ENDOPYELOTOMY FAILURE IS ASSOCIATED WITH REDUCED TRANSFORMING-GROWTH-FACTOR-BETA

Purpose: Approximately 15% of patients with ureteropelvic junction obs truction have endopyelotomy failure and require an additional surgical procedure to remove the obstruction. Transforming growth factor-beta (TGF-beta), a cytokine which stimulates mesenchymal cell proliferation and extracellular matrix deposition, increases in the renal pelvis in response to obstruction. However, TGF-beta also is implicated in smoo th muscle regeneration and wound healing. To understand the pathophysi ology of ureteropelvic junction obstruction and determine why endopyel otomy fails in some obstructed ureteropelvic junctions, TGF-beta expre ssion in obstructed and normal ureteropelvic junction segments was com pared. Materials and Methods: Immunohistochemical staining using a rab bit polyclonal anti-TGF-P was performed on deparafinfized 4 mu m. sect ions of paraffin blocked ureteropelvic junction segments. Human obstru cted ureteropelvic junction segments were removed during primary pyelo plasties (11) and secondary pyeloplasties after endopyelotomy failure (11). Normal ureteropelvic junction segments were removed during nephr ectomy for purposes unrelated to obstruction (11). Grading on a scale of 0 to 4 was performed by a physician blinded to the source of the sp ecimen. Results: Mean TGF-P expression plus or minus standard error of the mean was significantly increased (p <0.02) in obstructed ureterop elvic junctions from primary pyeloplasties (2.6 +/- 0.7) compared to n ormal ureteropelvic junctions (1.6 +/- 0.7), as expected. However, TGF -P expression in the endopyelotomy failure group (1.8 +/- 0.6) was not significantly different from that in normal ureteropelvic junctions a nd was significantly lower (p <0.05) than that in obstructed ureterope lvic junctions from primary pyeloplasties. Conclusions: Obstructed ure teropelvic junctions in cases of endopyelotomy failure have decreased expression of TGF-beta compared with other obstructed ureteropelvic ju nctions. These data suggest that an elevation of TGF-beta in obstructe d ureteropelvic junctions may be necessary for successful tissue repai r after endopyelotomy.