ENDOPYELOTOMY FAILURE IS ASSOCIATED WITH REDUCED TRANSFORMING GROWTH FACTOR-beta

Abstract

Purpose Approximately 15% of patients with ureteropelvic junction obstruction 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 smooth muscle regeneration and wound healing. To understand the pathophysiology of ureteropelvic junction obstruction and determine why endopyelotomy fails in some obstructed ureteropelvic junctions, TGF-beta expression in obstructed and normal ureteropelvic junction segments was compared. Materials and Methods Immunohistochemical staining using a rabbit polyclonal anti-TGF-beta was performed on deparafinfized 4 micro m. sections of paraffin blocked ureteropelvic junction segments. Human obstructed ureteropelvic junction segments were removed during primary pyeloplasties (11) and secondary pyeloplasties after endopyelotomy failure (11). Normal ureteropelvic junction segments were removed during nephrectomy 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 specimen. Results Mean TGF-beta expression plus or minus standard error of the mean was significantly increased (p <0.02) in obstructed ureteropelvic junctions from primary pyeloplasties (2.6 +/− 0.7) compared to normal ureteropelvic junctions (1.6 +/− 0.7), as expected. However, TGF-beta expression in the endopyelotomy failure group (1.8 +/− 0.6) was not significantly different from that in normal ureteropelvic junctions and was significantly lower (p <0.05) than that in obstructed ureteropelvic junctions from primary pyeloplasties. Conclusions Obstructed ureteropelvic junctions in cases of endopyelotomy failure have decreased expression of TGF-beta compared with other obstructed ureteropelvic junctions. These data suggest that an elevation of TGF-beta in obstructed ureteropelvic junctions may be necessary for successful tissue repair after endopyelotomy.