Agents and Actions

, Volume 5, Issue 4, pp 322–325 | Cite as

Anti-inflammatory drugs and renal papillary necrosis

  • Edward H. Wiseman
  • Harald Reinert
Immunosuppression and Inflammation Mini-Review


The literature on renal papillary necrosis (RPN) associated with the administration of non-steroidal antiinflammatory drugs (NSAID) to rats and man, is reviewed. RPN is almost universally reported after long term administration of NSAID to rats, reports being cited for an indomethacin analog, phenylbutazone, fenamic acids, fenoprofen and sudoxicam. Aspirin will also induce RPN in rats, and is probably the cause of the ‘analgesic nephropathy’ linked to abuse of aspirin/phenacetin combinations in man. RPN is reported at autopsy in human arthritics, but whether this is a facet of the disease, or of long term salicylate ingestion, is not clear. NSAID are rarely implicated in RPN in humans.


Aspirin Indomethacin Salicylate Phenylbutazone Term Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    D.M. Brown andT.L. Hardy,Short-Term Study of the Effect of Phenactin, Phenazone and Amidopyrine on the Rat Kidney, Br. J. Pharmac. Chemother.32, 17–24 (1968).Google Scholar
  2. [2]
    P. Kincaid-Smith,Analgesic Nephropathy, Br. Med. J.4, 618 (1970).Google Scholar
  3. [3]
    D.H. Kaump,Pharmacology of the Fenamates. II. Toxicology in Animals, Ann. Phys. Med.9, 16–23 (1966).Google Scholar
  4. [4]
    Mefenamic Acid (Ponstel) Package Insert, in:Physician's Desk Reference (Medical Economics, Oradell, N.J. 1975), p. 1141.Google Scholar
  5. [5]
    R.S. Nanra, P. Chirawong andP. Kincaid-Smith,Renal Papillary Necrosis in Rats Produced by Aspirin, A.P.C. and other Analgesics, in:Renal Infection and Renal Scarring (Eds P. Kincaid-Smith and K.F. Fairley; Mercedes, Melbourne 1971), p. 347.Google Scholar
  6. [6]
    T.L. Hardy,N-Phenyl Anthranilic Acid: An Agent for Inducing and Studying Renal Papillary Necrosis in the Rat, Br. J. exp. Path.51, 348–355 (1970).Google Scholar
  7. [7]
    J.L. Emmerson, W.R. Gibson, E.C. Pierce andG.F. Kiplinger,Preclinical Toxicology of Fenoprofen, Toxic. appl. Pharmac.25, 444 (1973).Google Scholar
  8. [8]
    J.R. Ward andR.S. Cloud,Comparative Effect of Anti-Rheumatic Drugs on Adjuvant-Induced Polyarthritis in Rats, J. Pharmac. exp. Ther.152, 116–121 (1966).Google Scholar
  9. [9]
    L. Arnold, C. Collins andG.A. Starmer,Renal and Gastric Lesions after Phenylbutazone and Indomethacin in the Rat, Pathology6, 303–313 (1974).PubMedGoogle Scholar
  10. [10]
    D.L. Bokelman, W.J. Bagdon, P.A. Mattis andP.F. Stonier,Strain-Dependent Renal Toxicity of a Nonsteroid Anti-Inflammatory Agent, Toxic. appl. Pharmac.19, 111–124 (1971).Google Scholar
  11. [11]
    O. Olafsson, K.R. Gudmundsson andA. Brekkan,Migraine, Gastritis and Renal Papillary Necrosis. A Syndrome in Chronic Non-Obstructive Pyelonephritis, Acta med. scand.179, 121–128 (1966).PubMedGoogle Scholar
  12. [12]
    L.R. Prescott,Phenacetin Nephropathy, Br. Med. J.4, 493 (1970).Google Scholar
  13. [13]
    D.H. Lawson,Analgesic Consumption and Impaired Renal Function, J. Chron. Dis.26, 39–45 (1973).PubMedGoogle Scholar
