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Published in: Pediatric Nephrology 1/2020

01-01-2020 | Ureteropelvic Junction Obstruction | Original Article

The role of urinary NGAL and serum cystatin C in assessing the severity of ureteropelvic junction obstruction in infants

Authors: Antigoni Pavlaki, Nikoleta Printza, Evangelia Farmaki, Stella Stabouli, Anna Taparkou, Magdalini Sterpi, John Dotis, Fotios Papachristou

Published in: Pediatric Nephrology | Issue 1/2020

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Abstract

Background

The ideal management of ureteropelvic junction obstruction (UPJO) remains debatable. This prospective case-control study aimed to investigate if urinary levels of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and serum levels of cystatin C could distinguish surgical from non-surgical cases of UPJO and if they could detect earlier impairment of renal function.

Methods

Biomarkers were measured in the following age-matched groups: (a) 22 infants with surgical UPJO, at initial diagnosis and 12 months postoperatively (groups A1 and A2, respectively); (b) 19 infants with non-surgical UPJO (group B); and (c) 17 controls (group C). Based on serum cystatin C levels, estimated glomerular filtration rate (eGFR) was calculated.

Results

Urinary NGAL (uNGAL) was significantly higher in group A1 vs. group A2 (p = 0.02) and in group A1 vs. group C (p = 0.03), whereas there was no statistically significant difference between groups A2 and C (p = 0.77). Likewise, cystatin C levels were significantly higher in group A1 vs. group A2 and in group A1 vs. group C (p = 0.004 and p = 0.02, respectively), but no statistically significant difference between groups A2 and C (p = 0.82). uNGAL and serum cystatin C did not differ between groups B and A, nor did they differ between groups B and C. Cystatin C levels and eGFR of group A1 were significantly higher than those of group A2 and group C (p = 0.0001 and p = 0.02, respectively).

Conclusion

It seems that NGAL and cystatin C are able to distinguish patients who were treated surgically from healthy controls, and their levels appear to improve significantly following surgery.
Literature
1.
go back to reference Nguyen HT, Herndon CD, Cooper C, Gatti J, Kirsch A, Kokorowski P, Lee R, Perez-Brayfield M, Metcalfe P, Yerkes E, Cendron M, Campbell JB (2010) The Society for Fetal Urology consensus statement on the evaluation and management of antenatal hydronephrosis. J Pediatr Urol 6:212–231CrossRef Nguyen HT, Herndon CD, Cooper C, Gatti J, Kirsch A, Kokorowski P, Lee R, Perez-Brayfield M, Metcalfe P, Yerkes E, Cendron M, Campbell JB (2010) The Society for Fetal Urology consensus statement on the evaluation and management of antenatal hydronephrosis. J Pediatr Urol 6:212–231CrossRef
2.
go back to reference Braga LH, Ruzhynsky V, Pemberton J, Farrokhyar F, Demaria J, Lorenzo AJ (2014) Evaluating practice patterns in postnatal management of antenatal hydronephrosis: a national survey of Canadian pediatric urologists and nephrologists. Urology 83:909–914CrossRef Braga LH, Ruzhynsky V, Pemberton J, Farrokhyar F, Demaria J, Lorenzo AJ (2014) Evaluating practice patterns in postnatal management of antenatal hydronephrosis: a national survey of Canadian pediatric urologists and nephrologists. Urology 83:909–914CrossRef
3.
go back to reference Papachristou F, Pavlaki A, Printza N (2014) Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review. Biomarkers 19:531–540CrossRef Papachristou F, Pavlaki A, Printza N (2014) Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review. Biomarkers 19:531–540CrossRef
4.
go back to reference Carrie BJ, Golbetz HV, Michaels AS, Myers BD (1980) Creatinine: an inadequate filtration marker in glomerular diseases. Am J Med 69:177–182CrossRef Carrie BJ, Golbetz HV, Michaels AS, Myers BD (1980) Creatinine: an inadequate filtration marker in glomerular diseases. Am J Med 69:177–182CrossRef
5.
go back to reference Taylor AT (2014) Radionuclides in nephrourology, part 2: pitfalls and diagnostic applications. J Nucl Med 55:786e98 Taylor AT (2014) Radionuclides in nephrourology, part 2: pitfalls and diagnostic applications. J Nucl Med 55:786e98
6.
go back to reference Forster CS, Devarajan P (2017) Neutrophil gelatinase-associated lipocalin: utility in urologic conditions. Pediatr Nephrol 32:377–381CrossRef Forster CS, Devarajan P (2017) Neutrophil gelatinase-associated lipocalin: utility in urologic conditions. Pediatr Nephrol 32:377–381CrossRef
7.
go back to reference Sise ME, Forster C, Singer E, Sola-Del Valle D, Hahn B, Schmidt-Ott KM, Barasch J, Nickolas TL (2011) Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction. Nephrol Dial Transplant 26:4132–4135CrossRef Sise ME, Forster C, Singer E, Sola-Del Valle D, Hahn B, Schmidt-Ott KM, Barasch J, Nickolas TL (2011) Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction. Nephrol Dial Transplant 26:4132–4135CrossRef
8.
go back to reference 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:e112865CrossRef 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:e112865CrossRef
10.
go back to reference Turk V, Bode W (1991) The cystatins: protein inhibitors of cysteine proteinases. FEBS Lett 285:213–219CrossRef Turk V, Bode W (1991) The cystatins: protein inhibitors of cysteine proteinases. FEBS Lett 285:213–219CrossRef
11.
go back to reference Andersen TB (2012) Estimating renal function in children: a new GFR-model based on serum cystatin C and body cell mass. Dan Med J 59:B4486PubMed Andersen TB (2012) Estimating renal function in children: a new GFR-model based on serum cystatin C and body cell mass. Dan Med J 59:B4486PubMed
12.
go back to reference Salvador CL, Tøndel C, Rowe AD, Bjerre A, Brun A, Brackman D, Mørkrid L (2019) Estimating glomerular filtration rate in children: evaluation of creatinine- and cystatin C-based equations. Pediatr Nephrol 34:301–311CrossRef Salvador CL, Tøndel C, Rowe AD, Bjerre A, Brun A, Brackman D, Mørkrid L (2019) Estimating glomerular filtration rate in children: evaluation of creatinine- and cystatin C-based equations. Pediatr Nephrol 34:301–311CrossRef
13.
go back to reference Inker LA, Okparavero A (2011) Cystatin C as a marker of glomerular filtration rate: prospects and limitations. Curr Opin Nephrol Hypertens 20:631e9CrossRef Inker LA, Okparavero A (2011) Cystatin C as a marker of glomerular filtration rate: prospects and limitations. Curr Opin Nephrol Hypertens 20:631e9CrossRef
14.
go back to reference Slort PR, Ozden N, Pape L, Offner G, Tromp WF, Wilhelm AJ, Bokenkamp A (2012) Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction. Pediatr Nephrol 27:843–849CrossRef Slort PR, Ozden N, Pape L, Offner G, Tromp WF, Wilhelm AJ, Bokenkamp A (2012) Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction. Pediatr Nephrol 27:843–849CrossRef
15.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150CrossRef
16.
go back to reference den Bakker E, Gemke RJBJ, Bökenkamp A (2018) Endogenous markers for kidney function in children: a review. Crit Rev Clin Lab Sci 55:163–183CrossRef den Bakker E, Gemke RJBJ, Bökenkamp A (2018) Endogenous markers for kidney function in children: a review. Crit Rev Clin Lab Sci 55:163–183CrossRef
17.
go back to reference Gheissari A, Nematbakhsh M, Amir-Shahkarami SM, Alizadeh F, Merrikhi A (2013) Glomerular filtration rate and urine osmolality in unilateral ureteropelvic junction obstruction. Adv Biomed Res 2:78CrossRef Gheissari A, Nematbakhsh M, Amir-Shahkarami SM, Alizadeh F, Merrikhi A (2013) Glomerular filtration rate and urine osmolality in unilateral ureteropelvic junction obstruction. Adv Biomed Res 2:78CrossRef
18.
go back to reference Pavlaki A, Printza N, Farmaki E, Stabouli S, Taparkou A, Dotis J, Papachristou F (2017) Matrix metalloproteinases in ureteropelvic junction obstruction. Hippokratia 21:136–139PubMedPubMedCentral Pavlaki A, Printza N, Farmaki E, Stabouli S, Taparkou A, Dotis J, Papachristou F (2017) Matrix metalloproteinases in ureteropelvic junction obstruction. Hippokratia 21:136–139PubMedPubMedCentral
19.
go back to reference Fernbach SK, Maizels M, Conway JJ (1993) Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol 23:478–480CrossRef Fernbach SK, Maizels M, Conway JJ (1993) Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol 23:478–480CrossRef
