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      Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction

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          Abstract

          Background

          Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C might also be a more sensitive marker of acute renal dysfunction. This study aims to compare cystatin C and creatinine for detection of acute allograft dysfunction in children using pediatric RIFLE (risk of renal dysfunction, injury to the kidney, failure or loss of kidney function, end stage renal disease) criteria for acute kidney injury.

          Methods

          Retrospective chart review of post-transplant period in 24 patients in whom creatinine and cystatin C were measured every day. Allograft dysfunction was defined as a sustained rise in marker concentration above the mean of the three preceding measurements.

          Results

          In total, there were 13 episodes of allograft dysfunction. Maximum RIFLE stages with creatinine were 'R' in 7, 'I' in 4, and 'F' in 2, with cystatin C ‘R’ in 6, ‘I’ in 4 and ‘F’ in 3, respectively. In 9/13 cases, both markers rose simultaneously, in three, the rise in creatinine preceded cystatin C by 1–5 days (median 4). In one case, the rise in cystatin C preceded creatinine by 1 day. The time lag was not statistically different. The maximum relative rise of creatinine was significantly higher than cystatin C. By multiple linear regression analysis, the maximum rise of cystatin C was related to the maximum rise of creatinine, but independent of patient age, gender, steroid dose, and anthropometric data.

          Conclusions

          In this pediatric population, cystatin C was not superior to creatinine for the detection of acute allograft dysfunction.

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          Most cited references27

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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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            Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children--a meta-analysis.

            To perform a systematic review comparing the diagnostic accuracy of CysC with SCr. MEDLINE and EMBASE (January 1984-February 2006) were searched. Studies included i) evaluated CysC against a recognised 'gold standard' method for determining GFR using a receiver operating characteristics (ROC) curve analysis and ii) included data that could be extracted into a 2x2 table. The search identified 27 population groups in 24 studies (n=2007) that compared the diagnostic accuracy of CysC with SCr. The diagnostic odds ratios (DORs) (95% CI) of predicting renal dysfunction derived from a Moses-Littenberg linear regression model were 3.99 (3.41-4.57) for CysC and 2.79 (2.12-3.46) for SCr. The diagnostic accuracy for impaired renal function favours CysC. However, the confidence intervals for the pooled DORs for the biomarkers overlap. The ability of CysC (cut-off values between 0.9 and 1.4 mg/L) to rule in renal impairment (as measured by inulin-determined GFR of 60-79 mL/min/1.73 m2) in persons in whom this is suspected is large and conclusive.
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              Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study.

              To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Single-center, prospective observational study. Tertiary hospital. One hundred adult cardiac surgical patients. We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point. Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.
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                Author and article information

                Contributors
                +31-204-444444 , +31-204-440849 , a.bokenkamp@vumc.nl
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer-Verlag (Berlin/Heidelberg )
                0931-041X
                1432-198X
                30 December 2011
                30 December 2011
                May 2012
                : 27
                : 5
                : 843-849
                Affiliations
                [1 ]Department of Pediatric Nephrology, VU University Medical Center, Postbox 7057, 1007 MB Amsterdam, The Netherlands
                [2 ]Pediatric Nephrology, Hannover Medical School, Hannover, Germany
                [3 ]Pediatric Nephrology, Academic Medical Center, Amsterdam, The Netherlands
                [4 ]Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands
                Article
                2073
                10.1007/s00467-011-2073-9
                3315636
                22207347
                937f05b0-7ee0-41a7-afe6-a20b5f2d600b
                © The Author(s) 2011
                History
                : 20 July 2011
                : 14 November 2011
                : 17 November 2011
                Categories
                Original Article
                Custom metadata
                © IPNA 2012

                Nephrology
                pharmacokinetic modeling,serum cystatin c,allograft dysfunction,acute renal failure,children,kidney transplantation,serum creatinine

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