate marker for RRF, independent of total and peritoneal Kt/Vurea.

Renal impairment caused by chronic occupational chromate exposure

To determine the nephritic toxicity of chromate after chronic occupational exposure. The environmental contamination was assessed by measuring the chromium (Cr) in 8-h airborne sampler. The integrated level of Cr was determined by Cr concentrations in the whole blood (WB-Cr) and the urine (U-Cr). The renal glomerular and tubule impairment was evaluated by determination of cystatin C (Cys-C) in the serum and microalbumin (mALB), urinary beta(2)-microglobulin (β(2)M), N-acetyl-beta-D-glucosaminidase (NAG) activity in the urine. The mean occupational exposure time to Cr was 12.86 years with average daily air level of 27.13 μg/m(3) comparing to 0.11 μg/m(3) of the background level. The WB-Cr and U-Cr were 23.49 μg/L and 17.41 μg/g creatinine (Cre), respectively in the chromate-exposed workers comparing to 3.32 μg/L and 1.52 μg/g Cre in the controls. The serum Cys-C and urinary mALB were significantly increased in the chromate-exposed workers. Exposure to Cr seems to induce an enhanced level of urinary NAG activity and β(2)M concentration. The increased serum Cys-C concentration was positively correlated with the level of serum Cre. The U-Cr was positively correlated to the concentrations of urinary mALB, β(2)M, and the activity of NAG. Chronic occupational exposure to chromate causes comprehensive renal impairment though more severity could occur in the tubule than in the glomerular.

Reference serum cystatin C levels in Japanese children

Single measurements of serum cystatin C (cysC) concentration have generally been used to determine glomerular filtration rate (GFR) in adults. Since GFR varies to some extent among children, we attempted to determine reference serum cysC concentrations for Japanese children. Serum cysC concentrations were determined by a latex particle-enhanced turbidimetric immunoassay in children who did not present with kidney disease or infectious disease, and the relationship between age and serum cysC level was assessed. We found that reference serum cysC levels gradually decreased during the first year after birth, thereafter becoming constant. Mean serum cysC concentration in children aged 1year (0.76±0.10mg/L) was slightly higher than in children aged ≥2years (0.70±0.09mg/L). Our reference values will be applicable for screening renal function in Japanese children.

Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥ 50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08-5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.

Evaluation of the Measurement of Serum Cystatin C by an Enzyme-Linked Immunosorbent Assay for Humans as a Marker of the Glomerular Filtration Rate in Dogs

The serum cystatin C (Cys-C) concentration is a better filtration marker than plasma creatinine (Cre) concentration in humans. In veterinary medicine, a few studies have shown that the serum Cys-C concentration in dogs is also a better marker than the plasma Cre concentration. The purpose of this study is to evaluate the applicability of measuring the serum Cys-C concentration by an enzyme-linked immunosorbent assay (ELISA) as a marker of the glomerular filtration rate in dogs with various renal dysfunctions. The serum Cys-C concentration in dogs with chronic kidney disease (CKD) was significantly higher (1.23 +/- 0.21 mg/L) than that in 76 control dogs (0.85 +/- 0.15) (P<0.001). The reference range of the serum Cys-C concentrations in samples from the 76 control dogs was 0.55-1.15 mg/l. Serum Cys-C concentration was more strongly correlated with plasma iohexol clearance (r=-0.704, P<0.001) than plasma Cre concentration in dogs (r=-0.598, P<0.001). In a receiver operating characteristics analysis, significant differences between the serum Cys-C and plasma Cre concentrations were found with regard to their AUC (0.949, [SE, 0.019] and 0.849 [SE, 0.029]) and diagnostic sensitivity (90.3% and 73.6%) for detecting decreased PCio (P<0.05). Therefore, the measurement of serum Cys-C concentration by ELISA is more useful for the detection of early CKD than measuring the plasma Cre concentration.

Cystatin C as a new biomarker of renal dysfunction in HIV-1 infected patients – preliminary report

HIV-1 infection and ARV therapy can cause progressive renal dysfunction. The aim of our study was to evaluate serum cystatine C (Cys-C) concentration and their possible relationships with the degree of renal injury in HIV-1 infected patients with or without antiretroviral therapy. Study was performed in 34 HIV(+) and 17 HIV(-) individuals. In 20 already treated HIV(+) Cys-C concentration was measured once; in the rest: before, after 3 and 9 months of HAART. Serum Cys-C concentration was measured by ELISA. Plasma urea and creatinine levels were measured. Creatine clearance was calculated by Cockroft-Gault formula. Serum Cys-C concentration in untreated and treated HIV(+) patients was significantly higher than in control group (441.94 ±121.62 and 513.10 ±94.12 v. 309.9 ±49.4 ng/ml, p < 0.001, respectively). After 3 months of HAART Cys-C concentration decreased to 379.74 ±42.15 ng/mL, and after 9 months increased to 384.52 ±41.23 ng/mL. Conclusion. Cys-C serum concentration is elevated in HIV-1-infected patients. Its decrease during the initial phase of ARV treatment suggests possible association with HIV viremia. HAART is associated with progressive increase of serum Cys-C concentration.

