Abstract
Multiple urinary biomarkers have been reported in differentiation of nonobstructive dilatation (NOD) from ureteropelvic junction obstruction (UPJO). In this meta-analysis, we compared the accuracy of common urinary biomarkers applicable to UPJO. A systematic literature review of electronic databases was conducted for: (UPJO) OR (NOD) AND (urinary biomarkers) AND (children) for articles published in the last decade. PRISMA guidelines were used to exclude duplicate and erroneous articles. Meta-analysis involved risk of bias analysis, heterogeneity assessment, and comparison of sensitivity/specificity by forest plot analysis using MetaXL 5.3. Among the 264 articles analyzed, 19 articles met the inclusion criteria and reported the following: neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1 (MCP1), carbohydrate antigen 19–9 (CA 19–9), kidney injury molecule (KIM1), epidermal growth factor (EGF), and interferon gamma induced protein-10 (IP10). There was substantial heterogeneity among articles. There was wide variation in applied cut-offs among studies. Overall sensitivity was highest at 87% for CA 19–9 while overall specificity was highest at 76% for NGAL. Overall accuracy was highest at 78% for CA 19–9 followed by 77% for NGAL and 75% for KIM1. In this meta-analysis, the overall accuracy was highest for CA 19–9 followed by NGAL and KIM1. The small number of studies for CA 19–9 and considerable heterogeneity for all should be considered while interpreting these findings. Based on the current meta-analysis, we support a panel of biomarkers combining NGAL, KIM, and CA 19–9 for the best diagnostic accuracy of UPJO in children.
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References
Cheng H-L (2014) Surgical indications for unilateral neonatal hydronephrosis in considering ureteropelvic junction obstruction. Urol Sci 25:73–76. https://doi.org/10.1016/j.urols.2012.05.002
Passoni NM, Peters CA (2020) Managing ureteropelvic junction obstruction in the young infant. Front Pediatr 8:242. https://doi.org/10.3389/fped.2020.00242
Babu R, Ninan B, Sai V (2018) Evaluating neonates with antenatal hyderonephrosis using a standard protocol: an audit of hospital records. Indian Pediatr 55:966–968. https://doi.org/10.1007/s13312-018-1419-9
Babu R, Venkatachalapathy E, Sai V (2019) Hydronephrosis severity score: an objective assessment of hydronephrosis severity in children—a preliminary report. J Pediatr Urol 15:68.e1-68.e6. https://doi.org/10.1016/j.jpurol.2018.09.020
Lucarelli G, Mancini V, Galleggiante V, Rutigliano M, Vavallo A, Battaglia M, Ditonno P (2014) Emerging urinary markers of renal injury in obstructive nephropathy. Biomed Res Int 2014:303298. https://doi.org/10.1155/2014/303298
Jackson L, Woodward M, Coward RJ (2018) The molecular biology of pelvi-ureteric junction obstruction. Pediatr Nephrol 33:553–571. https://doi.org/10.1007/s00467-017-3629-0
Washino S, Hosohata K, Miyagawa T (2020) Roles played by biomarkers of kidney injury in patients with upper urinary tract obstruction. Int J Mol Sci 21:5490. https://doi.org/10.3390/ijms21155490
Paraboschi I, Mantica G, Dalton NR, Turner C, Garriboli M (2020) Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review. Transl Androl Urol 9:722–742. https://doi.org/10.21037/tau.2020.01.01
Papachristou F, Pavlaki A, Printza N (2014) Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review. Biomarkers 19:531–540. https://doi.org/10.3109/1354750X.2014.943292
Bartoli F, Penza R, Aceto G, Niglio F, D’Addato O, Pastore V, Campanella V, Magaldi S, Lasalandra C, Di Bitonto G, Gesualdo L (2011) Urinary epidermal growth factor, monocyte chemotactic protein-1, and β2-microglobulin in children with ureteropelvic junction obstruction. J Pediatr Surg 46:530–536. https://doi.org/10.1016/j.jpedsurg.2010.07.057
