Urinary TIMP-2 and MMP-2 are significantly associated with poor bladder compliance in adult patients with spina bifida

Neurourol Urodyn. 2019 Nov;38(8):2151-2158. doi: 10.1002/nau.24163. Epub 2019 Sep 4.

Abstract

Aims: To assess the predictive values of six urinary markers (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], matrix metalloproteinase 2 [MMP-2], tissue inhibitor metalloproteinase 2 [TIMP-2], transformation growth factor β-1 [TGF-B1], and prostaglandin 2 [PGE2]) for adverse urodynamic features and for upper urinary tract damage in adult patients with spina bifida.

Materials and methods: A single-center prospective trial was conducted from March 2015 to March 2017 including all consecutive adult patients with spina bifida seen for urodynamic testing. The urine was collected and stored at -80°C. A urodynamic and an upper urinary tract were systematically performed. At the end of the inclusion period, urines were defrosted and urinary nerve growth factor, BDNF, TIMP-2, and TGF-B1 were assessed using validated ELISA kits. The urinary markers levels were adjusted on the urinary creatinine level. Urinary MMP-2 levels were assessed by zymography.

Results: Fourty patients were included. Only TIMP-2 and MMP-2 were significantly associated with poor bladder compliance (P = .043 and P = .039, respectively). TIMP-2 was also the only urinary marker significantly associated with upper urinary tract damage on imaging (OR = 19.81; P = .02). Of all urodynamic parameters, bladder compliance and maximum detrusor pressure were the only ones associated with upper urinary tract damage on imaging (P = .01 and P = .02), The diagnostic performances of urinary TIMP-2 for upper urinary tract damage were slightly superior to PdetMax and bladder compliance with an area under the curve of 0.72.

Conclusion: Urinary TIMP-2 and MMP-2 were significantly associated with poor bladder compliance and urinary TIMP-2 was significantly associated with upper urinary tract damage. These findings support a pathophysiological role of extracellular matrix remodeling in poor bladder compliance of adult patients with spina bifida.

Keywords: compliance; neurogenic; spina bifida; urinary bladder; uroydnamics.

MeSH terms

  • Adult
  • Atrophy
  • Biomarkers / urine
  • Brain-Derived Neurotrophic Factor / urine
  • Compliance / physiology
  • Dinoprostone / urine
  • Female
  • Humans
  • Hydronephrosis / diagnostic imaging
  • Kidney / diagnostic imaging
  • Kidney / pathology
  • Male
  • Matrix Metalloproteinase 2 / urine
  • Middle Aged
  • Nerve Growth Factor / urine
  • Prospective Studies
  • Spinal Dysraphism / complications
  • Spinal Dysraphism / physiopathology*
  • Tissue Inhibitor of Metalloproteinase-2 / urine
  • Transforming Growth Factor beta1 / urine
  • Urinary Bladder, Neurogenic / etiology
  • Urinary Bladder, Neurogenic / physiopathology
  • Urinary Bladder, Neurogenic / urine*
  • Urodynamics
  • Young Adult

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • NGF protein, human
  • TGFB1 protein, human
  • TIMP2 protein, human
  • Transforming Growth Factor beta1
  • Tissue Inhibitor of Metalloproteinase-2
  • BDNF protein, human
  • Nerve Growth Factor
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Dinoprostone