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

Neurogenic bladder (NB) post-meningomyelocele (MMC) repair is a major challenge and needs lifelong follow-up. Many cytokines have been implicated in the pathogenesis of NB. To avoid repeated urodynamic studies (UDS) and renal scans, we studied urinary tissue inhibitors of metalloproteinases-2 (TIMP-2) levels and correlated with urodynamic profiles to establish their efficacy.

Prospective case-control study on children between 6 months to 12 years of age, who were at least 6 months post-MMC repair and had NB on UDS. Patients were evaluated under 4 cohorts of 20 patients each: Group A (NB on treatment), Group B (NB not on treatment), Group C (no NB), and Group D (Controls). All groups underwent radiofrequency thermocoagulation, urine culture, ultrasonography. Urine samples were stored at -800°C and analyzed using a validated Human ELISA kit for TIMP-2.

Eighty patients with a mean age of 3.54 ± 2.1 years were studied. A common ultrasound finding was a thickened urinary bladder (33.3%). All UDS parameters showed a statistically significant differences between groups with NB (Groups A and B) and a group without NB (Group C). Analysis of TIMP-2 levels between individual groups was statistically significant. The area under the receiver operating characteristic curve between urinary TIMP-2 and cystometric parameters indicated that urinary TIMP-2 levels are highly diagnostic of NB. TIMP-2 value of 358.5 pg/ml was found to be the least value with 93.5 sensitivity and 86.2% specificity.

This study highlights the potential of urinary marker TIMP-2 as noninvasive and cost-effective test to initially diagnose and predict the progression of disease in NBs with reasonable sensitivity and specificity.