title: Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients.
abstract: OBJECTIVE
  Sacral neuromodulation (SNM) may improve interstitial cystitis/painful bladder syndrome (IC/BPS) symptoms of urinary frequency, urgency and perhaps even pain, but objective measures of improvement are lacking. We evaluated the potential for urinary chemokines to serve as measures of treatment response over time to SNM.
  
  
  METHODS
  Women with IC/BPS undergoing SNM consented for this study. Three-day bladder/pain diaries were collected at baseline and validated Interstitial Cystitis Symptom Problem Index (ICSPI) scores and mid-stream urine specimens were collected at baseline and at 24 weeks after successful implant. Collected urine was screened for infection by dipstick and analyzed for chemokines by luminex xMAP analysis.
  
  
  RESULTS
  At baseline (n = 16), urine levels of CXCL-1 positively correlated with pain score (r = 0.63, P = 0.009), urgency (r = 0.61, P = 0.01), ICSPI (r = 0.43, P = 0.09) and daily voids (r = 0.44, P = 0.08). ICSPI and pain scores also positively correlated with sIL-1ra (r = 0.50, P = 0.04) and monocyte chemotactic protein-1 (MCP-1) or CCL2 positively correlated with daily voids (r = 0.45, P = 0.07) only. At 24 weeks, the median ICSPI index fell from 28 to 15 (n = 7, P = 0.008). Urine levels of sIL-1ra (633.8 ± 188.2 vs. 149.9 ± 41.62 pg/mL) and MCP-1 (448.3 ± 11.6 vs. 176.9 ± 46.16 pg/mL) and CCL5 (20.78 ± 4.09 vs. 11.21 ± 4.12 pg/mL) were also significantly reduced at the follow-up relative to baseline values (P = 0.04). Multivariable analysis of data revealed that sIL-1ra and MCP-1 together explained the majority of variance in data. Levels of CXCL-1, CXCL-10, interleukin (IL)-8, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) were also reduced at 24 weeks, but differences were not significant.
  
  
  CONCLUSIONS
  Concomitant decrease in urine levels of chemokines especially MCP-1 was associated with treatment response of SNM. These results support the role of chemokines as downstream effectors of neuromodulation response and could serve as potential non-invasive measures of treatment response.
  
  
  BACKGROUND
  NCT01739946.
authors.affiliation: William Beaumont Hospital, Royal Oak, Michigan, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Peters
authors.affiliation: William Beaumont Hospital, Royal Oak, Michigan, USA.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Jayabalan
authors.affiliation: William Beaumont Hospital, Royal Oak, Michigan, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Bui
authors.affiliation: William Beaumont Hospital, Royal Oak, Michigan, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Killinger
authors.affiliation: William Beaumont Hospital, Royal Oak, Michigan, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chancellor
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D018925:Chemokines / Q000652:urine*; D018856:Cystitis, Interstitial / Q000628:therapy* / Q000652:urine; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008160:Lumbosacral Plexus; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines
keywords: chemokines; neuromodulation; outcome measures; urine