Arthritis und Rheuma 2007; 27(06): 335-339
DOI: 10.1055/s-0037-1619727
Aktuelle Aspekte der Osteologie
Schattauer GmbH

Bisphosphonate und Niere

Bisphosphonates and kidney
R. Bergner
1   Medizinische Klinik A, Klinikum der Stadt Ludwigshafen
› Author Affiliations
Further Information

Publication History

Publication Date:
24 December 2017 (online)

Zusammenfassung

Bisphosphonate sind heute fester Bestandteil derTherapie bei verschiedenen Knochenerkrankungen. Nach der Aufnahme in den Blutkreislauf werden sie entweder in den Knochen aufgenommen oder unmetabolisiert renal ausgeschieden. Hierbei wird auch bei jeder I nfusion ein geringer Teil in den Tubuluszellen abgelagert. Dies kann bei Kumulation zu einem teilweise irreversiblen Nierenversagen führen. Bei eingeschränkter Nierenfunktion ist die Bisphosphonatausscheidung reduziert, so dass bei den verschiedenen Bisphosphonaten in unterschiedlichem Maß die Dosis reduziert werden muss. Teilweise sind bestimmte Bisphosphonate bei schwer eingeschränkter Nierenfunktion sogar kontraindiziert. Dies gilt vor allem für den Indikationsbereich der Onkologie. Bei osteologischen Indikationen wird die Bisphosphonatgabe allgemein wegen fehlender Daten bei einer schwer eingeschränkten Nierenfunktion nicht mehr empfohlen. Bei dringender Indikation können hier jedoch die Dosisempfehlungen in der Onkologie weiterhelfen.

Summary

Bisphosphonatesare today’sstandard treatmentin different diseases ofthe bone. After their uptake by the blood circulation they are well absorbed by the bone or eliminated unmetabolized by the kidney. A small amount of the substance will be retained and deposited in cells ofthe proximal tubule. Acute and sometimes irreversible renal failure occurs if the bisphosphonates accumulate in the kidney. Renal excretion of bisphosphonates is reduced in renal insufficiency. This means that the dosage of different bisphosphonates has to be adapted accordingly. In severe renal insufficiency some bisphosphonates may not be indi- cated.This holds true especially for the field of oncological indications. In osteological ailments most bisphosphonates are even contraindicated in severe renal insufficiency. On the other hand, dosis recommendations taken from oncology may be helpful if treatment is needed in patients with osteoporosis and with severe renal failure.

