Skip to main content
Erschienen in: World Journal of Urology 12/2015

01.12.2015 | Original Article

Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1

verfasst von: Yousef Lahoud, Osamah Hussein, Amjad Shalabi, Omri Nativ, Hoda Awad, Mogher Khamaisi, Ibrahim Matar, Ofer Nativ, Zaid Abassi

Erschienen in: World Journal of Urology | Ausgabe 12/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Lau WK, Blute ML, Weaver AL et al (2000) Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 75:1236–1242CrossRefPubMed Lau WK, Blute ML, Weaver AL et al (2000) Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 75:1236–1242CrossRefPubMed
2.
Zurück zum Zitat Becker F, Siemer S, Humke U et al (2006) Elective nephron-sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol 49:308–313CrossRefPubMed Becker F, Siemer S, Humke U et al (2006) Elective nephron-sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol 49:308–313CrossRefPubMed
3.
Zurück zum Zitat Weight CJ, Larson BT, Fergany AF et al (2010) Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses. J Urol 183:1317–1323CrossRefPubMed Weight CJ, Larson BT, Fergany AF et al (2010) Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses. J Urol 183:1317–1323CrossRefPubMed
4.
Zurück zum Zitat Schrier RW, Wang W, Poole B, Mitra A. (2004) Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 2004 Jul;114(1):5–14. Review. Erratum in: J Clin Invest. 114(4):598 Schrier RW, Wang W, Poole B, Mitra A. (2004) Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 2004 Jul;114(1):514. Review. Erratum in: J Clin Invest. 114(4):598
5.
Zurück zum Zitat Lameire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 4(365):417–430CrossRef Lameire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 4(365):417–430CrossRef
7.
Zurück zum Zitat Bellomo R, Cass A, Cole L et al (2009) RENAL replacement therapy study investigators. N Engl J Med 361:1627–1638CrossRefPubMed Bellomo R, Cass A, Cole L et al (2009) RENAL replacement therapy study investigators. N Engl J Med 361:1627–1638CrossRefPubMed
9.
Zurück zum Zitat Reffelmann T, Kloner RA (2009) Phosphodiesterase 5 inhibitors: are they cardioprotective? Cardiovasc Res 83:204–212CrossRefPubMed Reffelmann T, Kloner RA (2009) Phosphodiesterase 5 inhibitors: are they cardioprotective? Cardiovasc Res 83:204–212CrossRefPubMed
10.
Zurück zum Zitat Rosano GM, Aversa A, Vitale C (2005) Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 47:214–222CrossRefPubMed Rosano GM, Aversa A, Vitale C (2005) Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 47:214–222CrossRefPubMed
11.
Zurück zum Zitat Sohotnik R, Nativ O, Abbasi A et al (2013) Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1. Am J Physiol Renal Physiol 15(304):F1099–F1104CrossRef Sohotnik R, Nativ O, Abbasi A et al (2013) Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1. Am J Physiol Renal Physiol 15(304):F1099–F1104CrossRef
12.
Zurück zum Zitat Guzeloglu M, Yalcinkaya F, Atmaca S et al (2011) The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 86:197–203CrossRefPubMed Guzeloglu M, Yalcinkaya F, Atmaca S et al (2011) The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 86:197–203CrossRefPubMed
13.
Zurück zum Zitat Patel NN, Lin H, Toth T et al (2011) Phosphodiesterase-5 inhibition prevents postcardiopulmonary bypass acute kidney injury in swine. Ann Thorac Surg 92:2168–2176CrossRefPubMed Patel NN, Lin H, Toth T et al (2011) Phosphodiesterase-5 inhibition prevents postcardiopulmonary bypass acute kidney injury in swine. Ann Thorac Surg 92:2168–2176CrossRefPubMed
15.
