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.

TIMP‐2 as a noninvasive urinary marker for predicting neurogenic bladder in patients under follow‐up for spina bifida

“…In this study, the diagnostic performances of urinary TIMP-2 for upper urinary tract damage were slightly superior to Pdet Max and bladder compliance with an area under the curve of 0.72. 7 Akin to this, our study also demonstrated higher values of TIMP-2 in poorly compliant and high pressures bladders in the pediatric age group with the highest co-relation to bladder compliance. Peyronnet et al also indicated that the matrix metalloproteinase pathway could be a therapeutic target in this population known to poorly respond to pharmacological therapies.…”

“…These findings supported a pathophysiological role of extracellular matrix remodeling in poor bladder compliance of adult patients with spina bifida. In this study, the diagnostic performances of urinary TIMP‐2 for upper urinary tract damage were slightly superior to Pdet Max and bladder compliance with an area under the curve of 0.72 7 . Akin to this, our study also demonstrated higher values of TIMP‐2 in poorly compliant and high pressures bladders in the pediatric age group with the highest co‐relation to bladder compliance.…”

“…Peyronnet et al also indicated that the matrix metalloproteinase pathway could be a therapeutic target in this population known to poorly respond to pharmacological therapies. 7 Our study highlights the role of TIMP-2 in the evaluation of NB in children and is also the first of its kind to compare the values in age and sex-adjusted control population.…”

“…Akin to this, our study also demonstrated higher values of TIMP‐2 in poorly compliant and high pressures bladders in the pediatric age group with the highest co‐relation to bladder compliance. Peyronnet et al also indicated that the matrix metalloproteinase pathway could be a therapeutic target in this population known to poorly respond to pharmacological therapies 7 …”

“…Leak point detrusor pressure of more than 40 cm H 2 O was considered as a high-pressure bladder. Compliance of less than 20 ml/cm H 2 O was considered to be poorly compliant bladder based on a study by Peyronnet et al, 7 though, no cutoff value is recommended according to the International Continence Society guidelines. NAYAK ET AL.…”