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P-2.47 The preventive effect of sirolimus on ureteral stricture formation

Sanem Cimen, Turkey

Associate Professor of Surgery
University of Health Sciences, Turkey
Diskapi Research and Training Hospital


Sanem Cimen is the founder of The Kidney Transplant program in Dıskapı Research and Training Hospital, one of the biggest government hospitals in Turkey, Ankara. She also gives lectures in University of Health Sciences on Abdominal Procurement Surgery, Kidney Transplantation and Deceased Donation.

She finished her general surgery training in Turkey, and moved to North America to gain expertise on transplant surgeries on 2011. Between 2011 and 2012 she worked as a surgical fellow at The Cleveland Clinic. Afterwards, she spent 4 years at the Dalhousie University of Canada where she performed over 200 deceased donor kidney transplantations. During her time in Canada she also got accustomed to ethical issues around DBD, DCD and related legislation.

Since 2016 she is appointed as an Associate Professor of Surgery with interest in Transplant and ESRD clinical research. As a lifelong learner, she also is a master’s student studying on Distance Education and e-Learning, which will give her the chance to connect with doctors and patients located in outreach areas of Turkey.


The preventive effect of sirolimus on ureteral stricture formation

Fatih Sandikci1, Sanem Cimen1, Sertac Cimen1, Ebru Gok Oguz3, Emine Ince Arik2, Abdurrahim Imamoglu1, Alihan Kokurcan1.

1Diskapi Research and Training Hospital Department of Urology and Transplantation, Health Sciences University , Ankara, Turkey; 2Diskapi Research and Training Hospital Department of Anesthesiology, Health Sciences University, Ankara, Turkey; 3Diskapi Research and Training Hospital Department of Nephrology, Health Sciences University, Ankara, Turkey

Introduction: Stricture of the transplant kidney ureter occurs in approximately 3% of transplant recipients. Risk factors for ureteral stricture include kidneys coming from marginal donors with advanced age and multiple comorbidities. Additionally, delayed graft function, presence of multiple renal arteries and direct injury during retrieval may increase the risk of this complication. Its clinical presentation is typical with elevated serum creatinine accompanied by hydronephrosis.
Although several open and endoscopic techniques have been described to manage this condition, ureteral stricture still increases short and long-term graft loss significantly.
An M-TOR inhibitor Sirolimus has been shown to reduce fibrosis. Since the mechanism of stricture formation is also through fibrosis, we analyzed the effect of this immunosuppressive drug on the prevention of ureteral strictures.
Methods: 32 New Zealand White rabbits (2500-3000grams) were used in the study. The rabbits were randomly assigned into four groups (n=8).
Group 1: A unilateral nephrectomy and subsequent full transection of the contralateral ureter was performed. The transected ureter was reconstructed over a double J ureteral stent by using interrupted 7/0 PDS stitches. 
Group 2: Same procedure with group 1 with Sirolimus- impregnated (1mg) stent placement
Group 3: A unilateral nephrectomy and subsequent full transection of the contralateral ureter was performed. The transected ureter was reconstructed without a stent and 1 ml of saline was instilled over the anastomosis.
Group 4: Same with group 3 with 1ml (1mg/ml) of Sirolimus solution instilled over the ureteric anastomosis (Figure 1).
On postoperative day 3, serum creatinine levels were measured. On postoperative day 7, an ultrasound of the kidney was performed to evaluate hydronephrosis. 
On postoperative day 21, all rabbits were explored to evaluate the ureteral anastomosis. Subsequently, all subjects were terminated, and full segment of the ureter was removed for histopathology assessments and tissue hydroxyproline level measurements. 
Results: Severe hydronephrosis and creatinine elevation were observed in group 3 compared to other groups (Figure 2). Histopathological evaluation of the specimens showed increased fibrosis scores in groups 1 and 3 (Figures 3&4). Tissue hydroxyproline levels in group 4 were found to be lower compared to other groups.
Conclusion: Sirolimus-impregnated double J stents may decrease ureteric stricture formation. This effect can be beneficial both in both kidney transplant and endourology practice.


[1] Giessing M. Transplant ureter stricture following renal transplantation: surgical options. Transplant Proc. 2011 Jan-Feb;43(1):383-6. doi: 10.1016/j.transproceed.2010.12.014.
[2] Lu S, Hu W, Zhang Z, Ji Z, Zhang T. Sirolimus-coated, poly(L-lactic acid)-modified polypropylene mesh with minimal intra-peritoneal adhesion formation in a rat model.Hernia. 2018 Dec;22(6):1051-1060. doi: 10.1007/s10029-018-1782-4. Epub 2018 May 18.
[3] Guler S, Cimen S, Hu Q, Venkatachalam AB, Hart-Matyas M, Alwayn I.Effects of mTOR Inhibitors in Prevention of Abdominal Adhesions.J Invest Surg. 2016 Oct;29(5):275-81. doi: 10.3109/08941939.2016.1149643. Epub 2016 Mar 16.
[4] Haller ST, Yan Y, Drummond CA, et al. Rapamycin Attenuates Cardiac Fibrosis in Experimental Uremic Cardiomyopathy by Reducing Marinobufagenin Levels and Inhibiting Downstream Pro-Fibrotic Signaling. J Am Heart Assoc. 2016;5(10):e004106. Published 2016 Sep 30. doi:10.1161/JAHA.116.004106


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