Zurück zum Zitat Moran SMMB (1985) Course of acute renal failure studied by a model of creatinine kinetics. Kidney Int 27:937–982CrossRef Moran SMMB (1985) Course of acute renal failure studied by a model of creatinine kinetics. Kidney Int 27:937–982CrossRef
16.
Zurück zum Zitat Mishra J, Ma Q, Prada A et al (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543CrossRefPubMed Mishra J, Ma Q, Prada A et al (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543CrossRefPubMed
17.
Zurück zum Zitat Abassi Z, Shalabi A, Sohotnik R et al (2013) Urinary NGAL and KIM-1: biomarkers for assessment of acute ischemic kidney injury following nephron sparing surgery. J Urol 189(4):1559–1566CrossRefPubMed Abassi Z, Shalabi A, Sohotnik R et al (2013) Urinary NGAL and KIM-1: biomarkers for assessment of acute ischemic kidney injury following nephron sparing surgery. J Urol 189(4):1559–1566CrossRefPubMed
18.
Zurück zum Zitat Hidas G, Kastin A, Mullerad M et al (2006) Sutureless nephron-sparing surgery: use of albumin gluteraldehyde tissue adhesive. Urology 67:697–700CrossRefPubMed Hidas G, Kastin A, Mullerad M et al (2006) Sutureless nephron-sparing surgery: use of albumin gluteraldehyde tissue adhesive. Urology 67:697–700CrossRefPubMed
19.
Zurück zum Zitat Gill IS, Kamoi K, Aron M et al (2010) 800 laparoscopic partial nephrectomies: a single surgeon series. J Urol 183:34–41CrossRefPubMed Gill IS, Kamoi K, Aron M et al (2010) 800 laparoscopic partial nephrectomies: a single surgeon series. J Urol 183:34–41CrossRefPubMed
20.
Zurück zum Zitat Huang WC, Levey AS, Serio AM et al (2006) Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol 7:735–740PubMedCentralCrossRefPubMed Huang WC, Levey AS, Serio AM et al (2006) Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol 7:735–740PubMedCentralCrossRefPubMed
21.
Zurück zum Zitat Lane BR, Babineau DC, Poggio ED et al (2008) Factors predicting renal functional outcome after partial nephrectomy. J Urol 180:2363–2369CrossRefPubMed Lane BR, Babineau DC, Poggio ED et al (2008) Factors predicting renal functional outcome after partial nephrectomy. J Urol 180:2363–2369CrossRefPubMed
22.
Zurück zum Zitat Sandner P, Hütter J, Tinel H et al (2007) PDE5 inhibitors beyond erectile dysfunction. Int J Impot Res 19:533–543CrossRefPubMed Sandner P, Hütter J, Tinel H et al (2007) PDE5 inhibitors beyond erectile dysfunction. Int J Impot Res 19:533–543CrossRefPubMed
23.
Zurück zum Zitat Devarajan P (2010) Neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology 15:419–428CrossRefPubMed Devarajan P (2010) Neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology 15:419–428CrossRefPubMed
24.
Zurück zum Zitat Mishra J, Dent C, Tarabishi R et al (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed Mishra J, Dent C, Tarabishi R et al (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed
25.
Zurück zum Zitat Hosgood SA, Randle LV, Patel M et al (2014) Sildenafil citrate in a donation after circulatory death experimental model of renal ischemia-reperfusion injury. Transplantation 98(6):612–617CrossRefPubMed Hosgood SA, Randle LV, Patel M et al (2014) Sildenafil citrate in a donation after circulatory death experimental model of renal ischemia-reperfusion injury. Transplantation 98(6):612–617CrossRefPubMed
26.
Zurück zum Zitat Sesti C, Florio V, Johnson EG, Kloner RA (2007) The phosphodiesterase-5 inhibitor tadalafil reduces myocardial infarct size. Int J Impot Res 19:55–61CrossRefPubMed Sesti C, Florio V, Johnson EG, Kloner RA (2007) The phosphodiesterase-5 inhibitor tadalafil reduces myocardial infarct size. Int J Impot Res 19:55–61CrossRefPubMed
