Na-K/2Cl transporter inhibition for reduction of postischemic kidney failure tested in autologous reperfusion

  • R. Prestel
  • M. Storck
  • R. Pooth
  • G. Steinbach
  • C. Hammer
  • D. Abendroth
Conference paper


Postischemic kidney function may be influenced by donor conditioning. The sulfamoylbenzoate “piretanide” (P) is a diuretic agent with an inhibitory effect on the luminal Na-K-2CL-transporter system in the ascending part of the loop of Henle. A clinical pilot study demonstrated a lower rate of organ dysfunction following transplantation in humans when the donor organs were pretreated with piretanide. In an experimental ex vivo model the effect of piretanide on immediate organ function following long or short cold ischemia was studied. Porcine kidneys (n = 36) were removed after in situ transaortal hypothermic flushing with 21 Eurocollins solution. Following short storage (1 h, n = 18) or long storage (24 h, n = 18) the kidneys were reperfused with intraoperatively drawn heparinized autologous blood diluted with Ringer's lactate to a hematocrit of 25%. Urine flow was higher in the piretanide-pretreated group (p), especially after long storage. The electrolyte loss was comparable in both groups. Postischemic endogenous creatinine clearance was significantly elevated in the treatment group (4.45 ± 0.6 ml/min per 100 mg in P vs 1.91 ± 0.4 ml/min per 100 mg, in control, P < 0.05 Mann-Whitney test). Renal hemodynamics were improved by piretanide, resulting in significantly lower resistance and allowing higher flow during pressurecontrolled perfusion. O2 consumption, representing general metabolic activity, was higher after long storage, indicating an earlier recovery from cold ischemia. In this ex vivo model, autologous reperfusion of porcine kidneys could be improved by piretanide pretreatment. Autoregulation of kidney vasculature was maintained as well as functional parameters such as creatinine clearance or gluconeogenesis. Therefore, piretanide may be used in larger clinical trials to further improve organ quality in times of donor shortage.

Key words

Piretanide Kidney transplantation Donor conditioning Ex vivo hemoperfusion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abendroth D, Pooth R, Schneeberger H, Land W (1993) Effects of piretanide on early graft function in kidney transplantation — a pilot study. Transplant Proc 25: 2626 - 2627Google Scholar
  2. 2.
    Booster M, Yin M, Kurvers HAJM, et al (1995) Inhibition of CD18-dependent leukocyte adherence by mAb 6.5 E does not prevent ischemia-reperfusion injury as seen in grafted kidneys. Transplant Int 8: 126 - 132Google Scholar
  3. 3.
    Clissold SP, Brogden RN (1985) Piretanide — a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drug 29: 489 - 530CrossRefGoogle Scholar
  4. 4.
    Göttl KH, Roesch A, Klinke R (1985) Quantitative evaluation of ototoxic side effects of furosemide, piretanide, bumetanide, azosemide and ozolinone in the cat — a new approach to the problem of ototoxicity. Naunyn Schmiedeberg's Arch Pharmacol 331: 275 - 282PubMedCrossRefGoogle Scholar
  5. 5.
    Hammer C (1994) Nature's obstacles to xenotransplantation. Transplant Rev 8: 174 - 184CrossRefGoogle Scholar
  6. 6.
    Kallerhoff M, Blech M, Kehrer G, et al (1987) Kidney function parameters after ischemic stress under Euro-collins or under HTK protection according to Bretschneider. Urologe 26: 96 - 103PubMedGoogle Scholar
  7. 7.
    Kaplan MP, Toledo-Pereya LH, Pietro-ski R, et al (1986) Transplant Proc 18: 504 - 505Google Scholar
  8. 8.
    Kirsten R, Alexandridis T, Heintz B, et al (1987) Elsevier 365-368Google Scholar
  9. 9.
    Klaus E, Alpermann MG, Caspritz G, Linz W, Scholkens B (1983) Vascular effects of piretanide. Studies on extra-renal action in several animal models. Arzneim Forsch 33: 1273-1276Google Scholar
  10. 10.
    Lawrence JR, Ansari AF, Elliot HL, et al (1978) Kinetic and dynamic comparison of piretanide and furosemide. Clin Pharmacol Ther 23: 558 - 565PubMedGoogle Scholar
  11. 11.
    Marone C, Reubi FC, Lahn W (1984) Comparison of the short-term effects of the loop diuretic piretanide and furosemide in patients with renal insufficiency. Eur J Clin Pharmacol 26: 413418Google Scholar
  12. 12.
    Rocher LL, Landers C, Dafoe DC, et al (1987) The importance of prolonged post-transplant dialysis requirement in cyclosporine-treated renal allograft recipients. Clin Transplant 1: 29 - 36Google Scholar
  13. 13.
    Ross BD, Espinal J, Silva P (1986) Glucose metabolism in renal tubular function. Kidney Int 29: 54 - 67PubMedCrossRefGoogle Scholar
  14. 14.
    Schneeberger H, Schleibner S, Schilling M, et al (1990) Prevention of acute renal failure after kidney transplantation by treatment with rh-SOD: interim analysis of a double-blind placebo controlled trial. Trnasplant Proc 22: 2224–2225Google Scholar
  15. 15.
    Storck M, Sirsjö A, Abendroth D, Hammer C (1995) Laser perfusion imaging (LPI) — a new method of monitoring microcirculation in postischemic organ reperfusion. (submitted)Google Scholar
  16. 16.
    Storck M, Schilling M, Steinbach G, Abendroth D Influence of systemic cyclooxygenase inhibition with single dose aspisol (ASA) on kinetics of arachidonic acid metabolism in the venous effluate of transplanted kidney grafts in humans. Transplant Proc (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • R. Prestel
    • 1
  • M. Storck
    • 2
  • R. Pooth
    • 2
  • G. Steinbach
    • 3
  • C. Hammer
    • 1
  • D. Abendroth
    • 2
  1. 1.Institute for Surgical ResearchLM University MunichGermany
  2. 2.Department of Surgery IIUniversity of UlmUlmGermany
  3. 3.Institute for Clinical ChemistryUniversity of UlmUlmGermany

Personalised recommendations