Abstract: TH-PO652

Urothelial Injury Markers Are Elevated in Neurogenic Bladder Patients and Correlate with the Presence of Hydronephrosis

Session Information

  • Pediatric Nephrology
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 403 Pediatric Nephrology

Authors

  • Millner, Rachel, Nationwide Children's Hospital , Columbus, Ohio, United States
  • Preece, Janae, Nationwide Children's Hospital , Columbus, Ohio, United States
  • Gupta, Sudipti, Nationwide Children's Hospital , Columbus, Ohio, United States
  • Becknell, Brian, Nationwide Children's Hospital , Columbus, Ohio, United States
  • Ching, Christina B., Nationwide Children's Hospital , Columbus, Ohio, United States
Background

Neurogenic bladder (NGB) leads to varying bladder dysfunction and poses a high risk for chronic kidney disease. Urinary markers of urothelial injury are an intriguing approach to monitor NGB and associated urinary tract abnormalities. We hypothesize that urinary markers of urothelial integrity and injury are significantly altered in NGB vs non NGB patients and that these markers correlate with renal injury and degree of bladder dysfunction. We measured Uroplakin 3a (Upk3a), a structural urothelial protein, as a marker of urothelial integrity; and HIP/PAP, an antimicrobial peptide expressed solely by damaged urothelium, as a marker of urothelial injury.

Methods

We recruited 87 NGB patients for urine collection. Mean age was 8.7y (0.2-33y). Healthy controls consisted of 18 patients with a mean age of 13y (7-18y). Urine Upk3a and HIP/PAP were measured by ELISA. We estimated GFR using age appropriate equations and obtained urodynamics (UDS), VCUG, and renal ultrasound results by chart review. In NGB, we correlated UPK3a and HIP/PAP levels with GFR; presence of VUR, hydronephrosis, or scarring; and bladder dysfunction based on UDS classification. UDS classification was based on CDC protocol. Statistical analysis was performed by Mann Whitney U test, Spearman Correlation, and logistic regression; p<0.05 was considered statistically significant.

Results

Urinary HIP/PAP and UPK3a levels were significantly higher in NGB vs controls (p <0.005 and <0.0001, respectively) regardless of age, sex, or race. HIP/PAP was significantly associated with hydronephrosis (p=0.02) but not VUR, scarring, GFR, or UDS classification. Upk3a expression correlated only with presence of NGB. Type of bladder management (catheterization vs free voiding) did not impact UPk3a or HIP/PAP level. There was a negative correlation between presence of hydronephrosis and GFR (p=0.03).

Conclusion

NGB may be associated with urothelial exfoliation. HIP/PAP and UPK3a are potential, noninvasive biomarkers of NGB. Elevated levels of UPK3a and HIP/PAP in NGB are independent of renal function and may reflect alterations in urothelial remodeling or mechanical shedding of urothelium in response to bladder dysfunction. Furthermore, HIP/PAP may serve as an early, noninvasive marker of hydronephrosis in NGB, which is associated with reduced renal function.