Bladder dysfunction in patients with mitochondrial disease

• Research type

  Research Study

• Full title

  Bladder dysfunction in patients with mitochondrial disease

• IRAS ID

  220785

• Contact name

  Douglass M Turnbull

• Contact email

  doug.turnbull@newcastle.ac.uk

• Sponsor organisation

  Research and Development

• Duration of Study in the UK

  1 years, 0 months, 1 days

• Research summary

  Research Summary
  Contraction of the urinary bladder depends upon an interplay between the nervous system and smooth muscle within the bladder (detrusor muscle). Poor muscle function or under-activity, may lead to lower urinary tract symptoms (LUTS) or incomplete bladder emptying. LUTS frequently associated with detrusor underactivity include increased urinary frequency, overflow incontinence, decreased or interrupted urinary stream, hesitancy, and decreased sensation to void. These symptoms may also be associated with increased risk of developing urinary tract infections (UTI), urinary tract calculi, and renal impairment, in addition to adversely impacting patients’ quality of life. Since mitochondrial diseases are often characterised by loss of smooth muscle function, it is plausible to hypothesise that mitochondrial dysfunction may contribute to bladder dysfunction. However, mitochondrial involvement in bladder dysfunction remains poorly understood.

  In the MRC mitochondrial disease patient cohort (Mito Cohort), amongst 30 patients with m.3243A>G mutation presenting with bowel obstruction, six patients were noted to be in chronic urinary retention at presentation. A better understanding of prevalence and severity of bladder dysfunction, and associated influence on quality of life amongst patients with mitochondrial disease, may help deliver early appropriate interventions to improve their clinical management.

  In this study, adult patients with capacity attending the mitochondrial disease outpatient clinic at the Newcastle Hospitals NHS Foundation Trust, will be considered for inclusion. Patients will be asked to complete a validated gender-specific LUTS questionnaire and maintain a three-day bladder diary, where frequency and volume of voided urine will be recorded. Non-invasive assessment of bladder dysfunction will also be performed, which involves measuring the volume of urine they pass, and then using a portable ultrasound-based bladder scanner to measure the remaining urine in their bladder.

  Assessment of these measurements will help understand the prevalence and severity of bladder dysfunction and the impact on quality of life in mitochondrial disease patients.

  Summary of Results
  This prospective cohort study was performed at a single, quaternary, mitochondrial disease referral centre.

  Consecutive adult patients with genetically confirmed mitochondrial disease were enrolled.

  Data on baseline characteristics and disease burden were gathered. Lower Urinary Tract (LUT) dysfunction was assessed using the International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms (ICIQ-LUTS) questionnaire, bladder voiding efficiency (BVE), and bladder diaries. Patients with one or more feature of LUTS dysfunction were offered urodynamic testing.

  A total of 109 patients were included. Twenty-six percent of patients manifested at least one feature of LUT dysfunction, which was objectively confirmed in all 14 patients who consented to urodynamic investigation. Disease burden, defined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) demonstrated a linear relationship between NMDAS-gastrointestinal scores and LUTS scores (P<.001).
  Limitations include mutational heterogeneity across the patient cohort.

  This is the largest study exploring LUT in patients with mitochondrial disease and supports previous smaller studies suggesting LUT dysfunction is under-recognised in patients with mitochondrial disease and impacts considerably on their quality of life.

  In addition to a publication from which the above summary has been taken (Feeney C, Gorman G, Stefanetti R, et al. Lower urinary tract dysfunction in adult patients with mitochondrial disease. Neurourology and Urodynamics. 2020;1–11.
  https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbc7AuFoovXmgzveh-2BUeXUsuIgEuCynBwAySMCJjnBc-2BRKxj7_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKqmzbZ-2BmjgdOaJ0k0HSPKPnUQ7euN6gk-2FWpUfaWRmH-2B1C4WnNCGHT9gPOKqrWlmMxOk2Dm1ZNVKLDdd46wHBThFb8ChCAo-2FZiU0ud7IZ2FdxqJm-2BxFgGyX6Ba-2FBXGoUSGfuqhvn6ePz30xukG3044f7EFxu2XQsaIVY9hUQUID5g-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C0e1cfbac47194f76444408d9e4c62f30%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792362106344109%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=GQnEsdEb1DcfClFEO8OYd0S%2FSrMLIzeoYKEGq6DvnTs%3D&reserved=0

  the study was used to inform a clinical guideline for Lower Urinary Tract Dysfunction in Adult Mitochondrial Disease

  https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DouFFm-2FZqrUn2jjUD5TieZMbddcXjiE1UoDaXq1drMXITShC7XBm-2BprvsI5vsu0K6vFN2vfn-2F9LjerfdcB9V-2BvUJRqXwV04-2FpwDrlos56GJU-3Dw7Wr_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKqmzbZ-2BmjgdOaJ0k0HSPKPM-2FID0WtlKUJNhi-2BQLylMLY8o14rPPcyuppl3fVNwa5Fa2Ttp3ArbaYPVchog5YZv8lm5B3JbJvqgPQraW9dB64djP1KE7dS-2B540tYp8d2O0RKMaqxRAfoyvcmVwn3DkGEyVQXAD-2FEXyU-2B1AeDsZKrw-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C0e1cfbac47194f76444408d9e4c62f30%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792362106344109%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=DCUmKNdlfVSmy6WqnLbqm8gJzFu%2B7D55sE25ExPtFH4%3D&reserved=0

• REC name

  East Midlands - Derby Research Ethics Committee

• REC reference

  17/EM/0210

• Date of REC Opinion

  2 Jun 2017

• REC opinion

  Favourable Opinion