MP77-10 URINARY AGRIN CLEAVAGE PRODUCTS PROVIDE PHENOTYPIC CHARACTERIZATION OF INTERSTITIAL CYSTITIS PATIENTS

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II1 Apr 2016MP77-10 URINARY AGRIN CLEAVAGE PRODUCTS PROVIDE PHENOTYPIC CHARACTERIZATION OF INTERSTITIAL CYSTITIS PATIENTS Laura Lamb, Peter Levanovich, Andrew Vereecke, Bernadette Zwaans, Sarah Bartolone, Kenneth Peters, and Michael Chancellor Laura LambLaura Lamb More articles by this author , Peter LevanovichPeter Levanovich More articles by this author , Andrew VereeckeAndrew Vereecke More articles by this author , Bernadette ZwaansBernadette Zwaans More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Kenneth PetersKenneth Peters More articles by this author , and Michael ChancellorMichael Chancellor More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1924AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Many patients with interstitial cystitis/bladder pain syndrome (IC/BPS) have pelvic floor muscle tenderness and may also have pelvic floor disorder. This can contribute to poor urination stream, need to push or bear down when voiding, painful intercourse, urinary urgency and frequency issues, pelvic pain, and incomplete bladder emptying. Agrin is involved in the organization of acetylcholine receptor clustering and plays a pivotal role in the formation and maintenance of neuromuscular junctions (NMJ), the cholinergic connections between nerves and muscles. When agrin is cleaved by neurotrypsin into two C-terminal cleavage fragments, there is a loss in the stabilization of the NMJ. Alterations in agrin expression results in loss of muscle coordination and is associated with neuromuscular diseases such as Amyotrophic Lateral Sclerosis and Sarcopenia. We sought to determine if agrin levels were altered in IC/BPS patients. METHODS Midstream urinary specimens were collected from 13 control and 17 female nonulcerative IC/BPS patients. IC/BPS patients had IC/BPS diagnosis for a minimum of 6 months and a total IC Symptom and Problem Indices (ICSI/PI) score greater than 16 (24.4±4.5). Samples were age and gender matched. Total LG3 containing C-terminal fragments were measured by enzyme-linked immunosorbent assay. Data was analyzed using Prism (GraphPad) software. RESULTS Total C-terminal fragments of agrin in urine samples were 137.4±28.13 pM in IC/BPS patients compared to 29.71±11.63 pM controls, resulting in a 4.62 fold increase (p=0.0014). Total agrin fragments also correlated with pain (p=0.0237) and frequency symptom scores (p=0.0373) of the ICSI. CONCLUSIONS Agrin plays an important role in the formation, maintenance, and reinforcement of NMJs, and IC/BPS patients have elevated urine levels of cleaved agrin. These results indicate that agrin depletion at the NMJ may be an important event in the development of pelvic floor dysfunction and pelvic pain in IC/BPS patients. Thus, agrin fragment detection in urine might be of diagnostic value. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1019-e1020 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Laura Lamb More articles by this author Peter Levanovich More articles by this author Andrew Vereecke More articles by this author Bernadette Zwaans More articles by this author Sarah Bartolone More articles by this author Kenneth Peters More articles by this author Michael Chancellor More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...