 
  • Literatur

  • 1 Ala-Houhala I, Saha H, Liukko-Sipi S. et al. Pharmacokinetics of clodronate in haemodialysis patients. Nephrol Dial Transplant 1999; 14: 699-705.
  • 2 Barri YM, Munshi NC, Sukumalchantra S. et al. Podocyte injury associated glomerulopathies induced by pamidronate. Kidney Int 2004; 65: 634-641.
  • 3 Banerjee D, Asif A, Striker L. et al. Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis 2003; 41: E18.
  • 4 Beigel AE, Rienhoff E, Olbricht CJ. Removal of clodronate by haemodialysis in end-stage renal disease patients. Nephrol Dial Transplant 1995; 10: 2266-2268.
  • 5 Berenson JR, Rosen L, Vescio R. et al. Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function. J Clin Pharmacol 1997; 37: 285-290.
  • 6 Bergner R, Dill K, Boerner D, Uppenkamp M. Elimination of intravenously administered ibandronate in patients on haemodialysis: a monocentre open study. Nephrol Dial Transplant 2002; 17: 1281-1285.
  • 7 Bergner R, Henrich DM, Hoffmann M. et al. Renal safty and pharmakokinetics of ibandronate in multiple myeloma patients with or without impaired renal function. J Clin Pharmacol 2007; 47: 942-950.
  • 8 Breuil V, Euller-Ziegler L. Bisphosphonate therapy in rheumatoid arthritis. Joint Bone Spine 2006; 73: 349-354.
  • 9 Buttazzoni M, Rosa Diez GJ, Jager V. et al. Elimination and clearance of pamidronate by haemodialysis. Nephrology 2006; 11 (03) 2-197.
  • 10 Cal JC, Daley-Yates PT. Disposition and nephrotoxicity of 3-amino-1-hydroxyproylidene-1,1-bisphosphonate (APD), in rats and mice. Toxicology 1990; 65: 179-197.
  • 11 CDER New and Generic Drug Approval 1998-2003: Boniva (ibandronate sodium) Tablets, NDA21-455,. Pharmacology Review Part 2, Pharmacokinetics/Toxicokinetics,. http://www.fda.gov/cder/foi/nda/2003/21-455_Boniva_pharmr_P2.pdf
  • 12 CDER New and Generic Drug Approval 1998-2003: Zometa (zoledronic acid) Injection, NDA 21-223,. Pharmacological Review Part 2; Pharmacokinteics Summary,. http://www.fda.gov/cder/foi/nda/2001/21-223_Zormeta_pharmr_P2.pdf
  • 13 Chang JT, Green L, Beitz J. Renal failure with the use of zolendronic acid. New Engl J Med 2003; 349 (17) 2-1676.
  • 14 Desikan R, Veksler Y, Raza S. et al. Nephroticproteinuria associated with high-dose pamidronate in multiple myeloma. Br J Haematol 2002; 119: 496-499.
  • 15 Eggelmeijer F, Papapoulos SE, van Paassen HC. et al. Clinical and biochemical response to single infusion of pamidronate in patients with active rheumatoid arthritis: a double blind placebo controlled study. J Rheumatol 1994; 21: 2016-2020.
  • 16 Jarrett SJ, Conaghan PG, Sloan VS. et al. Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in early rheumatoid arthritis. Arthritis Rheum 2006; 54: 1410-1414.
  • 17 Johnson K, Gable P, Kaime EM. et al. Significant deteriortion in renal function with the new bisphosphonate, zoledronic acid. Proc Am Soc Clin Oncol 2003; 22: 738 (abstract 2968).
  • 18 Kino I, Kato Y, Lin JH, Sugiyama Y. Renal handling of bisphosphonate alendronate in rats. Biopharm Drug Dispos 1999; 20: 193-198.
  • 19 Kunin M, Kopolovic J, Avigdor A, Holtzman EJ. Collapsing glomerulopathy induced by long-term treatment with standard-dose pamidronate in a myeloma patient. Nephrol Dial Transplant 2004; 19: 723-726.
  • 20 Lin JH, Duggan DE, Chen I. Ellsworth RL. Physiological disposition of alendronate, a potent antiosteolytic bisphosphonate, in laboratory animals. Drug Metab Dispos 1991; 19: 926-932.
  • 21 Lin JH, Chen I, Deluna FA, Hichens M. Renal handling of alendronate in rats - an uncharacterized renal transport system. Drug Metab Dispos 1992; 20: 608-613.
  • 22 Lockridge L, Lockridge L, Papac RJ, Perazella MA. Pamidronate-associated nephrotoxicity in a patient with Langerhans’s histiocytosis. Am J Kidney Dis 2002; 40: E2.
  • 23 Markowitz GS, Appel GB, Fine PL. et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 2001; 12: 1164-1172.
  • 24 Markowitz GS, Fine PL, Stack JI. et al. Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 2000; 64: 281-289.
  • 25 Mazzantini M, Di Munno O, Metelli MR. et al. Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patients with active rheumatoid arthritis: effects on disease activity and bone resorption markers. Aging Clin Exp Res 2002; 14: 197-201.
  • 26 Mönkkönen J, Ylitalo P, Elo HA, Airaksinen MM. Distribution of (14C)Clodronate (Dichloromethylene Bisphosphonate) disodium in mice. Toxicol Appl Pharmacol 1987; 89: 287-92.
  • 27 Romas E. Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 2005; 19: 1065-1079.
  • 28 Skerjanec A, Berenson J, Hsu C. et al. The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function. J Clin Pharmacol 2003; 43: 154-162.
  • 29 Smetana S, Michlin A, Rosenman E. et al. Pamidronate-induced nephrotoxic tubular necrosis-a case report. Clin Nephrol 2004; 61 (01) 2-63.
  • 30 Stein SH, Davidson R, Tweed A. et al. Renal dysfunction with iv bisphosphonates in patients with metastatic breast cancer. Proc Am Soc Clin Oncol 2003; 22 (abstract 2997): 745.
  • 31 Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis (In Process Citation). Drug Saf 2007; 30: 755-763.
  • 32 Ullrich KJ, Rumrich G, Burke TR. et al. Interaction of Alkyl/Arylphosphonates, phosphonocarboxylates and diphosphonates with different anion transport systems in the proximal renal tubule. J Pharmacol Exp Ther 1997; 283 (03) 1-1223.
  • 33 Valleala H, Teronen O, Friman C. et al. Inhibition of collagenase by a bisphosphonate-group drug in patients with rheumatoid arthritis. J Rheumatol 2000; 27: 1570-1572.
  • 34 Yanik B, Bavbek N, Yanik T. et al. The effect o alendronate, risedronate and raloxifene on renal functions based on Cockcroft and Gaultmethod in postmenopausal women. Ren Fail 2007; 29: 471-476.