Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy.
OBJECTIVE
The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine.


METHODS
Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test (P < .05).


RESULTS
Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 (P = .029), including any MMP other than 63 kDa and 65 kDa (P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs (P = .029).


CONCLUSIONS
Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.
Nicksa
Grace A
GA
Department of Surgery, Children's Hospital Boston & Harvard Medical School, Boston, MA 02115, USA.
Yu
David C
DC
Curatolo
Adam S
AS
McNeish
Brendan L
BL
Barnewolt
Carol E
CE
Valim
Clarissa
C
Buchmiller
Terry L
TL
Moses
Marsha A
MA
Fauza
Dario O
DO
D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000652:urine; D020780:Matrix Metalloproteinase 9 / Q000652:urine; D020782:Matrix Metalloproteinases / Q000652:urine*; D053505:Matrix Metalloproteinases, Secreted / Q000652:urine; D011247:Pregnancy; D012756:Sheep; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000652:urine; D016216:Ultrasonography, Prenatal; D014570:Urologic Diseases / Q000151:congenital* / Q000201:enzymology / Q000652:urine*
D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9