title: Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1.
abstract: OBJECTIVE
  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.affiliation: Department of Internal Medicine A, Faculty of Medicine, Ziv Hospital, Bar-Ilan University, Safed, Israel.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Lahoud
authors.affiliation: Department of Internal Medicine A, Faculty of Medicine, Ziv Hospital, Bar-Ilan University, Safed, Israel.
authors.forename: Osamah
authors.initials: O
authors.lastname: Hussein
authors.affiliation: Department of General Surgery, Rambam Health Campus, Haifa, Israel.
authors.forename: Amjad
authors.initials: A
authors.lastname: Shalabi
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, IIT, P.O. Box 9649, 31096, Haifa, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Nativ
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, IIT, P.O. Box 9649, 31096, Haifa, Israel.
authors.forename: Hoda
authors.initials: H
authors.lastname: Awad
authors.affiliation: Department of Internal Medicine C, Institute of Endocrinology, Rambam Health Campus, Haifa, Israel.
authors.forename: Mogher
authors.initials: M
authors.lastname: Khamaisi
authors.affiliation: Department of Surgery, Bnai Zion Hospital, 31096, Haifa, Israel.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Matar
authors.affiliation: Department of Urology, Bnai Zion Hospital, 47 Golomb St., 31096, Haifa, Israel. ofer.nativ@b-zion.org.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Nativ
authors.affiliation: Research Unit, Rambam Health Campus, Haifa, Israel. abassi@tx.technion.ac.il.|Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion, IIT, P.O. Box 9649, 31096, Haifa, Israel. abassi@tx.technion.ac.il.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002277:Carcinoma / Q000473:pathology / Q000601:surgery; D003404:Creatinine / Q000097:blood; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007511:Ischemia; D007680:Kidney Neoplasms / Q000473:pathology / Q000601:surgery*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009392:Nephrectomy / Q000009:adverse effects; D009399:Nephrons; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D000068581:Tadalafil / Q000627:therapeutic use*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D058986:Phosphodiesterase 5 Inhibitors; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D000068581:Tadalafil; D003404:Creatinine
keywords: Acute kidney injury; KIM-1; NGAL; Nephron sparing surgery; Tadalafil