Cystatin C in cerebrospinal fluid and multiple sclerosis

A recent study using surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS). Surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects. Full-length CysC (13.4 kDa) concentration was similar in MS and control samples. The 12.5 kDa CysC protein was produced from full-length CysC by N-terminal cleavage during storage at -20 degrees C. The 12.5 kDa CysC isoform is a storage-related artifact and is not useful as a diagnostic marker for MS.

Urinary Cystatin C as a Marker of Tubular Dysfunction

Urinary Cystatin C as a Marker of Tubular DysfunctionCystatin C (CysC) is a nonglycosylated 13 KD protein that belongs to the type II cystatin gene family. It is a strong inhibitor of cysteine proteinases, freely filtered by the kidney glomerulus and reabsorbed by the tubulus, where it is almost totally catabolized. Remainder of the nonmetabolized CysC is eliminated in urine and may represent a useful marker of tubular dysfunction. The aim of the study was to confirm the clinical importance of the quantitative determination of CysC by an automated immunonephelometric method (DADE Behring). Two groups of patients were examined: one with glomerular (GD, n=36) and one with tubular dysfunction (TD, n=31), and compared with the control group (CG, n=31) of healthy males and females from laboratory personnel (n=11) and patients on routine systematic examination (n=20), from 25 to 58 years old. The patient groups were categorised according to the urine analysis of total proteins, creatinine and adequate proteins electrophoretic panel. CysC concentration in CG was in the range of 0.02-0.15 mg/L; 0.01-0.48 mg/L and 0.25-18 mg/L in GD and TD groups respectively. Values of means ± SD for patient groups (GD=0.11 ± 0.14; TD=3.92 ± 3.75 mg/L) showed statistical significance (p&lt;0.001) in the TD group in relation to GD and CG groups. It confirms that quantitative determination of CysC in one urine portion, with a fast laboratory method, might be a useful marker of tubular dysfunction, especially in emergency situations, taking into account that there is no interference of circadian variation on its concentration.

Serum Cistatin C in patients with delayed graft function

Despite recent studies showing that serum Cystatin C(CysC) is a better marker for glomerular filtration rate (GFR) than the ubiquitously used creatinine, the clinical utility of this remains to be evaluated. This marker is very sensitive for alograft function after renal transplantation. Concentration of CysC was compared with that of creatinine. Decreased renal function was followed in 64 transplanted patients. Plasma CysC significantly correlated (r=0.625, p&lt;0.001) with creatinine in healthy controls. In these patients the mean plasma creatinine and Cystatin C concentrations were: 81+/-13 mmol/L,0.90 +/-0.22 mg/L, respectively. Plasma Cystatin C and creatinine significantly correlated throughout the post-transplantation period (r=0.686, p&lt;0.001), but we confirmed differences between kinetics of these parameters. In the first four days after transplantation the CysC concentration was normalized faster than creatinine concentration. Development of acute rejection episode ( between 5 and 7 days) showed high sensitivity and specificity of the changes of CysC compared with those of creatinine.

Measurement of cystatin-C and creatinine in urine

Background: The concentration of serum cystatin-C (Cys-C) is highly correlated with creatinine (Cr), and is mainly determined by glomerular filtration; thus, Cys-C may be an index of the glomerular filtration rate (GFR). However, the kinetics of urinary Cys-C and Cr excretions are unclear. Thus, we investigated the kinetics of urinary Cys-C and Cr excretions, and examined whether the urinary Cys-C concentration can be used as a marker of renal function. Methods: The urinary excretion of Cys-C and Cr was evaluated in 1670 healthy subjects and 217 patients with proteinuria. We also investigated the urinary Cys-C concentration in 52 patients with chronic renal failure. Results: There was a good correlation between the urinary concentrations of Cys-C and Cr in the healthy group. This relation was also observed in patients showing persistent proteinuria without tubular cell damage. The mean urinary Cr concentration increased with age, and it was affected by the muscle mass. In contrast, the urinary Cys-C concentration was not affected by the muscle mass, and the concentration remained constant for all ages. We further found that the ratio of Cys-C to Cr (CCR) is a good index of the state of Cys-C reabsorption in the proximal tubules. Conclusions: The urinary CCR can be a marker of renal tubular dysfunction. In addition, when CCR was in the normal range, the urinary Cys-C concentration accurately reflected the glomerular filtration function.