Increased urinary transforming growth factor-beta(1) excretion in children with posterior urethral valves.
OBJECTIVE
Patients with posterior urethral valves (PUV) are at significant risk for progression to end-stage renal disease, despite early correction of the obstruction. Experimental models of urinary obstruction demonstrate increased renal expression of the profibrotic inflammatory mediator, transforming growth factor-beta(1) (TGF-beta(1)). Urinary TGF-beta(1) excretion is elevated in certain glomerular diseases, but has not been well studied in patients with obstructive lesions. The objective of this study was to examine urinary TGF-beta(1) excretion in children with PUV.


METHODS
Fourteen patients with PUV, aged 3.2 to 14.5 years, with estimated glomerular filtration rates (GFRs) of 12.8 to 139 mL/min/1.73 m(2) were enrolled. Sixteen normal subjects (9 male, 7 female), aged 4.3 to 20.5 years, served as controls. Total urinary TGF-beta(1) concentration was assayed by enzyme-linked immunoabsorbent assay, and expressed as a ratio to urinary creatinine concentration.


RESULTS
Urinary TGF-beta(1) excretion was significantly greater in patients with PUV (range 0 to 0.063, median 0.019 ng/mg urine creatinine) compared with that of healthy controls (range 0 to 0.022, median 0.005 ng/mg urine creatinine) (P <0.01). There was no correlation between urinary TGF-beta(1) excretion and estimated GFR, past urinary diversion surgery, or bladder wall thickening. Among healthy controls, urinary TGF-beta(1) was not correlated with age or gender.


CONCLUSIONS
Results from this study suggest that TGF-beta(1) may contribute to progressive renal insufficiency in patients with PUV. Further studies are indicated to determine if agents that affect TGF-beta(1) expression, such as angiotensin-converting enzyme inhibitors, can slow the progression of renal disease in PUV.
Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
K
K
MacRae Dell
B B
BB
Hoffman
M B
MB
Leonard
F N
FN
Ziyadeh
S L
SL
Schulman
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology; D012737:Sex Factors; D016212:Transforming Growth Factor beta / Q000502:physiology / Q000652:urine*; D014521:Urethra / Q000002:abnormalities*; D014524:Urethral Obstruction / Q000150:complications / Q000175:diagnosis / Q000652:urine*
D016212:Transforming Growth Factor beta; D003404:Creatinine