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Presentation Authors: Christopher J Chermansky*, Brian T Kadow, Mahendra Kashyap, Pradeep Tyagi, Pittsburgh, PA
Introduction: Micro RNAs (miRs) are non-coding strands of RNA involved in gene expression. Because of their relative stability in urine and serum, miRs are widely researched as promising biomarkers that may better help understand chronic diseases. The role of miRs in the pathology and treatment outcomes of onabotulinumtoxin-A (onaBoNT-A) in overactive bladder (OAB) patients is unknown. Here, we identified the miRs associated with elevated post-void residual volumes (PVRs) >200ml following intradetrusor injection of onaBoNT-A 100IU.
Methods: 14 female OAB patients with urgency urinary incontinence refractory to OAB drugs were consented for this study. Cystoscopic-guided punch bladder biopsy was obtained at the time of injecting 100 units of onaBoNT-A. RNA was extracted from the biopsy for measuring the expression of 13 miR species using TaqMan Universal PCR Master Mix in quantitative PCR. The miR species were selected for their known effect on neurotrophin expression and smooth muscle function. Relative expression for each miR was determined after normalizing to U6 small nuclear RNA. PVRs and urine Nerve Growth Factor (NGF) levels were measured at baseline and at the follow-up visit 3 weeks later.
Results: Consented 14 patients had a mean age of 66 years (Range 46-80 years). Of these patients, 9 maintained PVRs < 200mL (0-120 mL) after injection of onaBoNT-A to comprise the low PVR group. The other 5 patients developed PVRs > 200mL (213-391mL), and they comprise the high PVR group. The mean pre-procedure PVR was similar in both groups. Relative expression of miR221 and miR125b (see Figure 1) was upregulated by 11 and 2 fold, respectively (*p<0.05, Mann-Whitney U test) in patients who maintained low PVRs after onaBoNT-A. The expression of other 11 miR species and urine NGF levels at baseline were not significantly different between the two groups. Even though the NGF levels were similar in two groups but the 11 fold downregulation of miR221 may attenuate the action of NGF in high PVR group.
Conclusions: This study suggests that deficiency in the pretreatment expression of miR221 and miR125b may predispose OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies are needed to understand the role of each miR in OAB pathology and treatment outcomes.
Source Of Funding: Internal Funding from the Department of Urology at the University of Pittsburgh School of Medicine