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Accuracy of Urine Kidney Injury Molecule-1 in Predicting Acute Kidney Injury in Children; a Systematic Review and Meta-Analysis

Mojtaba Fazel, Arash Sarveazad, Kosar Mohamed Ali, Mahmoud Yousefifard, Mostafa Hosseini



Introduction: There is considerable controversy on the accuracy of Kidney Injury Molecule-1 (KIM-1) in prediction of acute kidney injury (AKI) in children. Therefore, the present study intends to provide a systematic review and meta-analysis of the value of this biomarker in predicting AKI in children.

Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of 2019. Cohort and case-control studies on children were included. Urinary KIM-1 levels were compared between AKI and non-AKI groups. Findings were reported as an overall standardized mean difference (SMD) with a 95% confidence interval (CI). Also, the overall area under the receiver operating characteristic (ROC) curve (AUC) of KIM-1 in predicting AKI in children was calculated.

Results: Data from 13 articles were included. Urinary KIM-1 levels in children with stage 1 AKI were higher than the non-AKI group only when assessed within the first 12 hours after admission (SMD = 0.95; 95% CI: 0.07 to 1.84; p = 0.034). However, urinary KIM-1 levels in children with stage 2-3 AKI were significantly higher than non-AKI children (p <0.01) at all times. The AUC of urinary KIM-1 in predicting AKI in children was 0.69 (95% CI: 0.62 to 0.77).

Conclusion: Based on the available evidence, KIM-1 seems to have moderate value in predicting AKI in children. Since previous meta-analyses have provided other urinary and serum biomarkers that have better discriminatory accuracy than KIM-1, so it had better not to use KIM-1 in predicting AKI in children.


Acute Kidney Injury; Renal Insufficiency; HAVCR1 protein, human; Hepatitis A Virus Cellular Receptor 1


Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038-47.

Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau J-L, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285-95.

Devarajan P. Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr. 2011;23(2):194.

Nakhjavan-Shahraki B, Yousefifard M, Ataei N, Baikpour M, Ataei F, Bazargani B, et al. 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. BMC Nephrol. 2017;18(1):120.

Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Ataei N, et al. Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury; a systematic review and meta-analysis. Int J Pediatr. 2016;4(11):3815-36.

Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Hosseini M. Diagnostic value of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) in detection of pediatric acute kidney injury; a systematic review and meta-analysis. Int J Pediatr. 2016;4(11):3875-95.

Mitsnefes MM, Kathman TS, Mishra J, Kartal J, Khoury PR, Nickolas TL, et al. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2007;22(1):101-8.

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. The Lancet. 2005;365(9466):1231-8.

Nickolas TL, Barasch J, Devarajan P. Biomarkers in acute and chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17(2):127-32.

Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62(1):237-44.

Waanders F, van Timmeren MM, Stegeman CA, Bakker SJ, van Goor H. Kidney injury molecule-1 in renal disease. J Pathol. 2010;220(1):7-16.

Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, et al. Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol. 2014;25(10):2177-86.

Ucakturk A, Avci B, Genc G, Ozkaya O, Aydin M. Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children. J Pediatr Endocrinol Metab. 2016;29(2):145-51.

Shao X, Tian L, Xu W, Zhang Z, Wang C, Qi C, et al. Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis. PLoS One. 2014;9(1):e84131.

Wang H, Wang WJ, Zhou CC, Cen D. Accuracy of urinary kidney injury molecule-1 in predicting acute kidney injuries associated with cardiac surgery: a systematic review and meta-analysis. Int J Clin Exp Med. 2019;12(6):6570-8.

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology. JAMA: the journal of the American Medical Association. 2000;283(15):2008-12.

Yousefifard M, Baikpour M, Ghelichkhani P, Asady H, Darafarin A, Esfahani MRA, et al. Comparison of Ultrasonography and Radiography in Detection of Thoracic Bone Fractures; a Systematic Review and Meta-Analysis. Emergency. 2016;4(2):55.

Yousefifard M, Baikpour M, Ghelichkhani P, Asady H, Nia KS, Jafari AM, et al. Screening Performance Characteristic of Ultrasonography and Radiography in Detection of Pleural Effusion; a Meta-Analysis. Emergency. 2016;4(1):1.

Ebrahimi A, Yousefifard M, Kazemi HM, Rasouli HR, Asady H, Jafari AM, et al. Diagnostic accuracy of chest ultrasonography versus chest radiography for identification of pneumothorax: a systematic review and meta-analysis. Tanaffos. 2014;13(4):29-40.

Hosseini M, Yousefifard M, Aziznejad H, Nasirinezhad F. The Effect of Bone Marrow–Derived Mesenchymal Stem Cell Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta-Analysis. Biol Blood Marrow Transplant. 2015;21(9):1537-44.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9.

Whiting PF, Rutjes AWS, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Ann Intern Med. 2011;155(8):529-36.

Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2011.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34.

Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, et al. Urine biomarkers predict acute kidney injury in newborns. J Pediatr. 2012;161(2):270-5.e1.

Carvalho Pedrosa D, Macedo de Oliveira Neves F, Cavalcante Meneses G, Pinheiro Gomes Wirtzbiki G, da Costa Moraes CA, Costa Martins AM, et al. Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study. Pediatr Nephrol. 2015;30(12):2207-13.

Dong L, Ma Q, Bennett M, Devarajan P. Urinary biomarkers of cell cycle arrest are delayed predictors of acute kidney injury after pediatric cardiopulmonary bypass. Pediatr Nephrol. 2017;32(12):2351-60.

Du Y, Zappitelli M, Mian A, Bennett M, Ma Q, Devarajan P, et al. Urinary biomarkers to detect acute kidney injury in the pediatric emergency center. Pediatr Nephrol. 2011;26(2):267-74.

Gist KM, Goldstein SL, Wrona J, Alten JA, Basu RK, Cooper DS, et al. Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatr Nephrol. 2017;32(9):1611-9.

Kandur Y, Gonen S, Fidan K, Soylemezoglu O. Evaluation of urinary KIM-1, NGAL, and IL-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi. Clin Nephrol. 2016;86(2):62-9.

Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301-9.

Lagos-Arevalo P, Palijan A, Vertullo L, Devarajan P, Bennett MR, Sabbisetti V, et al. Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine? Pediatr Nephrol. 2015;30(4):665-76.

McCaffrey J, Coupes B, Chaloner C, Webb NJ, Barber R, Lennon R. Towards a biomarker panel for the assessment of AKI in children receiving intensive care. Pediatr Nephrol. 2015;30(10):1861-71.

Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL, et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol. 2013;8(7):1079-88.

Peco-Antic A, Ivanisevic I, Vulicevic I, Kotur-Stevuljevic J, Ilic S, Ivanisevic J, et al. Biomarkers of acute kidney injury in pediatric cardiac surgery. Clin Biochem. 2013;46(13-14):1244-51.

Sarafidis K, Tsepkentzi E, Agakidou E, Diamanti E, Taparkou A, Soubasi V, et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol. 2012;27(9):1575-82.

Westhoff JH, Fichtner A, Waldherr S, Pagonas N, Seibert FS, Babel N, et al. Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury. Pediatr Nephrol. 2016;31(12):2353-63.

DOI: https://doi.org/10.22037/aaem.v8i1.584

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