Transforming growth factor-β1 in congenital ureteropelvic junction obstruction: diagnosis and follow-up

OBJECTIVE: To assess the role of transforming growth factor-β1 (TGF-β1) in congenital ureteropelvic junction obstruction at diagnosis and during postoperative follow-up. MATERIAL AND METHODS: We conducted a case-control study including 19 patients with a mean age of 6.7 years and 19 matched controls. All patients presented negative voiding cystourethrography, obstructive diuretic renogram and underwent dismembered pyeloplasty. Urinary TGF-β1 and other markers were measured pre-, intra- and postoperatively. RESULTS: The mean bladder urine TGF-β1 concentration in obstructed patients prior to pyeloplasty was higher than in controls (92.5 pg/mL ± 16.8 vs. 35.8 pg/mL ± 16.2; p = 0.0001). The mean renal pelvic urine TGF-β1 concentration in the hydronephrotic kidney was higher than in the preoperative bladder urine sample (122.3 pg/mL ± 43.9 vs. 92.5 pg/mL ± 16.8; p = 0.036). Postoperative mean TGF-β1 concentration was significantly lower than preoperative TGF-β1 (48.7 pg/mL ± 13.1 vs. 92.5 pg/mL ± 16.8; p = 0.0001). CONCLUSION: TGF-β1 is a cytokine leading to renal fibrosis. The measurement of urinary TGF-β1 could become a useful tool for the diagnosis of obstructive hydronephrosis and the evaluation of the parenchyma function status, pre and postoperatively.

Biochemical-molecular markers in unilateral ureteral obstruction

Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta(TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations.