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Increased urinary transforming growth factor-beta(1) excretion in children with posterior urethral valves
K MacRae Dell1, B B Hoffman, M B Leonard
1Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Insights
Children with posterior urethral valves (PUV) show higher urinary transforming growth factor-beta(1) (TGF-beta(1)) levels. This suggests TGF-beta(1) may worsen kidney disease progression in PUV patients.
Area of Science:
- Pediatric Nephrology
- Renal Pathophysiology
- Urology
Background:
- Posterior urethral valves (PUV) pose a significant risk for end-stage renal disease, even after corrective surgery.
- Experimental models indicate that urinary obstruction increases renal expression of transforming growth factor-beta(1) (TGF-beta(1)).
- Elevated urinary TGF-beta(1) is observed in some glomerular diseases, but its role in obstructive uropathy is less understood.
Purpose of the Study:
- To investigate urinary TGF-beta(1) excretion levels in children diagnosed with PUV.
- To compare TGF-beta(1) levels in PUV patients with those of healthy controls.
Main Methods:
- Enrolled fourteen children with PUV (aged 3.2–14.5 years) and sixteen healthy controls (aged 4.3–20.5 years).
- Assayed total urinary TGF-beta(1) concentration using enzyme-linked immunosorbent assay.
- Expressed TGF-beta(1) levels as a ratio to urinary creatinine concentration.
Main Results:
- Urinary TGF-beta(1) excretion was significantly higher in PUV patients (median 0.019 ng/mg) compared to controls (median 0.005 ng/mg) (P <0.01).
- No correlation was found between urinary TGF-beta(1) and estimated GFR, prior urinary diversion, or bladder wall thickening in PUV patients.
- In controls, urinary TGF-beta(1) did not correlate with age or gender.
Conclusions:
- The findings suggest that TGF-beta(1) may play a role in the progressive renal insufficiency observed in children with PUV.
- Further research is warranted to explore therapeutic strategies targeting TGF-beta(1), such as ACE inhibitors, to mitigate renal disease progression in PUV.
Objectives:
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.