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Saluretic effect of the loop diuretic torasemide in chronic renal failure

Interdependence of electrolyte excretion

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Summary

The effects of torasemide have been studied in 7 healthy controls and 9 patients with stable chronic renal failure of various degrees.

After a control period of 3 days torasemide 20 mg i. v. caused a dramatic increase in diuresis and electrolyte excretion without affecting the glomerular filtration rate. The duration of action of torasemide, τ, averaged 6 h and was independent of the creatinine clearance, CLCR. When related to τ the drug-induced excretion of Cl−, Na+, K+, Ca2+ and Mg2+ showed strong linear dependence on CLCR. Both the kaliuresis and the calciuresis during τ were tightly correlated with the natriuresis over the broad range of CLCR. Similarly, the excretion of Mg2+ was dependent on the kaliuresis.

The torasemide-induced kaliuresis amounted to 12% of natriuresis, as after furosemide. The kaliuretic effect of loop diuretics is smaller than that of the thiazides. After τ, e. g. over a 24 h period, kaliuresis was not correlated with natriuresis. The magnitude of the rebound effect was diminished with increasing renal impairment.

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References

  1. Wittner M, Di Stefano A, Schlatter E, Delarge J, Greger G (1986) Torasemide inhibits NaCl reabsorption in the thick ascending limb of the loop of Henle. Pflügers Arch 407: 611–614

    Google Scholar 

  2. Delarge J, Lapière C (1974) Synthèse et propriétés pharmacologiques des quelques N-acylsulfonamides. Ann Pharm Fr 32: 657–667

    Google Scholar 

  3. Delarge J, Lapière C (1978) Une nouvelle classe de diurétiques “high ceiling”, dérivés de l'alkyl-1 (phenylamino-4-pyridyl-3-sulfonyl)-3 urée. Ann Pharm Fr 36: 369–380

    Google Scholar 

  4. Scheen AJ, Vancrombreucq JC, Delarge J, Luyckx AS (1986) Diuretic activity of torasemide and furosemide in chronic heart failure: A comparative double blind cross-over study. Eur J Clin Pharmacol 31 [Suppl]: 35–42

    Google Scholar 

  5. Spannbrucker N, Achhammer I, Metz P, Glocke M (1988) Comparative study on the antihypertensive efficacy of torasemide and indapamide in patients with essential hypertension. Arzneim-Forsch/Drug Res 38 (I): 190–193

    Google Scholar 

  6. Dodion L, Willems JL (1986) Study of the elimination kinetics of torasemide, a novel loop diuretic, in renal insufficiency. Eur J Clin Pharmacol 32 [Suppl]: 49–51

    Google Scholar 

  7. Klütsch K, Großwendt J, Haecker W (1988) Single dose comparison of torasemide and furosemide in patients with advanced renal failure. Arzneim-Forsch/Drug-Res 38 (I): 200–204

    Google Scholar 

  8. Breslau N, Moses AM, Weiner JM (1976) The role of volume contraction in the hypocalciuric action of chlorothiazide. Kidney Int 10: 164–170

    Google Scholar 

  9. Brater DC, Leinfelder J, Anderson SA (1987) Clinical pharmacology of torasemide, a new loop diuretic. Clin Pharmacol Ther 42: 187–192

    Google Scholar 

  10. Brater DC, Anderson SA, Brown-Cartwright D (1986) Response to furosemide in chronic renal insufficiency: Rationale for limited dose. Clin Pharmacol Ther 40: 134–139

    Google Scholar 

  11. Gerber JG (1981) Antihypertensive agents and diuretics. In: Anderson RJ, Schrier Rw (Eds) Clinical use of drugs in patients with kidney and liver disease. Saunders, London, pp 211–229

    Google Scholar 

  12. Keller E, Hoppe-Seyler G, Mumm R, Schollmeyer P (1981) Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide. Eur J Clin Pharmacol 20: 27–33

    Google Scholar 

  13. Knauf H, Mutschler E (1990) The Na load in the nephron segment determines the ceiling qualitiy of a diuretic. In: JB Puschett, editor. Diuretics III, Chemistry, Pharmacology and Clinical Applications. Elsevier, New York, pp 359–362

    Google Scholar 

  14. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodés J (1988) Peripheral arterial vasodilation hypothesis. A proposal for the initiation or renal sodium and water retention in cirrhosis. Hepatol 8: 1115–1157

    Google Scholar 

  15. Brater DC, Chennavasin P, Seiwell R (1980) Furosemide in patients with heart failure: Shift in dose-response curves. Clin Pharmacol Ther 28: 182–186

    Google Scholar 

  16. Keller E, Hoppe-Seyler G, Schollmeyer P (1982) Disposition and diuretic effect of furosemide in the nephrotic syndrome. Clin Pharmacol Ther 32: 442–449

    Google Scholar 

  17. Skorecki KL, Brenner BM (1982) Body fluid homeostasis in congestive heart failure and cirrhosis with ascites. Am J Med 72: 323–337

    Google Scholar 

  18. Epstein M (1988) Renal sodium handling in liver disease. In: Epstein M (editor). The kidney in liver disease, 3. ed. Williams and Wilkins, Baltimore, pp 3–30

