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      Accuracy of cystatin C in prediction of acute kidney injury in children; serum or urine levels: which one works better? A systematic review and meta-analysis

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          Abstract

          Background

          There is still an ongoing discussion on the prognostic value of cystatin C in assessment of kidney function. Accordingly, the present study aimed to conduct a meta-analysis to provide evidence for the prognostic value of this biomarker for acute kidney injury (AKI) in children.

          Methods

          An extensive search was performed in electronic databases of Medline, Embase, ISI Web of Science, Cochrane library and Scopus until the end of 2015. Standardized mean difference (SMD) with a 95% of confidence interval (95% CI) and the prognostic performance characteristics of cystatin C in prediction of AKI were assessed. Analyses were stratified based on the sample in which the level of cystatin C was measured (serum vs. urine).

          Results

          A total of 24 articles were included in the meta-analysis [1948 children (1302 non-AKI children and 645 AKI cases)]. Serum (SMD = 0.96; 95% CI: 0.68-1.24; p < 0.0001) and urine (SMD = 0.54; 95% CI:0.34-0.75; p < 0.0001) levels of cystatin C were significantly higher in children with AKI. Overall area under the curve of serum cystatin C and urine cystatin C in prediction of AKI were 0.83 (95% CI: 0.80-0.86) and 0.85 (95% CI: 0.81-0.88), respectively. The best sensitivity (value = 0.85; 95% CI: 0.78-0.90) and specificity (value = 0.61; 95% CI: 0.48-0.73), were observed for the serum concentration of this protein and in the cut-off points between 0.4-1.0 mg/L.

          Conclusion

          The findings of the present study showed that cystatin C has an acceptable prognostic value for prediction of AKI in children. Since the serum level of cystatin C rises within the first 24 h of admission in patients with AKI, this biomarker can be a suitable alternative for traditional diagnostic measures.

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          Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

          Nagesh S Anavekar, John J V McMurray, Eric J Velazquez … (2004)
          The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction. Copyright 2004 Massachusetts Medical Society
          Article 0 comments Cited 374 times – based on 0 reviews     Review now
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            Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.

            Vikas R. Dharnidharka, Charles Kwon, Gary Stevens (2002)
            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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              Urinary biomarkers in the early diagnosis of acute kidney injury.

              W. Han, S. S. Waikar, A. Johnson … (2008)
              A change in the serum creatinine is not sensitive for an early diagnosis of acute kidney injury. We evaluated urinary levels of matrix metalloproteinase-9 (MMP-9), N-acetyl-beta-D-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) as biomarkers for the detection of acute kidney injury. Urine samples were collected from 44 patients with various acute and chronic kidney diseases, and from 30 normal subjects in a cross-sectional study. A case-control study of children undergoing cardio-pulmonary bypass surgery included urine specimens from each of 20 patients without and with acute kidney injury. Injury was defined as a greater than 50% increase in the serum creatinine within the first 48 h after surgery. The biomarkers were normalized to the urinary creatinine concentration at 12, 24, and 36 h after surgery with the areas under the receiver-operating characteristic curve compared for performance. In the cross-sectional study, the area under the curve for MMP-9 was least sensitive followed by KIM-1 and NAG. Combining all three biomarkers achieved a perfect score diagnosing acute kidney injury. In the case-control study, KIM-1 was better than NAG at all time points, but combining both was no better than KIM-1 alone. Urinary MMP-9 was not a sensitive marker in the case-control study. Our results suggest that urinary biomarkers allow diagnosis of acute kidney injury earlier than a rise in serum creatinine.
              Article 0 comments Cited 130 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Babak Nakhjavan-Shahraki: babak76003@yahoo.com
                Mahmoud Yousefifard: yousefifard20@gmail.com
                Neamatollah Ataei: ataei_nm@yahoo.com
                Masoud Baikpour: masoud_mbp@yahoo.com
                Fatemeh Ataei: mahmod_ano@yahoo.com
                Behnaz Bazargani: faster20@yahoo.com
                Arash Abbasi: arashabbasi875@gmail.com
                Parisa Ghelichkhani: ghelichkhani.parisa@gmail.com
                Faezeh Javidilarijani: p.pioneer24@yahoo.com
                Mostafa Hosseini: +982188989125 , mhossein110@yahoo.com
                Journal
                Journal ID (nlm-ta): BMC Nephrol
                Journal ID (iso-abbrev): BMC Nephrol
                Title: BMC Nephrology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2369
                Publication date (Electronic): 3 April 2017
                Publication date PMC-release: 3 April 2017
                Publication date Collection: 2017
                Volume: 18
                Electronic Location Identifier: 120
                Affiliations
                [1 ]GRID grid.411705.6, Pediatric Chronic Kidney Disease Research Center, Children’s Hospital Medical Center, , Tehran University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.411746.1, Physiology Research Center and Department of Physiology, Faculty of Medicine, , Iran University of Medical Sciences, ; Tehran, Iran
                [3 ]GRID grid.411705.6, Department of Pediatric Nephrology, Children’s Hospital Medical Center, , Tehran University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.411705.6, Department of Neurology, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                [5 ]GRID grid.411600.2, Department of Nuclear Medicine, Taleghani Hospital, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [6 ]GRID grid.411705.6, Department of Intensive Care Nursing, School of Nursing and Midwifery, , Tehran University of Medical Sciences, ; Tehran, Iran
                [7 ]Department of Pediatric Nephrology, Atieh Hospital, Tehran, Iran
                [8 ]GRID grid.411705.6, Department of Epidemiology and Biostatistics, School of Public Health, , Tehran University of Medical Sciences, ; Poursina Ave, Tehran, Iran
                Article
                Publisher ID: 539
                DOI: 10.1186/s12882-017-0539-0
                PMC ID: 5379579
                PubMed ID: 28372557
                SO-VID: 63113996-91fb-40ea-96b2-85e7228886c9
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 23 September 2016
                Date accepted : 24 March 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004484, Tehran University of Medical Sciences and Health Services;
                Award ID: 94-02-184-28895
                Award Recipient :
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Nephrology
                Keywords: cystatin c,acute kidney injury,prognostic value
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: cystatin c, acute kidney injury, prognostic value

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