Grandaliano G, Gesualdo L, Bartoli F, Ranieri E, Monno R, Leggio A, Paradies G, Caldarulo E, Infante B, Schena FP (2000) MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy. Kidney Int 58:182–192. https://doi.org/10.1046/j.1523-1755.2000.00153.x
Pavlaki A, Printza N, Farmaki E, Stabouli S, Taparkou A, Sterpi M, Dotis J, Papachristou F (2020) The role of urinary NGAL and serum cystatin C in assessing the severity of ureteropelvic junction obstruction in infants. Pediatr Nephrol 35:163–170. https://doi.org/10.1007/s00467-019-04349-w
Alizadeh F, Taefnia AM, Haghdani S (2018) Urinary carbohydrate antigen 19–9/creatinine ratio: a non-invasive marker for follow-up of unilateral ureteropelvic junction obstruction in children. J Pediatr Urol 14:62.e1-62.e4. https://doi.org/10.1016/j.jpurol.2017.09.012
Keshri R, Govindarajan KK, Rajappa M, Sambandan K, Naredi BK, Jindal B (2021) Can urinary biomarkers be used in the outcome assessment of pyeloplasty in children? Afr J Urol 27:115. https://doi.org/10.1186/s12301-021-00217-y
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700–b2700. https://doi.org/10.1136/bmj.b2700
McGuinness LA, Higgins JPT (2021) Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Syn Methods 12:55–61. https://doi.org/10.1002/jrsm.1411
Amiri R, Hosseini H, Sanaei Z, Shamahmoudi S, Solgi G (2021) Urinary neutrophil glatinase-associated lipocalin level (uNGAL) may predict the severity of congenital hydronephrosis in infants. Am J Clin Exp Immunol 10:1–7
Yücel ÖB, Dönmez Mİ, Küçükgergin C, Ziylan O, Seçkin Ş, Oktar T (2021) Urinary biomarkers can identify the need for pyeloplasty in presence of supranormal differential renal function in antenatally diagnosed unilateral hydronephrosis. J Pediatr Urol. https://doi.org/10.1016/j.jpurol.2021.08.015
Wasilewska A, Taranta-Janusz K, Dębek W, Zoch-Zwierz W, Kuroczycka-Saniutycz E (2011) KIM-1 and NGAL: new markers of obstructive nephropathy. Pediatr Nephrol 26:579–586. https://doi.org/10.1007/s00467-011-1773-5
Mohammadjafari H, Rafiei A, Mousavi SA, Alaee A, Yeganeh Y (2014) Role of urinary levels of endothelin-1, monocyte chemotactic peptide-1, and N-acetyl glucosaminidase in predicting the severity of obstruction in hydronephrotic neonates. Korean J Urol 55:670. https://doi.org/10.4111/kju.2014.55.10.670
Madsen MG, Nørregaard R, Palmfeldt J, Olsen LH, Frøkiær J, Jørgensen TM (2013) Epidermal growth factor and monocyte chemotactic peptide-1: potential biomarkers of urinary tract obstruction in children with hydronephrosis. J Pediatr Urol 9:838–845. https://doi.org/10.1016/j.jpurol.2012.11.011
Taranta-Janusz K, Wasilewska A, Dębek W, Waszkiewicz-Stojda M (2012) Urinary cytokine profiles in unilateral congenital hydronephrosis. Pediatr Nephrol 27:2107–2113. https://doi.org/10.1007/s00467-012-2230-9
Nabavizadeh B, Khorramirouz R, Amini E, Pishgar F, Hojjat A, Kajbafzadeh AM (2019) Value of urinary carbohydrate antigen 19–9 to predict failure of conservative management in children with ureteropelvic junction obstruction. J Pediatr Surg 54:1650–1653. https://doi.org/10.1016/j.jpedsurg.2018.09.007
Atar A, Oktar T, Kucukgergin C, Kalelioglu I, Seckin S, Ander H, Ziylan O, Kadioglu TC (2015) The roles of serum and urinary carbohydrate antigen 19–9 in the management of patients with antenatal hydronephrosis. J Pediatr Urol 11:133.e1-133.e5. https://doi.org/10.1016/j.jpurol.2014.12.012
Kajbafzadeh A-M, Elmi A, Talab SS, Emami H, Esfahani SA, Saeedi P (2010) Urinary and Serum carbohydrate antigen 19–9 as a biomarker in ureteropelvic junction obstruction in children. J Urol 183:2353–2360. https://doi.org/10.1016/j.juro.2010.02.031
Mohammadjafari H, Rafiei A, Kosaryan M, Yeganeh Y, Hosseinimehr SJ (2014) Determination of the severity of ureteropelvic junction obstruction using urinary epidermal growth factor and kidney injury molecule 1 levels. Biomark Med 8:1199–1206. https://doi.org/10.2217/bmm.14.79
