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      Serum Cystatin C Reliably Detects Renal Dysfunction in Patients with Various Renal Diseases

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          A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h C<sub>Cr</sub>) and the standard sodium thiosulfate clearance test (C<sub>Thio</sub>) within a week of blood sample collection. Serum cystatin C concentration was determined by a particle-enhanced immunonephelometry method. C<sub>Thio</sub> and 1/cystatin C, 24 h C<sub>Cr</sub>, 1/β<sub>2</sub>-microglobulin and 1/creatinine were well correlated. The correlation coefficients for C<sub>Thio</sub> obtained by 24 h C<sub>Cr</sub> and 1/cystatin C were comparable to each other (0.701 vs. 0.679). Receiver-operated characteristic (ROC) analysis revealed that 24 h C<sub>Cr</sub> showed the highest area under the curve when C<sub>Thio</sub> = 60 ml/min or C<sub>Thio</sub> = 100 ml/min were applied as the discrimination point. However, the ROC value obtained by cystatin C was slightly greater than 24 h C<sub>Cr</sub> when C<sub>Thio</sub> = 80 ml/min was used as the discrimination point. Patient age, gender, glucose tolerance, presence of proteinuria, systemic inflammation, lupus, or systemic use of steroids did not interfere in the relationship between C<sub>Thio</sub> and 1/cystatin C. In conclusion, serum cystatin C measurement is an excellent diagnostic test for detecting patients with subclinical renal dysfunction.

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          Most cited references 6

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          The cystatins: protein inhibitors of cysteine proteinases.

          The last decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stefins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors.
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            Evaluation of the Dade Behring N Latex Cystatin C assay on the Dade Behring Nephelometer II System.

            The Dade Behring N Latex Cystatin C assay, a particle-enhanced nephelometric immunoassay for measuring serum cystatin C, was evaluated on the Dade Behring Nephelometer II. The assay time was 6 min and the throughput was 75 samples per hour. The sample volume was 40 microL and the measuring range was 0.25-7.90 mg/L. Imprecision studies revealed within-run CVs < 1.8% and between-run CVs < 1.8% in the concentration range 0.87-4.63 mg/L. Recovery was 92.4-101.3%. Linearity studies showed excellent correlation between the theoretical and obtained values. No interferences were detected from haemoglobin < 1.0 mmol/ L, bilirubin <512 micromol/L and Intralipid <20 g/L. Stability of cystatin C in serum was 7 days at temperatures from 20 degrees C to 20 degrees C and 6 months at -80 degrees C. Measurements of cystatin C in heparin-plasma and EDTA-plasma did not differ significantly from cystatin C measured in serum. Fifty patient samples run on the Dade Behring Nephelometer II (y) were compared to the Dako Cystatin C assay (x). The Passing-Bablok regression analysis revealed y = 1.105x - 0.340. In conclusion, the Dade Behring N Latex Cystatin C assay was precise and correlated with the Dako Cystatin C assay.
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              How to assess glomerular function and damage in humans.

              In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations. Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass. Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration-time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration-time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently, 125l-iothalamate, 99mTc-diethylenethiaminepenta-acetic acid and 51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR. In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance. Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

                Author and article information

                S. Karger AG
                May 2002
                02 May 2002
                : 91
                : 1
                : 13-20
                Department of Medicine (II), Niigata University Medical School, Niigata, Japan
                57599 Nephron 2002;91:13–20
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 3, References: 29, Pages: 8
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/57599
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