S Gupta1, A R Jackson2, D G DaJusta3, D J McLeod3, S A Alpert3, V R Jayanthi3, K McHugh4, A R Schwaderer2, B Becknell2, C B Ching5. 1. Pediatric Urology Division, Pediatric Surgery Department at Nationwide Children's Hospital, Columbus, OH, USA; Center for Clinical and Translational Research at the Research Institute of Nationwide Children's Hospital, Columbus, OH, USA. 2. Center for Clinical and Translational Research at the Research Institute of Nationwide Children's Hospital, Columbus, OH, USA; Pediatric Nephrology Division, Pediatric Department at Nationwide Children's Hospital, Columbus, OH, USA. 3. Pediatric Urology Division, Pediatric Surgery Department at Nationwide Children's Hospital, Columbus, OH, USA. 4. Department of Biomedical Education & Anatomy, Ohio State University Medical School, USA. 5. Pediatric Urology Division, Pediatric Surgery Department at Nationwide Children's Hospital, Columbus, OH, USA; Center for Clinical and Translational Research at the Research Institute of Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: christina.ching@nationwidechildrens.org.
Abstract
INTRODUCTION: Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, there is mounting evidence to support their expression in noninfectious injury, with unclear meaning as to their function. It is possible that AMPs represent urothelial injury. Urinary tract obstruction is known to alter the urothelium; however, AMPs have not been evaluated for expression in this noninfectious injury. OBJECTIVE: A pilot study to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with nonobstructed controls. STUDY DESIGN: Bladder urine was collected from consenting/assenting pediatric patients with UPJO at intervention. Control bladder urines were obtained from age-matched and sex-matched healthy children without known obstruction or infection. Enzyme-linked immunosorbent assays were run for the following AMPs: β defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5); and normalized to urine creatinine. Results were analyzed with Student's t-test or Mann-Whitney U test, when appropriate, and receiver operating characteristic curves. A P-value of <0.05 was considered significant. RESULTS: Thirty bladder urine samples were obtained from children with UPJO at the time of decompressive intervention. Mean patient age was 4.7 years (range 0.3-18.4); 20 (67%) patients were male. Fifteen bladder urine samples were obtained from age-matched and sex-matched controls. Urinary AMP levels were significantly higher in UPJO patients than controls for BD-1 (P = 0.015), NGAL (P < 0.001), LL-37 (P < 0.001), and HIP/PAP (P = 0.046). Optimal threshold values of these AMPs were determined, with each demonstrating significant odds ratios of predicting urinary obstruction. DISCUSSION: Certain urinary AMPs are altered even in noninfectious urinary tract pathology. This represents a novel induction of AMP expression, as the current study is the first to report elevations in BD-1 and HIP/PAP in urinary tract obstruction. This suggests other roles for these AMPs outside of their antimicrobial properties, and likely is a reflection of the urothelial and tubular stress resulting from obstructive uropathy. CONCLUSIONS: Induction of AMPs BD-1, NGAL, LL-37, and HIP/PAP was found to occur in urinary tract obstruction. Further evaluation of AMP expression as a biomarker of uroepithelial injury outside of infection is indicated.
INTRODUCTION: Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, there is mounting evidence to support their expression in noninfectious injury, with unclear meaning as to their function. It is possible that AMPs represent urothelial injury. Urinary tract obstruction is known to alter the urothelium; however, AMPs have not been evaluated for expression in this noninfectious injury. OBJECTIVE: A pilot study to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with nonobstructed controls. STUDY DESIGN: Bladder urine was collected from consenting/assenting pediatric patients with UPJO at intervention. Control bladder urines were obtained from age-matched and sex-matched healthy children without known obstruction or infection. Enzyme-linked immunosorbent assays were run for the following AMPs: β defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5); and normalized to urine creatinine. Results were analyzed with Student's t-test or Mann-Whitney U test, when appropriate, and receiver operating characteristic curves. A P-value of <0.05 was considered significant. RESULTS: Thirty bladder urine samples were obtained from children with UPJO at the time of decompressive intervention. Mean patient age was 4.7 years (range 0.3-18.4); 20 (67%) patients were male. Fifteen bladder urine samples were obtained from age-matched and sex-matched controls. Urinary AMP levels were significantly higher in UPJO patients than controls for BD-1 (P = 0.015), NGAL (P < 0.001), LL-37 (P < 0.001), and HIP/PAP (P = 0.046). Optimal threshold values of these AMPs were determined, with each demonstrating significant odds ratios of predicting urinary obstruction. DISCUSSION: Certain urinary AMPs are altered even in noninfectious urinary tract pathology. This represents a novel induction of AMP expression, as the current study is the first to report elevations in BD-1 and HIP/PAP in urinary tract obstruction. This suggests other roles for these AMPs outside of their antimicrobial properties, and likely is a reflection of the urothelial and tubular stress resulting from obstructive uropathy. CONCLUSIONS: Induction of AMPs BD-1, NGAL, LL-37, and HIP/PAP was found to occur in urinary tract obstruction. Further evaluation of AMP expression as a biomarker of uroepithelial injury outside of infection is indicated.
Authors: Daryl J McLeod; Yuri V Sebastião; Christina B Ching; Jason H Greenberg; Susan L Furth; Brian Becknell Journal: Pediatr Nephrol Date: 2020-05-22 Impact factor: 3.714
Authors: Charan Kumar V Devarakonda; Emily R Shearier; Chaoran Hu; James Grady; Jeremy L Balsbaugh; John H Makari; Fernando A Ferrer; Linda H Shapiro Journal: J Pediatr Urol Date: 2020-06-11 Impact factor: 1.830
Authors: Zuzana Seifriedova; Hana Flogelova; Jan Sarapatka; Oldrich Smakal; Vladimir Student Journal: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub Date: 2022-02-03 Impact factor: 1.648