Prospective evaluation of candidate urine and cell markers in patients with interstitial cystitis enrolled in a randomized clinical trial of Bacillus Calmette Guerin (BCG).
We measured candidate urine biomarkers and bladder cell DNA cytometry in interstitial cystitis (IC) patients randomized to receive intravesical Bacillus Calmette Guerin (BCG) or placebo in a multicenter trial. Participants received 6 weekly instillations and were followed for 34 weeks. Urine was collected at baseline, prior to fourth treatment, and at study end. Antiproliferative factor (APF) activity was determined by 3H-thymidine incorporation assay; heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epidermal growth factor-like growth factor (EGF) levels were determined by ELISA. Cellular DNA content was measured by image analysis to determine the mean hyperdiploid fraction (HDF) of the urine cell pellet. Associations between marker levels, and treatment or symptoms, were examined. Baseline APF positivity rate and mean levels of the other biomarkers were similar to previous smaller studies. During the week 34 follow-up, mean HDF decreased (P = 0.0003) and HB-EGF increased (P < 0.0001); both correlated weakly with decreased urgency. There was no difference in any biomarker between symptom responders and non-responders, but the percentage of responders was low and not significantly different for BCG versus placebo. APF positivity, decreased HB-EGF, increased EGF, and increased HDF were confirmed at baseline in IC patients. Changes in HDF and HB-EGF levels correlated weakly with changes in urgency, but the low BCG response rate prevented identification of additional associations between biomarker changes and treatment or symptoms.
Keay
Susan
S
Department of Medicine, University of Maryland School of Medicine, 10 N. Greene Street, Baltimore, MD 21201, USA. skeay@medicine.umaryland.edu
Reeder
Jay E
JE
Koch
Kristopher
K
Zhang
Chen-Ou
CO
Grkovic
Daivd
D
Peters
Kenneth
K
Zhang
Yawei
Y
Kusek
John W
JW
Nyberg
Lee M
LM
Payne
Christopher K
CK
Propert
Kathleen J
KJ
D000283:Administration, Intravesical; D000328:Adult; D015415:Biomarkers / Q000652:urine; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D011446:Prospective Studies; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects
D015415:Biomarkers
BMC Urol. 2004 Apr 06;4:3
15068487
Urology. 2001 Jun;57(6 Suppl 1):15-21
11378044
Urology. 2000 May;55(5):643-6
10792070
BMC Urol. 2005 Apr 29;5:7
15862132
J Urol. 2003 Sep;170(3):810-5
12913705
Urology. 1998 Dec;52(6):1026-9
9836549
J Urol. 1988 Jul;140(1):203-6
3379688
J Urol. 1997 Dec;158(6):2045-50
9366309
Mead Johnson Symp Perinat Dev Med. 1988;(32):33-40
2485437
J Urol. 2002 Jun;167(6):2461-9
11992058
Gut. 1998 Feb;42(2):235-42
9536949
J Urol. 2005 Apr;173(4):1186-91
15758738
Urology. 2001 Jun;57(6 Suppl 1):9-14
11378043
Med Decis Making. 1996 Jan-Mar;16(1):78-85
8717602
J Urol. 2004 Dec;172(6 Pt 1):2256-60
15538243
J Urol. 1994 Dec;152(6 Pt 2):2262-6
7525999
J Urol. 1996 Dec;156(6):2073-8
8911393
Urology. 2002 Jul;60(1):46-51
12100920
J Clin Endocrinol Metab. 1977 Oct;45(4):668-72
303242
Urology. 1990 Jun;35(6):552-8
1693797
Br J Urol. 1995 May;75(5):622-30
7542132
J Urol. 2000 May;163(5):1440-4
10751853
Urology. 2001 Jun;57(6 Suppl 1):67-81
11378053
Acta Endocrinol (Copenh). 1990 Dec;123(6):643-8
2284889
J Urol. 2000 Dec;164(6):2112-8
11061938
Urology. 1998 Dec;52(6):974-8
9836539
Cornea. 2004 Nov;23(8):762-70
15502475
J Urol. 1997 Nov;158(5):1983-8
9334654
Pediatr Res. 1985 May;19(5):428-32
3873640
J Endocrinol. 1985 Aug;106(2):197-202
3874924