Cystatin C in Prediction of Acute Kidney Injury: A Systemic Review and Meta-analysis

Background: Cystatin C (CysC) has been proposed as a filtration marker for the early detection of acute kidney injury (AKI); however, a wide range of its predictive accuracy has been reported. Study Design: Meta-analysis of diagnostic test studies. Setting & Population: Various clinical settings of AKI, including patients after cardiac surgery, pediatric patients, and critically ill patients. Selection Criteria: Computerized search of PubMed, Current Contents, CINAHL, and EMBASE from inception until November 15, 2010, was performed to identify potentially relevant articles. Inclusion criteria were studies investigating the diagnostic accuracy of CysC level to predict AKI. There were no language restrictions in the search. Index Tests: Increasing or increased serum CysC level or urinary CysC excretion. Reference Tests: The outcome was the development of AKI, primarily based on serum creatinine level (definition varied across studies). Results: We analyzed data from 19 studies and 11 countries involving 3,336 patients. Of these studies, 13 could be included in the meta-analysis. Across all settings, the diagnostic OR for serum CysC level to predict AKI was 23.5 (95% CI, 14.2-38.9), with sensitivity and specificity of 0.84 and 0.82, respectively. The area under the receiver operating characteristic curve (AUROC) of serum CysC level to predict AKI was 0.96 (95% CI, 0.95-0.97). Subgroup analysis showed that serum CysC was of diagnostic value when measured early (within 24 hours after renal insult or intensive care unit admission). For the diagnostic value of urinary CysC excretion, the diagnostic OR was 2.60 (95% CI, 2.01-3.35), with sensitivity and specificity of 0.52 and 0.70, respectively. The AUROC of urinary CysC excretion to predict AKI was 0.64 (95% CI, 0.62-0.66). Limitations: Variation in criteria for definitions of index and reference tests, absence of measured glomerular filtration rate in most studies. Conclusion: Serum CysC appears to be a good biomarker in the prediction of AKI, whereas urinary CysC excretion has only moderate diagnostic value. Am J Kidney Dis. 58(3): 356-365. (C) 2011 by the National Kidney Foundation, Inc.