Urinary HIP/PAP and BD-1 indicate surgical success after pediatric ureteropelvic junction obstruction surgery
Sudipti Gupta, PhD, Lauren Nicassio, BS, Guillermo Yepes Junquera, D, Ashley Jackson, PhD, Molly Fuchs, MD, Daryl McLeod, MD MPH, Seth Alpert, MD, Rama Jayanthi, MD, Daniel DaJusta, MD, Kirk McHugh, PhD, Brian Becknell, MD PhD, Christina B. Ching, MD.
Nationwide Children's Hospital, Columbus, OH, USA.
Background: In a prior study, we found a panel of antimicrobial peptides (AMPs) to be significantly elevated in urinary tract obstruction from ureteropelvic junction obstruction (UPJO). We sought to see if these same AMPs would significantly decrease after successful surgical correction of UPJO to further test their utility as a biomarker of obstruction.
Methods: Pediatric patients (≤18 years old) undergoing surgical correction of an UJPO were recruited to take part in this study. Bladder urine from consenting/assenting patients was collected immediately prior to surgery and then at least 6 months after according to an IRB-approved protocol. Patients were excluded in the analysis if they demonstrated any signs of active urinary tract infection on urinalysis and/or symptomatology at time of collection. Based on prior studies demonstrating that the AMPs beta defensin 1 (BD-1), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), LL-37, and neutrophil gelatinase-associated lipocalin (NGAL) were significantly elevated in patients with UPJO versus unobstructed control patients, we performed enzyme-linked immunosorbent assays on these four AMPs to compare their expression before and after surgical intervention. AMP levels were normalized to urine creatinine. Results were analyzed with paired t test or Wilcoxon test using Graphpad software. A p-value of <0.05 was considered significant.
Results: 13 patients were included in the study; 9 were male (69%). Their 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 (average 27.4; range 7.8-45.3 months) after surgery and removal of all drainage tubes. All 13 patients had clinical improvement from before surgery and/or signs of improved hydronephrosis on post-operative imaging. We found that HIP/PAP and BD-1 were significantly decreased in post-surgical samples compared to pre-surgical samples (p=0.0215 and 0.0052, respectively, FIGURE); NGAL and LL-37 did not significantly change. The sensitivity/specificity of HIP/PAP for showing improvement/resolution of obstruction was 77% and 85%, respectively, while for BD-1 it was 75% and 67%, respectively.
Conclusions: HIP/PAP and BD-1 are significantly elevated in upper urinary tract obstruction but then significantly decrease with clinical and radiographic improvement and/or resolution of obstruction. These AMPs could serve as markers of successful surgical intervention. 
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