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      Serum Cystatin C as a Marker of Renal Function in Critically Ill Patients With Normal Serum Creatinine

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          Abstract

          Background:

          Serum creatinine as a classic marker of renal function has several limitations in the detection of renal dysfunction.

          Objectives:

          This study assessed the validity of serum cystatin C as a marker of renal function in critically ill patients with normal serum creatinine.

          Patients and Methods:

          Eighty adult patients referred to intensive care units with serum creatinine levels < 1.5 mg/dL and without hemodynamic instability were chosen and their serum creatinine and cystatin C levels were measured. A 24-hour urine sample was collected to calculate creatinine clearance (Ccr). Renal dysfunction was defined as Ccr < 80 mL/min/1.73 m 2.

          Results:

          There were significant correlations between measured Ccr and 1/serum creatinine (R = 0.51, P < 0.001) and 1/serum cystatin C (R = 0.25, P = 0.028). The difference between false negative rates of serum creatinine (93.33%) and cystatin C (80%) in the detection of renal dysfunction was significant (P = 0.032). Receiver operating characteristic curve analysis illustrated that area under the curve of serum creatinine and cystatin C for detecting renal dysfunction were 0.711 and 0.607, respectively; however, this difference was not significant (P = 0.222).

          Conclusions:

          Our data demonstrated that serum cystatin C is not superior to serum creatinine in the early detection of renal dysfunction in critically ill patients.

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          Most cited references43

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          Prediction of creatinine clearance from serum creatinine.

          A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.

            Serum cystatin C (Cys C) has been proposed as a simple, accurate, and rapid endogenous marker of glomerular filtration rate (GFR) in research and clinical practice. However, there are conflicting reports regarding the superiority of Cys C over serum creatinine (Cr), with a few studies suggesting no significant difference. We performed a meta-analysis of available data from various studies to compare the accuracy of Cys C and Cr in relation to a reference standard of GFR. A bibliographic search showed 46 articles until December 31, 2001. We also retrieved data from eight other studies presented and published in abstract form. The overall correlation coefficient for the reciprocal of serum Cys C (r = 0.816; 95% confidence interval [CI], 0.804 to 0.826) was superior to that of the reciprocal of serum Cr (r = 0.742; 95% CI, 0.726 to 0.758; P < 0.001). Similarly, receiver operating characteristic (ROC)-plot area under the curve (AUC) values for 1/Cys C had greater identity with the reference test for GFR (mean ROC-plot AUC for Cys C, 0.926; 95% CI, 0.892 to 0.960) than ROC-plot AUC values for 1/Cr (mean ROC-plot AUC for serum Cr, 0.837; 95% CI, 0.796 to 0.878; P < 0.001). Immunonephelometric methods of Cys C assay produced significantly greater correlations than other assay methods (r = 0.846 versus r = 0.784; P < 0.001). In this meta-analysis using currently available data, serum Cys C is clearly superior to serum Cr as a marker of GFR measured by correlation or mean ROC-plot AUC. Copyright 2002 by the National Kidney Foundation, Inc.
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              Early detection of acute renal failure by serum cystatin C.

              Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/=50% (R-criteria), by >/=100% (I-criteria), or by >/=200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/=50%, by >/=100%, or by >/=200%. Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/=50% 1.5 +/- 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.
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                Author and article information

                Journal
                Nephrourol Mon
                Nephrourol Mon
                10.5812/numonthly
                Kowsar
                Nephro-urology Monthly
                Kowsar
                2251-7006
                2251-7014
                01 March 2014
                March 2014
                : 6
                : 2
                : e15224
                Affiliations
                [1 ]Nephrology Urology Research Center and Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
                [2 ]Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IR Iran
                [3 ]Transplant Research Center and Department of Pathology, Shiraz University of Medical Sciences, Shiraz, IR Iran
                [4 ]Department of Dermatology, Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaz, IR Iran
                [5 ]Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran
                Author notes
                [* ]Corresponding author: Iman Karimzadeh, Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2166954709, E-mail: karimzadehiman@ 123456yahoo.com
                Article
                10.5812/numonthly.15224
                3997954
                24783172
                a911829f-0822-4b11-bddb-d195c1a9ff12
                Copyright © 2014, Nephrology and Urology Research Center; Published by Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 October 2013
                : 24 October 2013
                : 07 December 2013
                Categories
                Research Article

                critically ill,patients,creatinine,cystatin c,acute kidney injury

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