Abstract
Objectives
The decision to surgically intervene in a hydronephrotic kidney in children is based on many debatable guidelines, some requiring repeated ultrasounds or renal scans. Urinary proteins have the potential to reflect renal disorders and hence can be the alternatives to such scans. Here, we aim to assess the role of urinary Neutrophil Gelatinase-Associated Lipocalin, Monocyte Chemoattractant Protein-1, and Interleukin-6 (IL-6) in such patients.
Methods
Seventeen children had obstructive hydronephrosis requiring pyeloplasty (UPJO), while seven were kept on conservative management in view of non-obstructive dilation (NOD). Urine samples were measured for the three urinary proteins at the time of presentation and following pyeloplasty using commercially available ELISA kits.
Results
The levels of all three urinary proteins were significantly higher in patients with UPJO children compared to the NOD group. Cut-off values to differentiate obstructive from non-obstructive hydronephrosis were obtained. A significant fall in the post-operative value of urinary IL-6 was also observed.
Conclusion
This study highlights the potentiality of urinary proteins as biomarkers in identifying children with hydronephrosis and picking out the ones with obstructive hydronephrosis who will require pyeloplasty. The drop in levels after pyeloplasty can be employed to evaluate the effectiveness of pyeloplasty when sent serially.
Similar content being viewed by others
Abbreviations
- USG:
-
Ultrasonography
- 99mTc-DTPA:
-
Diethylenetriaminepentaacetic acid diuretic renography
- NGAL:
-
Neutrophil Gelatinase-Associated Lipocalin
- MCP-1:
-
Monocyte Chemoattractant Protein-1
- IL-6:
-
Interleukin-6
- AKI:
-
Acute kidney injury
- ESRD:
-
End stage renal disease
- PUV:
-
Posterior urethral valve
- VUR:
-
Vesico-ureteral reflux
- UPJO:
-
Ureteropelvic junction obstruction
- UTI:
-
Urinary tract infection
- APD:
-
Anterior–posterior diameter
- NOD:
-
Non-obstructive dilation
- DRF:
-
Differential renal function
- IQR:
-
Interquartile range
- AUC:
-
Area under the curve
References
Buonafine M, Martinez-Martinez E, Jaisser F (2018) More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases. Clin Sci (Lond) 132:909–923. https://doi.org/10.1042/CS20171592
Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M (2008) Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 52:595–605. https://doi.org/10.1053/j.ajkd.2008.01.020
Satirapoj B (2018) Tubulointerstitial Biomarkers for Diabetic Nephropathy. J Diabetes Res 2018:1–6. https://doi.org/10.1155/2018/2852398
Tsakogiannis D, Kalogera E, Zagouri F, Zografos E, Balalis D, Bletsa G (2021) Determination of FABP4, RBP4 and the MMP-9/NGAL complex in the serum of women with breast cancer. Oncol Lett 21:85. https://doi.org/10.3892/ol.2020.12346
Anand S, Bajpai M, Khanna T, Kumar A (2020) Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as the emerging biomarkers. Pediatr Nephrol. https://doi.org/10.1007/s00467-020-04841-8
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
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
Cost NG, Noh PH, Devarajan P, Ivancic V, Reddy PP, Minevich E, Bennett M, Haffner C, Schulte M, DeFoor WR Jr (2013) Urinary NGAL levels correlate with differential renal function in patients with ureteropelvic junction obstruction undergoing pyeloplasty. J Urol 190:1462–1467. https://doi.org/10.1016/j.juro.2013.05.003
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):e1-6. https://doi.org/10.1016/j.jpurol.2015.02.021
Gerber C, Harel M, Lynch ML, Herbst KW, Ferrer FA, Shapiro LH (2016) Proximal tubule proteins are significantly elevated in bladder urine of patients with ureteropelvic junction obstruction and may represent novel biomarkers: A pilot study. J Pediatr Urol 12(120):e1-7. https://doi.org/10.1016/j.jpurol.2015.10.008
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
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
Bieniaś B, Sikora P (2018) Potential Novel Biomarkers of Obstructive Nephropathy in Children with Hydronephrosis. Dis Markers 2018:1015726. https://doi.org/10.1155/2018/1015726
Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine 29:313–326. https://doi.org/10.1089/jir.2008.0027
Grandaliano G, Gesualdo L, Bartoli F et al (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
Bartoli F, Penza R, Aceto G et al (2011) Urinary epidermal growth factor, monocyte chemotactic protein-1, and beta2-microglobulin in children with ureteropelvic junction obstruction. J Pediatr Surg 46:530–536. https://doi.org/10.1016/j.jpedsurg.2010.07.057
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
Mohammadjafari H, Rafiei A, Mousavi SA et al (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 55:670–676. https://doi.org/10.4111/kju.2014.55.10.670
Karakus S, Oktar T, Kucukgergin C et al (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
Sadeghi-Bojd S, Alijani E, Mahdavian MS (2018) Mean urinary cytokine MCP-1 in children with urinary tract obstruction and healthy children. Nephro-Urol Mon 10:e63607
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
Yu L, Zhou L, Li Q, Li S, Luo X, Zhang C et al (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
Sangeetha G, Babu R (2022) Comparing accuracy of urinary biomarkers in differentiation of ureteropelvic junction obstruction from nonobstructive dilatation in children. Pediatr Nephrol 37:2277–2287. https://doi.org/10.1007/s00467-022-05488-3 (Epub 2022 Mar 3 PMID: 35237864)
Author information
Authors and Affiliations
Contributions
Data collection and statistical analysis - Biangchwadaka Suchiang. Study conceptualisation and design - Manish Pathak. Interpretational of ELISA tests for biomarkers - Shailja Sharma. Interpretation of results - Manish Pathak, Rahul Saxena, Aliza Mittal, Kirtikumar Rathod, Arvind Sinha. Critical revision and Finalising the manuscript - Manish Pathak, Rahul Saxena, Shubhalaxmi Nayak, Avinash Jadhav, Arvind Sinha. Supervision and guidance - Manish Pathak, Arvind Sinha.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Suchiang, B., Pathak, M., Saxena, R. et al. Role of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Monocyte Chemoattractant Protein-1(MCP-1), and Interleukin-6(IL-6) as biomarkers in pediatric patients with hydronephrosis. Pediatr Surg Int 38, 1635–1641 (2022). https://doi.org/10.1007/s00383-022-05207-x
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-022-05207-x