27.
Zurück zum Zitat Lin CS (2004) Tissue expression, distribution, and regulation of PDE5. Int J Impot Res 16(Suppl 1):S8–S10CrossRefPubMed Lin CS (2004) Tissue expression, distribution, and regulation of PDE5. Int J Impot Res 16(Suppl 1):S8–S10CrossRefPubMed
28.
Zurück zum Zitat Abu-Saleh N, Ovcharenko E, Awad H et al (2012) Involvement of the endothelin and nitric oxide systems in the pathogenesis of renal ischemic damage in an experimental diabetic model. Life Sci 91:669–675CrossRefPubMed Abu-Saleh N, Ovcharenko E, Awad H et al (2012) Involvement of the endothelin and nitric oxide systems in the pathogenesis of renal ischemic damage in an experimental diabetic model. Life Sci 91:669–675CrossRefPubMed
29.
Zurück zum Zitat Choi DE, Jeong JY, Lim BJ et al (2009) Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol 297:F362–F370CrossRefPubMed Choi DE, Jeong JY, Lim BJ et al (2009) Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol 297:F362–F370CrossRefPubMed
30.
Zurück zum Zitat Das A, Xi L, Kukreja RC (2005) Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem 280:12944–12955CrossRefPubMed Das A, Xi L, Kukreja RC (2005) Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem 280:12944–12955CrossRefPubMed
31.
Zurück zum Zitat Dai W, Kloner RA (2012) Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure? Circulation 125:1341–1343CrossRefPubMed Dai W, Kloner RA (2012) Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure? Circulation 125:1341–1343CrossRefPubMed
33.
Zurück zum Zitat Whitaker RM, Wills LP, Stallons LJ et al (2013) cGMP-selective phosphodiesterase inhibitors stimulate mitochondrial biogenesis and promote recovery from acute kidney injury. J Pharmacol Exp Ther 347:626–634PubMedCentralCrossRefPubMed Whitaker RM, Wills LP, Stallons LJ et al (2013) cGMP-selective phosphodiesterase inhibitors stimulate mitochondrial biogenesis and promote recovery from acute kidney injury. J Pharmacol Exp Ther 347:626–634PubMedCentralCrossRefPubMed
34.
Zurück zum Zitat Sabbisetti VS, Waikar SS, Antoine DJ et al (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol 25:2177–2186PubMedCentralCrossRefPubMed Sabbisetti VS, Waikar SS, Antoine DJ et al (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol 25:2177–2186PubMedCentralCrossRefPubMed
Metadaten
Titel
Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1
verfasst von
Yousef Lahoud
Osamah Hussein
Amjad Shalabi
Omri Nativ
Hoda Awad
Mogher Khamaisi
Ibrahim Matar
Ofer Nativ
Zaid Abassi
Publikationsdatum
01.12.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 12/2015
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-015-1579-3

Weitere Artikel der Ausgabe 12/2015

World Journal of Urology 12/2015 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

Stufenschema weist Prostatakarzinom zuverlässig nach

22.04.2024 Prostatakarzinom Nachrichten

Erst PSA-Test, dann Kallikrein-Score, schließlich MRT und Biopsie – ein vierstufiges Screening-Schema kann die Zahl der unnötigen Prostatabiopsien erheblich reduzieren: Die Hälfte der Männer, die in einer finnischen Studie eine Biopsie benötigten, hatte einen hochgradigen Tumor.

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

20.04.2024 EAU 2024 Kongressbericht

Beim chronischen Harnwegsinfekt bei Frauen wird bisher meist eine Antibiotikaprophylaxe eingesetzt. Angesichts der zunehmenden Antibiotikaresistenz erweist sich das Antiseptikum Methenamin-Hippurat als vielversprechende Alternative, so die Auswertung einer randomisierten kontrollierten Studie.

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.