Aşırı Aktif Mesane Hastalarında İdrar Nerve Growth Faktör Düzeyi Ve Semptomlarla İlişkisi

Öz

Amaç: Mesane dokusunda ve idrarda yüksek seviyedeki nerve growth faktör ile alt üriner sistemi ilgilendiren patolojiler (Mesane Çıkım obstrüksiyonu, Aşırı Aktif Mesane, intersisyel sistit, ağrılı mesane sendromu) ilişkili bulunmuştur. Çalışmamızda, nerve growth faktör/kreatinin (NGF/kre) düzeyinin kontrol ve hasta grupları arasında karşılaştırılması ve hasta grubunda NGF/kre düzeyinin vücut kitle indeksi (VKİ), yaş, aşırı aktif mesane (AAM) tipleri (kuru-ıslak) ve semptom skorlarıyla (OAB-V8 ICI-SF) olan korelasyonunu saptamak amaçlanmıştır.

Materyal Metod: Aşırı aktif mesane hastalığı tanısı almış 27 kadın ve 26 kişilik kontrol grubundan oluşan prospektif kontrollü bir çalışmadır. Kontrol grubunda, kuru AAM hastalarında ve yaş AAM hastalarında ELİSA metoduyla idrar NGF düzeyleri ölçüldü. İdrar NGF düzeyleri idrar kreatinin seviyesine oranlanarak normalize edildi (ng/ mg kre). Hasta grubunun idrar NGF/kre düzeyleri, kontrol grubuyla karşılaştırıldı, ayrıca hasta grubunda NGF/kre düzeyinin; VKİ, yaş, AAM tipleri ve semptom skorlarıyla ilişkisi değerlendirildi.

Bulgular: Kontrol grubunda NGF/kre ortalama değeri 0,14±0,08 olarak saptanırken hasta grubunda NGF/kre değeri 0,40±0,4 olarak bulunmuş olup istatistiksel olarak anlamlı derecede yüksek bulunmuştur (p=0.0001). Elli-beş yaş altındaki hasta grubunda ortalama NGF/kre değeri 0,37±0,4 iken 55 yaş üzerindeki hasta grubunda ortalama değer 0,44±0,41 olarak bulunmuştur (p=0,904). VKİ 20-30 arasında olan hasta grubunda ortalama değer 0,27±0,26 iken VKİ 30’dan büyük olan hasta grubunda ortalama değer 0,52±0,48 olarak bulunmuştur (p=0,062). Kuru olan hasta grubunda ortalama değer 0,28±0,12 iken yaş olan hasta grubunda ortalama değer 0,42±0,43 olarak saptanmasına rağmen her iki grup (yaş-kuru) median NGF/kre değerleri arasında istatistiksel olarak anlamlı fark bulunmamıştır.(p=0,0.918).

Sonuç: NGF/Kre düzeyinin hasta grubunda kontrol grubundan anlamlı derecede yüksek çıkması, NGF/kre seviyesinin AAM hastalığında önemli bir tanısal belirteç olabileceğini göstermektedir.

Anahtar Kelimeler

• Aşırı aktif mesane,nerve growth faktör,yaş,VKİ

Urine nerve growth factor level and relation with overactive bladder disease symptoms

Öz

Background: High levels of nerve growth factor in urine and bladder tissue is associated with the pathologies of lower urinary tract such as bladder outlet obstruction, over aktive bladder, painful bladder syndrom and interstitial cystitis. In our study we aimed to compare the nerve growth factor creatinine (NGF/cre) level between the control and over active bladder (OAB) patients, and to determine the correlation between NGF / cre level and body mass index (BMI), age, OAB types (dry and wet) and symptom scores (OAB-V8, ICI-SF). Urinary NGF levels were measured in control group, dry and wet OAB patients.

Material and Methods: Twenty-seven women with a diagnosis of overactive bladder disease and 26 people in the control group were enrolled in this prospective controlled study. Urinary NGF levels were measured by ELISA method. NGF level were normalized by proportioning the NGF levels to urine creatinine (ng / mg Cre). Urinary NGF / cre level of patients were compared with the control group, as well as in patient group relationship between NGF / cre level and BMI, age, OAB subtypes and symptom scores were evaluated.

