Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-beta(1). The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.
J Clin Invest 1999 Nov
PMID:Cystatin C deficiency in human atherosclerosis and aortic aneurysms. 1054 13

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 mumol/L, 58-120 ml/min/1.73 m2 and 0.51-0.98 mg/L, respectively. For women, the intervals were 68-98 mumol/L, 60-119 ml/min/1.73 m2 and 0.49-0.94 mg/L; for men, they were 78-123 mumol/L, 57-122 ml/min/1.73 m2 and 0.56-0.98 mg/L. This mean 95% reference interval for cystatin C in all donors under 50 years of age was 0.53-0.92 mg/L; for those over 50 years of age it was 0.58-1.02 mg/L. The small difference between make and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.
Ann Clin Biochem 2000 Jan
PMID:Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance. 1067 73

The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.
Clin Cancer Res 2000 Feb
PMID:Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. 1069 May 31

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.
Scand J Clin Lab Invest 1999 Dec
PMID:Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults. 1069 Oct 49

We report a new case of giant cell angiitis of the central nervous system associated with cerebral amyloid angiopathy (GA/CAA). A 67-year-old woman was hospitalized with a history of headaches and lapses of consciousness. After improvement with corticosteroidtherpay, treatment was stopped. She relapsed and died 33 days after first admission. Pathological examination showed unusual extension of GA/CAA lesions, in the superficial and deep layer of the cerebral cortex, and in the cerebellum. Simultaneous occurrence of GA and CAA is rare. Histopathologic findings and immunological pathogenesis of the process are discussed: 1) arguments over pre-existence of CAA, responsible for GA; 2) primitive inflammatory process inducing amyloid deposits; 3) GA/CAA may represent an association of histological lesions related to 2 different types of disease: i) neurodegenerative disease with specific lesions (such as presence of diffuse senile plaques and neurofibrillary tangles) inducing inflammatory reaction ii) inflammatory disease, with few or no degenerative lesions, responding to immunotherapy.
Clin Exp Pathol 1999
PMID:Giant cell angiitis of the central nervous system with amyloid angiopathy. A case report and review of the literature. 1081 37

The assessment of the glomerular filtration rate (GFR) is the most commonly used test of renal function. The accepted reference procedure employs an exogenous clearance marker whilst the most popular test is that of serum or plasma creatinine. All of these tests have limitations, although the surrogate endogenous markers are the most practical. Cystatin C, a low molecular weight protein which can be measured by light scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Data on reference ranges indicate that circulating cystatin C levels reflect the variation in GFR throughout life and the marker demonstrates a better correlation with the reference procedure than serum creatinine.
Clin Chim Acta 2000 Jul
PMID:Developments in the assessment of glomerular filtration rate. 1084 8

It has been reported that cystatin C (cys-C) is elevated in patients with malignant disease. In order to investigate whether this phenomenon is linked to or independent of renal function, and at the same time examine the role of this marker in other pathological situations, cys-C concentrations were compared with 24-h creatinine clearance values in three groups of patients; the first group were undergoing treatment for malignant disease, the second group were renal transplant patients and the third randomly taken from patients for whom a routine creatinine clearance had been requested. Several patients with malignant disease had high cys-C levels without any correspondence to creatinine clearance values. Additionally, although cys-C shows a high sensitivity for detecting impaired glomerular function in renal transplant patients, the specificity was very low, with little discrimination being observed between patients with normal and pathological creatinine clearance levels. In other patients both the sensitivity and specificity of cys-C could be shown to be very good. Thus although cys-C can generally be recommended as a marker of the glomerular filtration rate, there are some patients for whom the clinical relevance is unclear.
Clin Chim Acta 2000 Jul
PMID:Clinical value of cystatin C determination. 1084 9

In the last years the search for sensitive and specific markers of renal damage and/or renal function has conducted to the development of laboratory assays for measurement of urinary proteins such as albumin, beta(2)-microglobulin, alpha(1)-microglobulin, cystatin C, etc. Furthermore, there have been new applications of already known markers based on different, reformulated methods which often rely on more advanced technologies. It is evident that such developments are connected with analytical and interpretative problems for laboratory managers and clinicians. In this situation, it is essential that international societies develop comprehensive measures for the quality management of these assays and issue uniform and carefully elaborated guidelines to ensure optimal test utilization. International activities are also directed to the development of optimized and standardized methods as well as to the production and evaluation of appropriate reference materials and, finally, to the establishment of appropriate reference ranges and cut-off values for specific analytes. The main use of reference materials is in the transfer of their accurately assigned values to the calibrators of diagnostic companies for calibration of commercially available test systems. These international standardization activities and strategies will allow a harmonized approach to disease management using a more reliable laboratory testing based on quality and value.
Clin Chim Acta 2000 Jul
PMID:Standardization activities for harmonization of test results. 1084 25

The effect of asthma pathogenesis on serum cystatin C, a potent inhibitor of cysteine proteinases and a newly proposed marker of the renal function, has not been yet determined. The objectives were to determine the 24-h pattern of cystatin C and creatinine concentrations in sera of asthmatic patients in order to test whether their concentrations might reflect circadian rhythms, the disease severity and the effect of therapy. Serum concentrations of cystatin C and creatinine were determined in steroid-independent and steroid-dependent asthmatics before and after 1 week of treatment with methylprednisolone and cyclosporin A, respectively. Samples were collected every 4 h during a 24-h period. Little or no significant effects of time on cystatin C and creatinine concentrations over a 24-h period were observed in healthy and asthmatic sera. However, significantly higher cystatin C concentrations were found in asthmatic patients compared to controls which suggests its role in the pathogenesis of asthma. Methylprednisolone increased and cyclosporin A decreased serum cystatin C concentrations after 1 week of therapy. Additionally these results support the need for the evaluation of cystatin C as a marker of glomerular filtration rate determination in asthma.
Clin Chim Acta 2000 Oct
PMID:Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. 1095 65

Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5 years, and treated with NSAIDs for more than 50 months, were included in the study. Besides conventional markers of renal function (i.e. plasma creatinine, estimated glomerular filtration rate, creatinine clearance), we analysed plasma cystatin C by an automated, nephelometric immunoassay on a Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels of plasma cystatin C, whereas only three out of 56 patients showed an elevated plasma creatinine, even though the creatinine clearance was decreased in 57% of these patients. Cystatin C exhibited a by far better correlation with creatinine clearance than plasma creatinine. In conclusion, patients with prolonged RA for more than 50 months, show a disturbed renal function despite normal plasma creatinine. Elevated cystatin C indicates such incipient renal disease, and is, not least because of a simple, well reproducible technique, more recommendable for screening purposes than tedious clearance determinations.
Clin Chim Acta 2000 Oct
PMID:Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis. 1095 75


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