ORIGINAL PAPER Hakan Vuruskan Æ Zulkuf Caliskan Æ Yakup Kordan Cuneyt Ozakin Æ Ismet Yavascaoglu Æ Bulent Oktay Elevated plasma concentrations of transforming growth factor-beta 1 in patients with unilateral ureteral obstruction Received: 28 February 2005 / Accepted: 3 May 2005 / Published online: 29 November 2005 Ó Springer-Verlag 2005 Abstract We measured plasma concentrations of TGF- beta 1 in patients with obstructive ureteral calculi and compared them with the plasma concentrations of healthy volunteers. The present study was a prospective study containing a homogenous group of patients with unilateral ureteral obstruction (UUO). The study con- sisted of patients with ureteral stones less than 7 mm in diameter that caused mild to moderate obstruction. All patients were referred by the emergency department of our hospital and examined between April 2003 and April 2004. The presence and characteristics of both stone and obstruction were determined by plain abdominal x-ray and gray-scale ultrasonography (US). Blood samples were collected from both patients and control individ- uals on admission and 1 week after conservative follow- up. The plasma TGF-beta 1 concentration was determined using a quantitative sandwich enzyme immunoassay specific for TGF-beta 1. There were 35 patients with 20 women and 15 men (average age 26.8±5.9 years), and 15 volunteers in the control group, with nine women and six men (average age 24.2±4.5 years). Average stone size was 5.6 mm±1.2 mm (range 3.5–7) for the patient group. US showed the presence of mild hydronephrosis in 24 and moderate hydronephrosis in 11 patients. Plasma concentrations of TGF-beta 1 in patients with ureteral obstruction (1,117±5.8 ng/ml, range 36–2,442 ng/ml) were significantly higher than those in the healthy con- trol group (32±4 ng/ml) on admission (P<0.001). There was a significant increase in TGF-beta 1 plasma concentrations in the patient group (33,525±6.8 ng/ml, range 1,107–73,288 ng/ml) after 1 week follow-up (P<0.001). Ureteral obstruction increases plasma TGF- beta 1 concentrations in patients with ureteral stones as in UUO models in animal studies. A concomitant treatment with an anti-fibrotic agent may reduce the incidence of renal injury during obstruction. Keywords TGF-beta 1 Æ Obstructive nephropathy Æ Ureteral calculus Æ Interstitial fibrosis Introduction Ureteral obstruction is a common clinical finding in urology practice. Ureteral calculus is the most frequent cause of unilateral ureteral obstruction (UUO). A con- servative approach can be used in a large number of patients having a ureteral stone with a diameter of less than 7 mm. In 98% of patients, such small ureteral stones are passed spontaneously [1, 2]. In clinical prac- tice, due to certain variables, damage to renal function is unpredictable with temporary obstruction. Most of our knowledge on UUO is derived from studies on experi- mental animal models. Increased expression of trans- forming growth factor-beta 1 (TGF-beta 1) in intrinsic renal cells or macrophages invading the kidney is due to elevated concentrations of angiotensin II. TGF-beta 1 is a key mediator of renal fibrosis in obstructive nephropathy. It increases the synthesis of matrix pro- teins while decreasing that of proteases which could degrade matrix [3, 4]. Recovery after relief of obstruc- tion is dependent on several factors, including the duration of the obstruction, its location, whether it is partial or complete, and the presence of intercurrent infection [5, 6]. At a very early stage of obstruction, a number of pharmacologic interventions, such as ACE inhibitors and antagonists, arginine, estrogenic protein- 1, pirferidon, and atorvastatin, may ameliorate the in- creased expansion of the interstitial volume, decrease the expression of TGF-beta 1, and downregulate the H. Vuruskan (&) Æ Z. Caliskan Æ Y. Kordan Æ I. Yavascaoglu B. Oktay Department of Urology, Medical Faculty, Uludag University, Bursa, Turkey E-mail: vuruskan@uludag.edu.tr Tel.: +90-224-4428146 Fax: +90-224-4428688 C. Ozakin Department of Microbiology, Medical Faculty, Uludag University, Bursa, Turkey Urol Res (2005) 33: 465–469 DOI 10.1007/s00240-005-0509-z