In the pediatric patient whose ureteropelvic junction obstruction (UPJO) is not always symptomatic, imaging is the most common means of detecting surgical success. There is interest, however, in other means of post-operative monitoring. A panel of antimicrobial peptides (AMPs) has been previously found to be elevated in UPJO, but the impact of surgical correction on these AMPs is unknown.
To determine if elevated levels of candidate urinary AMP biomarkers of urinary tract obstruction decrease following UPJO repair.
Pediatric patients undergoing surgical correction of an UPJO were recruited for participation. Bladder urine from uninfected consenting/assenting patients was collected immediately prior to surgery and then at least 6 months afterward. Based on prior studies demonstrating significant elevation of beta defensin 1 (BD-1), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in patients with UPJO versus control patients, we performed enzyme-linked immunosorbent assays on these four AMPs to compare their expression before and after surgical intervention. If found to significantly decrease, AMP levels were compared to healthy controls. AMP levels were normalized to urine creatinine. Results were analyzed with paired t test or Wilcoxon test using Graphpad software. Correlation was calculated using Pearson or Spearman correlation. A p-value of <0.05 was considered significant.
13 UPJO patients were included in this study; 9 were male (69%). Age at surgery was a median of 4.3 years (average 6.1, range 0.4–18.4 years). Follow-up urine samples were collected a median of 27.4 months after surgery (average 27.4; range 7.8–45.3 months). All 13 patients had clinical improvement and/or signs of improved hydronephrosis on post-operative imaging. HIP/PAP and BD-1 significantly decreased in post-surgical samples compared to pre-surgical samples (p = 0.02 and 0.01, respectively); NGAL and LL-37 did not significantly change. Overall, HIP/PAP decreased in 12 patients (92%) and BD-1 decreased in 11 patients (85%). BD-1 levels after successful repair were not different from healthy controls (p = 0.06).
Urinary biomarkers of obstruction should detect significant obstructive pathology as well as reflect its resolution. This would enable their use in post-operative monitoring and augment current methods of determining successful surgical outcome through imaging.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Pediatric Urology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Contributions of the transplant registry: the 2006 annual report of the North American pediatric renal trials and collaborative studies (NAPRTCS).Pediatr Transplant. 2007; 11: 366-373
- Results of systematic screening for minor degrees of fetal renal pelvis dilatation in an unselected population.Am J Obstet Gynecol. 2003; 188: 242-246
- Antenatal ultrasonography to detect fetal renal abnormalities: a prospective screening programme.BMJ. 1989; 298: 1421-1423
- The Society for Fetal Urology consensus statement on the evaluation and management of antenatal hydronephrosis.J Pediatr Urol. 2010; 6: 212-231
- A prospective study comparing ultrasound, nuclear scintigraphy and dynamic contrast enhanced magnetic resonance imaging in the evaluation of hydronephrosis.J Urol. 2003; 170: 1330-1334
- Human fetal compensatory renal growth.J Urol. 1993; 150: 790-792
- Fetal compensatory renal growth due to unilateral ureteral obstruction.J Urol. 1993; 150: 597-600
- Innate immunity and urinary tract infection.Pediatr Nephrol. 2019; (In press)
- The innate immune response during urinary tract infection and pyelonephritis.Pediatr Nephrol. 2014; 29: 1139-1149
- Emerging urinary markers of renal injury in obstructive nephropathy.Biomed Res Int. 2014; 2014: 303298
- Expression of pancreatitis associated proteins in urothelium and urinary afferent neurons following cyclophosphamide induced cystitis.J Urol. 2008; 179: 1603-1609
- Urinary antimicrobial peptides: potential novel biomarkers of obstructive uropathy.J Pediatr Urol. 2018; 14: 238 e1-238 e6
- Scintigraphic renal function after unilateral pyeloplasty in children: a systematic review.BJU Int. 2008; 102: 862-868
- Is routine postoperative diuresis renography indicated in all adult patients after pyeloplasty for ureteropelvic junction obstruction?.Urology. 2015; 85: 246-251
- Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review.Biomarkers. 2014; 19: 531-540
- Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury.Am J Physiol Ren Physiol. 2006; 290: F517-F529
- Expression and significance of the HIP/PAP and RegIIIgamma antimicrobial peptides during mammalian urinary tract infection.PloS One. 2015; 10e0144024
- Localization of expression of human beta defensin-1 in the pancreas and kidney.J Pathol. 1998; 186: 99-103
- Human beta-defensin-1: an antimicrobial peptide of urogenital tissues.J Clin Invest. 1998; 101: 1633-1642
- The uroplakin plaque promotes renal structural integrity during congenital and acquired urinary tract obstruction.Am J Physiol Ren Physiol. 2018; 315: F1019-F1031
- Unilateral ureteral obstruction evokes renal tubular apoptosis via the enhanced oxidative stress and endoplasmic reticulum stress in the rat.Neurourol Urodyn. 2011; 30: 472-479
- Urinary NGAL levels correlate with differential renal function in patients with ureteropelvic junction obstruction undergoing pyeloplasty.J Urol. 2013; 190: 1462-1467
- Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons.Kidney Int. 2009; 75: 285-294
- Urinary NGAL, cystatin C, beta2-microglobulin, and osteopontin significance in hydronephrotic children.Pediatr Nephrol. 2012; 27: 2099-2106
- Role of urinary cathelicidin LL-37 and human beta-defensin 1 in uncomplicated Escherichia coli urinary tract infections.Infect Immun. 2014; 82: 1572-1578
- Urinary IP-10, MCP-1, NGAL, cystatin-C, and KIM-1 levels in prenatally diagnosed unilateral hydronephrosis: the search for an ideal biomarker.Urology. 2016; 87: 185-192
- The role of urinary KIM-1, NGAL, CA19-9 and beta2-microglobulin in the assessment of ureteropelvic junction obstruction in adults.Biomarkers. 2017; 22: 682-688
- KIM-1 and NGAL: new markers of obstructive nephropathy.Pediatr Nephrol. 2011; 26: 579-586
- Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes.PloS One. 2014; 9e112865
- Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis.J Pediatr Urol. 2015; 11: 249 e1-6
Published online: March 29, 2020
Accepted: March 10, 2020
Received: November 5, 2019
© 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.