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

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.

• Authors: Benoit Peyronnet, Claire Richard, Claude Bendavid, Florian Naudet, Juliette Hascoet, Charlène Brochard, Nelly Senal, Magali Jezequel, Quentin Alimi, Zine-Eddine Khene, Anne Corlu, Bruno Clément, Laurent Siproudhis, Guillaume Bouguen, Jacques Kerdraon, Andrea Manunta, Xavier Gamé
• Journal: Neurourology and urodynamics (Neurourol Urodyn) Vol. 38 Issue 8 Pg. 2151-2158 (11 2019) ISSN: 1520-6777 [Electronic] United States
• PMID: 31486131 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• 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

Topics

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