    Google Scholar 

  19. Fine LG, Sakhrani LM (1983) Toward a physiological definition of the hepatorenal syndrome. In: Epstein M (editor). The kidney in liver disease, 3. ed. Williams and Wilkins, Baltimore, pp 107–111

    Google Scholar 

  20. Schrier RW (1988) Pathogenesis of sodium and water retention in high and low output cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. N Engl J Med 319: 1065–1072

    Google Scholar 

  21. Knauf H, Wenk E, Schölmerich J, Georg KJ, Gerok W, Leser HG, Mutschler E (1990) Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion. Klin Wochenschr, 68: 545–551

    Google Scholar 

  22. Bricker NS (1982) Sodium homeostasis in chronic renal disease. Kidney Int 21: 886–897

    Google Scholar 

  23. Lesne M, Clerckx-Braun F, Duhoux P, Van Ypersele de Strihou C (1982) Pharmacokinetic study of torasemide in humans: an overview of its diuretic effect. Int J Clin Pharmacol Ther Toxicol 20: 382–387

    Google Scholar 

  24. Neugebauer G, Besenfelder E, von Möllendorff E (1988) Pharmacokinetics and metabolism of torasemide in man. Arzneim-Forsch/Drug Res 38 (I): 164–166

    Google Scholar 

  25. Spahn H, Knauf H, Mutschler E (1990) Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure. Eur J Clin Pharmacol 39: 345–348

    Google Scholar 

  26. Knauf H, Liebig R, Schollmeyer P, Rosenthal J, Kölle EK, Mutschler E (1984) Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function. Eur J Pharmacol 26: 687–693

    Google Scholar 

  27. Thurau K (1977) Diuretics and tubuloglomerular feedback regulation of GFR. In: Siegenthaler W, Beckerhoff R, Wetter W (eds) Diuretics in research and clinics. Thieme, Stuttgart, pp 43–50

    Google Scholar 

  28. Schlatter E, Salomonsson M, Person AEG, Greger R (1990) Macula densa cells reabsorb NaCl via furosemide-sensitive Na+:K+:2Cl cotransport. In: Puschett JB (ed). Diuretics III, chemistry, pharmacology and clinical applications. Elsevier, New York, pp 756–758

    Google Scholar 

  29. Schnermann J, Briggs P (1985) Function of the juxtaglomerular apparatus: Local control of glomerular hemodynamics. In: Seldin D, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, pp 669–697

    Google Scholar 

  30. Greger R, Schlatter E (1983) Cellular mechanism of the action of loop diuretics on the thick ascending limb of Henle's loop. Klin Wochenschr 61: 1019–1027

    Google Scholar 

  31. Wright F, Giebisch G (1985) Regulation of potassium excretion. In: Seldin D, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, pp 1223–1249

    Google Scholar 

  32. Wright F (1986) Renal potassium transport along the nephron. In: Giebisch G (ed) Potassium transport: physiology and pathophysiology. Academic Press, New York

    Google Scholar 

  33. Knauf H, Reuter K, Mutschler E (1985) Limitation on the use of amiloride in early renal failure. Eur J Clin Pharmacol 28: 61–66

    Google Scholar 

  34. Constanzo LS, Windhager EE (1978) Calcium and sodium transport by the distal convoluted tubule of the rat. Am J Physiol 235: F492-F506

    Google Scholar 

  35. Suki WN (1979) Calcium transport in the nephron. Am J Pharmacol 237:F1-F6

    Google Scholar 

  36. Imai M (1978) Calcium transport across the rabbit thick ascending limb of Henle's loop perfused in vitro. Pflügers Arch 374: 255–263

    Google Scholar 

  37. Sutton RAL, Dirks JH (1975) The renal excretion of calcium: A review of micropuncture data. Can J Physiol Pharmacol 53: 979–988

    Google Scholar 

  38. Knauf H, Mutschler E (1984) Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function. Eur J Pharmacol 26: 513–520

    Google Scholar 

  39. Quamme GA, Dirks JH (1985) Magnesium: cellular and renal exchanges. In: Seldin DW, Giebisch G (eds) The kidney physiology and pathophysiology. Raven, New York, pp 1269–1280

    Google Scholar 

  40. Knauf H, Mutschler E, Pooth R (1990) Piretanide in mild and advanced renal failure: Pharmacodynamics and renal hemodynamics. In: Puschett JB (ed) Diuretics III, chemistry, pharmacology and clinical applications. Elsevier, New York, pp 346–349

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik I, St. Bernward-Krankenhaus, Hildesheim, FRG

    H. Knauf

  2. Pharmakologisches Institut für Naturwissenschaftler der Johann Wolfgang Goethe Universität, Frankfurt a/M, FRG

    E. Mutschler

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  1. H. Knauf
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  2. E. Mutschler
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In memory of our colleague and friend U. Wais who left us too early

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Knauf, H., Mutschler, E. Saluretic effect of the loop diuretic torasemide in chronic renal failure. Eur J Clin Pharmacol 39, 337–343 (1990). https://doi.org/10.1007/BF00315406

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  • DOI: https://doi.org/10.1007/BF00315406

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