Li Z, Zhao Z, Liu X, Su Z, Shang X, Wen J (2012) Prediction of the outcome of antenatal hydronephrosis: significance of urinary EGF. Pediatr Nephrol 27:2251–2259. https://doi.org/10.1007/s00467-012-2243-4
Özkuvancı Ü, Dönmez Mİ, Ziylan O, Oktar T, Küçükgergin C, Çetin B, Erdem S, Seçkin Ş (2020) Can urinary biomarkers detect obstruction defined by renal functional loss in antenatal hydronephrosis? J Pediatr Urol 16:844.e1-844.e7. https://doi.org/10.1016/j.jpurol.2020.09.005
Gupta S, Jackson AR, DaJusta DG, McLeod DJ, Alpert SA, Jayanthi VR, McHugh K, Schwaderer AR, Becknell B, Ching CB (2018) Urinary antimicrobial peptides: potential novel biomarkers of obstructive uropathy. J Pediatr Urol 14:238.e1-238.e6. https://doi.org/10.1016/j.jpurol.2018.03.006
Kostic D, Beozzo GPNS, do Couto SB, Kato AHT, Lima L, Palmeira P, Krebs VLJ, Bunduki V, Francisco RPV, Zugaib M, Dénes FT, de Carvalho WB, Koch VHK (2019) The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants. J Pediatr Urol 15:242.e1-242.e9. https://doi.org/10.1016/j.jpurol.2019.03.009
Bieniaś B, Sikora P (2020) Selected metal matrix metalloproteinases and tissue inhibitors of metalloproteinases as potential biomarkers for tubulointerstitial fibrosis in children with unilateral hydronephrosis. Dis Markers 2020:9520309. https://doi.org/10.1155/2020/9520309
Yu L, Zhou L, Li Q, Li S, Luo X, Zhang C, Wu B, Brooks JD, Sun H (2019) Elevated urinary lipocalin-2, interleukin-6 and monocyte chemoattractant protein-1 levels in children with congenital ureteropelvic junction obstruction. J Pediatr Urol 15:44.e1-44.e7. https://doi.org/10.1016/j.jpurol.2018.10.007
Karakus S, Oktar T, Kucukgergin C, Kalelioglu I, Seckin S, Atar A, Ander H, Ziylan O (2016) Urinary IP-10, MCP-1, NGAL, cystatin-C, and KIM-1 levels in prenatally diagnosed unilateral hydronephrosis: the search for an ideal biomarker. Urology 87:185–192. https://doi.org/10.1016/j.urology.2015.09.007
Noyan A, Parmaksiz G, Dursun H, Ezer SS, Anarat R, Cengiz N (2015) Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis. J Pediatr Urol 11:249.e1-249.e6. https://doi.org/10.1016/j.jpurol.2015.02.021
Madsen MG, Nørregaard R, Palmfeldt J, Olsen LH, Frøkiær J, Jørgensen TM (2012) Urinary NGAL, cystatin C, β2-microglobulin, and osteopontin significance in hydronephrotic children. Pediatr Nephrol 27:2099–2106. https://doi.org/10.1007/s00467-012-2217-6
Radmayr C, Bogaert G, Dogan HS, Kocvara R et al (2019) EAU guidelines on paediatric urology. In: EAU Guidelines, edition presented at the annual EAU Congress Barcelona. EAU
Xie Y, Xue W, Shao X, Che X, Xu W, Ni Z, Mou S (2014) Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes. PLoS ONE 9:e112865. https://doi.org/10.1371/journal.pone.0112865
Diamond JR, Kees-Folts D, Ding G, Frye JE, Restrepo NC (1994) Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental hydronephrosis. Am J Physiol 266:F926-933. https://doi.org/10.1152/ajprenal.1994.266.6.F926
Lim AI, Tang SCW, Lai KN, Leung JCK (2013) Kidney injury molecule-1: more than just an injury marker of tubular epithelial cells? J Cell Physiol 228:917–924. https://doi.org/10.1002/jcp.24267
Aybek H, Aybek Z, Sinik Z, Demir S, Sancak B, Tuncay L (2006) Elevation of serum and urinary carbohydrate antigen 19–9 in benign hydronephrosis. Int J Urol 13:1380–1384. https://doi.org/10.1111/j.1442-2042.2006.01593.x
Pennemans V, Rigo J-M, Faes C, Reynders C, Penders J, Swennen Q (2013) Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue? Clin Chem Lab Med 51:1795–1802. https://doi.org/10.1515/cclm-2013-0157
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Sangeetha, G., Babu, R. Comparing accuracy of urinary biomarkers in differentiation of ureteropelvic junction obstruction from nonobstructive dilatation in children. Pediatr Nephrol 37, 2277–2287 (2022). https://doi.org/10.1007/s00467-022-05488-3
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DOI: https://doi.org/10.1007/s00467-022-05488-3