Yousef Lahoud1, Osamah Hussein1, Amjad Shalabi2, Omri Nativ3, Hoda Awad3, Mogher Khamaisi4, Ibrahim Matar5, Ofer Nativ6, Zaid Abassi7,8. 1. Department of Internal Medicine A, Faculty of Medicine, Ziv Hospital, Bar-Ilan University, Safed, Israel. 2. Department of General Surgery, Rambam Health Campus, Haifa, Israel. 3. Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, IIT, P.O. Box 9649, 31096, Haifa, Israel. 4. Department of Internal Medicine C, Institute of Endocrinology, Rambam Health Campus, Haifa, Israel. 5. Department of Surgery, Bnai Zion Hospital, 31096, Haifa, Israel. 6. Department of Urology, Bnai Zion Hospital, 47 Golomb St., 31096, Haifa, Israel. ofer.nativ@b-zion.org.il. 7. Research Unit, Rambam Health Campus, Haifa, Israel. abassi@tx.technion.ac.il. 8. Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, IIT, P.O. Box 9649, 31096, Haifa, Israel. abassi@tx.technion.ac.il.
Abstract
PURPOSE: Interruption of renal blood flow is often necessary during nephron sparing surgery (NSS) and can induce renal injury. This study examines whether tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator, exerts nephroprotective effects in patients undergoing NSS. METHODS: This non-randomized study included 49 patients with enhancing solid renal mass. All patients were subjected to open NSS during which clamping the renal artery was performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery. The other 27 patients underwent the same surgical procedure but did not receive tadalafil (controls). Urine samples were collected before surgery and following renal pedicle clamp removal. Urine levels of NGAL and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined. RESULTS: Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects, the elevation in serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as compared with NSS controls. CONCLUSIONS: Tadalafil exerts nephroprotective effects in AKI following NSS, as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation. Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients.
PURPOSE: Interruption of renal blood flow is often necessary during nephron sparing surgery (NSS) and can induce renal injury. This study examines whether tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator, exerts nephroprotective effects in patients undergoing NSS. METHODS: This non-randomized study included 49 patients with enhancing solid renal mass. All patients were subjected to open NSS during which clamping the renal artery was performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery. The other 27 patients underwent the same surgical procedure but did not receive tadalafil (controls). Urine samples were collected before surgery and following renal pedicle clamp removal. Urine levels of NGAL and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined. RESULTS: Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects, the elevation in serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as compared with NSS controls. CONCLUSIONS:Tadalafil exerts nephroprotective effects in AKI following NSS, as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation. Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients.
Authors: Dae Eun Choi; Jin Young Jeong; Beom Jin Lim; Sarah Chung; Yoon Kyung Chang; Sang Ju Lee; Ki Ryang Na; Seok Young Kim; Young Tai Shin; Kang Wook Lee Journal: Am J Physiol Renal Physiol Date: 2009-05-27
Authors: Venkata S Sabbisetti; Sushrut S Waikar; Daniel J Antoine; Adam Smiles; Chang Wang; Abinaya Ravisankar; Kazumi Ito; Sahil Sharma; Swetha Ramadesikan; Michelle Lee; Rebeccah Briskin; Philip L De Jager; Thanh Thu Ngo; Mark Radlinski; James W Dear; Kevin B Park; Rebecca Betensky; Andrzej S Krolewski; Joseph V Bonventre Journal: J Am Soc Nephrol Date: 2014-06-05 Impact factor: 10.121