Results: Urinary NGF/Cr levels were significantly elevated in patients with OAB (0,40±0,4) compared to the controls (0.14 ± 0.08) (p=0.0001). Mean NGF/cre level in patients under the age of 55 was 0,37±0,4, while the mean NGF/cre level in patients over the age of 55 was 0,44±0,41 (p=0,904). There was no significant difference of serum NGF/cre levels in patients with BMI 20-30 (0,27±0,26) and BMI over the 30 (0,52±0,48) (p=0,062). Althought the mean NGF/cre level in dry-OAB patients and wet-OAB patient was respectively 0,28±0,12 and 0,42±0,43, there was no statistically significant difference between two groups’(wet-dry) median values of the NGF/cre levels (p=0,0.918).

Conclusions: Patients with overactive bladder had significantly higher urinary nerve growth factor levels compared to the control group. Urinary nerve growth factor levels could be a potential biomarker for the diagnosis of overactive bladder.

Anahtar Kelimeler

• Overactive bladder,nevre growth factor,age,BMI

Kaynakça

1. 1. Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecologicval Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010; 29: 4–20.
2. 2. Jo JK, Lee S, Kim YT, et al. Analysis of the Risk Factors for Overactive Bladder on the Basis of a Survey in the Community. Korean J Urol 2012 August; 53(8): 541–6.
3. 3. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327–36.
4. 4. Comperat E, Reitz A, Delcourt A, et al. Histologic features in the urinary bladder wall affected from neurogenic overactivity—a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A. Eur Urol 2006;50:1058–64.
5. 5. Apostolidis A, Jacques TS, Freeman A, et al. Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity. Eur Urol 2008;53:1245–53.
6. 6. Tyagi P, Barclay D, Zamora R, et al. Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol 2010;42:629-35.
7. 7. Lamb K, Gebhart GF, Bielefeldt K. Increased nerve growth factor expression triggers bladder overactivity. J Pain 2004;5:150-6.
8. 8. Cho KJ, Kim HS, Koh JS, Kim JC. Changes in urinary nerve growth factor and prostaglandin E(2) in women with overactive bladder after anticholinergics. Int Urogynecol J 2012 Jun; 21.

9. 9. Ghoniem G, Faruqui N, Elmissiry M, et al. Differential profile analysis of urinary cytokines inpatients with overactive bladder. Int Urogynecol J DOI 10.1007/s00192-011-1401-8.
10. 10. Liu HT, Kuo HC. Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology 2008;72:104–108.
11. 11. Giannantoni A, Di Stasi SM, Nardicchi V, et al. Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity. J Urol 2006;175:2341–4.
12. 12. Lowe EM, Anand P, Terenghi G, et al. Increased nevre growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol 1997;79:572–7.
13. 13. Chung YC, Fraser MO, Yu Y, Chancellor MB, de GroatWCand Yoshimura N. The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J Urol 2001;165:975.
14. 14. Liu HT, Chancellor MB, Kuo HC. Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder. BJU Int 2009;103:1668-72.
15. 15. Liu HT, Chen CY, Kuo HC. Urinary nevre growth factor in women with overactive bladder syndrome. BJU Int 2011;107:799-803.
16. 16. Dupont MC, Spitsbergen JM, Kim KB, et al. Histological and neurotrophic changes triggered by varying models of bladder inflammation. J Urol 2001;166:1111–8.
17. 17. Liu HT, Kuo HC. Urinary Nerve Growth Factor Level Could be a Potential Biomarker for Diagnosis of Overactive Bladder. J Urol. 2008 Jun;179(6):2270-4.
18. 18. Liu HT, Wang YS, Kuo HC - Tzu Chi. Nerve growth factor levels are increased in urine but not urothelium in patients with detrusor overactivity. Tzu Chi Medical Journal 2010;22:165-70.
19. 19. Chancellor MB, Oefelein MG, Vasavada S. Obesity is associated with a more severe overactive bladder disease state that is effectively treated with once-daily administration oftrospium chloride extended release. Neurourol Urodyn 2010;29: 551–4
20. 20. Coyne KS, Sexton CC, Bell JA, et al. The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial/ethnic group and age. Neurourol Urodyn 2012 Jul 27. doi: 10.1002/nau.22295. [Epub ahead of print]
21. 21. Swanson JG, Kaczorowski J, Skelly J, Finkelstein M.Urinary incontinence: common problem among women over 45. Can Fam Physician 2005;51:84-5
22. 22. Oktar T, Kocak T, Oner-Iyidogan Y, ve ark. Urinary nerve growth factor in children with overactive bladder: A promising, noninvasive and objective biomarker. J Pediatr Urol 2012 Jul 10. [Epub ahead of print].
23. 23. Kuo HC, Liu HT, Tyagi P, et al. Urinary nerve growth factor levels in urinary tract diseases with or without frequency urgency symptoms. LUTS 2010;2:88–94.