20.
go back to reference Heinlen JE, Manatt CS, Bright BC, Kropp BP, Campbell JB, Frimberger D (2009) Operative versus nonoperative management of ureteropelvic junction obstruction in children. Urology 73:521–525CrossRef Heinlen JE, Manatt CS, Bright BC, Kropp BP, Campbell JB, Frimberger D (2009) Operative versus nonoperative management of ureteropelvic junction obstruction in children. Urology 73:521–525CrossRef
21.
go back to reference Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. J Am Soc Nephrol 4:1832–1843CrossRef Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. J Am Soc Nephrol 4:1832–1843CrossRef
22.
go back to reference Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRef Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRef
23.
go back to reference Staples A, LeBlond R, Watkins S, Wong C, Brandt J (2010) Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol 25:2321–2326CrossRef Staples A, LeBlond R, Watkins S, Wong C, Brandt J (2010) Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol 25:2321–2326CrossRef
24.
go back to reference Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Muñoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453CrossRef Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Muñoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453CrossRef
25.
go back to reference Grubb A, Blirup-Jensen S, Lindstrom V, Schmidt C, Althaus H, Zegers I (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med 48:1619–1621CrossRef Grubb A, Blirup-Jensen S, Lindstrom V, Schmidt C, Althaus H, Zegers I (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med 48:1619–1621CrossRef
26.
go back to reference Wasilewska A, Taranta-Janusz K, De˛bek W, Zoch-Zwierz W, Kuroczycka-Saniutycz E (2011) KIM-1 and NGAL: new markers of obstructive nephropathy. Pediatr Nephrol 26:579–586CrossRef Wasilewska A, Taranta-Janusz K, De˛bek W, Zoch-Zwierz W, Kuroczycka-Saniutycz E (2011) KIM-1 and NGAL: new markers of obstructive nephropathy. Pediatr Nephrol 26:579–586CrossRef
27.
go back to reference Madsen MG, Nørregaard R, Palmfeldt J, Olsen LH, Frøkiær J, Jørgensen TM (2012) Urinary NGAL, cystatin C, b2-microglobulin, and osteopontin significance in hydronephrotic children. Pediatr Nephrol 27:2099–2106CrossRef Madsen MG, Nørregaard R, Palmfeldt J, Olsen LH, Frøkiær J, Jørgensen TM (2012) Urinary NGAL, cystatin C, b2-microglobulin, and osteopontin significance in hydronephrotic children. Pediatr Nephrol 27:2099–2106CrossRef
28.
go back to reference 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 190:1462–1467CrossRef 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 190:1462–1467CrossRef
29.
go back to reference 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.e6CrossRef 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.e6CrossRef
30.
go back to reference 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.e6CrossRef 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.e6CrossRef
31.
go back to reference Bieniaś B, Sikora P (2018) Potential novel biomarkers of obstructive nephropathy in children with hydronephrosis. Dis Markers 13:1015726 Bieniaś B, Sikora P (2018) Potential novel biomarkers of obstructive nephropathy in children with hydronephrosis. Dis Markers 13:1015726
32.
go back to reference 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 87:185–192CrossRef 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 87:185–192CrossRef
33.
go back to reference Parvex P, Combescure C, Rodriguez M, Girardin E (2012) Is cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies? Nephrol Dial Transplant 27:3477–3482CrossRef Parvex P, Combescure C, Rodriguez M, Girardin E (2012) Is cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies? Nephrol Dial Transplant 27:3477–3482CrossRef
34.
go back to reference Parvex P, Combescure C, Rodriguez M, Birraux J, Girardin E (2014) Evaluation and predictive factors of renal function progression using cystatin C and creatinine in neonates born with CAKUT. Clin Nephrol 81:338–344CrossRef Parvex P, Combescure C, Rodriguez M, Birraux J, Girardin E (2014) Evaluation and predictive factors of renal function progression using cystatin C and creatinine in neonates born with CAKUT. Clin Nephrol 81:338–344CrossRef
35.
go back to reference Tomotaki S, Toyoshima K, Shimokaze T, Shibasaki J, Nagafuchi H (2017) Association between cord blood cystatin C levels and early mortality of neonates with congenital abnormalities of the kidney and urinary tract: a single-center, retrospective cohort study. Pediatr Nephrol 32:2089–2095CrossRef Tomotaki S, Toyoshima K, Shimokaze T, Shibasaki J, Nagafuchi H (2017) Association between cord blood cystatin C levels and early mortality of neonates with congenital abnormalities of the kidney and urinary tract: a single-center, retrospective cohort study. Pediatr Nephrol 32:2089–2095CrossRef
36.
go back to reference Cordeiro VF, Pinheiro DC, Silva GB Jr, Lima JW, Mota RM, Libório AB, Daher EF (2008) Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children. Clin Chim Acta 391:46–50CrossRef Cordeiro VF, Pinheiro DC, Silva GB Jr, Lima JW, Mota RM, Libório AB, Daher EF (2008) Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children. Clin Chim Acta 391:46–50CrossRef
37.
go back to reference Momtaz HE, Dehghan A, Karimian M (2016) Correlation of cystatin C and creatinine based estimates of renal function in children with hydronephrosis. J Renal Inj Prev 5:25–28CrossRef Momtaz HE, Dehghan A, Karimian M (2016) Correlation of cystatin C and creatinine based estimates of renal function in children with hydronephrosis. J Renal Inj Prev 5:25–28CrossRef
38.
go back to reference Chevalier RL (2016) Prognostic factors and biomarkers of congenital obstructive nephropathy. Pediatr Nephrol 31:1411–1420CrossRef Chevalier RL (2016) Prognostic factors and biomarkers of congenital obstructive nephropathy. Pediatr Nephrol 31:1411–1420CrossRef
Metadata
Title
The role of urinary NGAL and serum cystatin C in assessing the severity of ureteropelvic junction obstruction in infants
Authors
Antigoni Pavlaki
Nikoleta Printza
Evangelia Farmaki
Stella Stabouli
Anna Taparkou
Magdalini Sterpi
John Dotis
Fotios Papachristou
Publication date
01-01-2020
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-019-04349-w

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