  14. [14]
    J.A. Abel,Analgesic Nephropathy — a Review of the Literature, 1967–1970, Clin. Pharmac. Ther.12, 583–598 (1971).Google Scholar
  15. [15]
    D.P.E. Kingsley, B. Goldberg, C. Abrahams, A.J. Meyers, K.I. Furman andI. Cohen,Analgesic Nephropathy, Br. Med. J.4, 656–659 (1972).PubMedGoogle Scholar
  16. [16]
    R.M. Murray,The Origins of Analgesic Nephropathy, Br. J. Psychiat.123, 99–106 (1973).Google Scholar
  17. [17]
    R.J. Bulger, L.A. Healey andP. Polinsky,Renal Abnormalities in Rheumatoid Arthritis, Ann. Rheum. Dis.27, 339–343 (1968).PubMedGoogle Scholar
  18. [18]
    H.C. Burry,Renal Disorders in Rheumatoid Arthritis, Rheum. Phys. Med.11, 2–9 (1971).Google Scholar
  19. [19]
    R.D. Wigley,Aspirin and the Kidney, N.Z. Med. J.74, 301–305 (1971).PubMedGoogle Scholar
  20. [20]
    R.S. Nanra, J.D. Hicks, J.H. McNamara andP. Kincaid-Smith,Seasonal Variatio in the Postmortem Incidence of Renal Papillary Necrosis, Med. J. Aust.1, 293–296 (1970).Google Scholar
  21. [21]
    A. Morales andJ. Steyn,Papillary Necrosis Following Phenylbutazone Ingestion, Arch. Surg.103, 420–421 (1971).PubMedGoogle Scholar
  22. [22]
    A.J.R. Clarkson andJ.R. Lawrence,The Clinical Features of Analgesic Nephropathy, in:Renal Infection and Renal Scarring (Eds P. Kincaid-Smith and K.F. Fairley: Mercedes, Melbourne 1971), p. 375.Google Scholar
  23. [23]
    J.K. Dawborn, I.F. Fairley, P. Kincaid-Smith andW.E. King,The Association of Peptic Ulceration, Chronic Renal Failure and Analgesic Abuse, Q. J. Med.35, 69–83 (1966).PubMedGoogle Scholar
  24. [24]
    S.K. Fellner andE.P. Tuttle,The Clinical Syndrome of Analgesic Abuse, Arch. int. Med.124, 379–382 (1969).Google Scholar
  25. [25]
    M.H. Gault, T.C. Rudwal, W. Engles andB. Dossetor,Syndrome Associated with the Abuse of Analgesics, Ann. int. Med.68, 906–923 (1968).PubMedGoogle Scholar
  26. [26]
    K. Grimlund,Renal Papillary Necrosis at a Swedish Factory, Acta med. scand.174 (Suppl. 405), 1–26 (1963).Google Scholar
  27. [27]
    O. Gsell, U.C. Dubach andU. Raillard-Peucker,Phenacetinabusus und Nierenleiden, Dt. Med. Wschr.93, 101–108 (1968).Google Scholar
  28. [28]
    B. Harvald,Renal Papillary Necrosis. A Clinical Survey of 66 Cases, Am. J. Med.35, 69–83 (1963).Google Scholar
  29. [29]
    P. Kincaid-Smith,Analgesic Nephropathy — a Common Cause of Renal Disease in Australia, Med. J. Aust.2, 1131–1135 (1969).PubMedGoogle Scholar
  30. [30]
    U.C. Dubach, P.S. Levy andA. Müller,Relationship between Regular Analgesic Intake and Urorenal Disorders in a Working Female Population of Switzerland. I. Initial Studies (1968), Am. J. Epidemiol.93, 425–434 (1971).PubMedGoogle Scholar
  31. [31]
    O. Spuhler andH.O. Zollinger,Die chronische interstitielle Nephritis, Z. Klin. Med.151, 1–50 (1953).PubMedGoogle Scholar
  32. [32]
    A.L. Linton,Renal Disease Due to Analgesics. I. Recognition of the Problem of Analgesic Nephropathy, Can. med. Ass. J.107, 749–751 (1972).PubMedGoogle Scholar
  33. [33]
    D.R. Wilson,Renal Disease Due to Analgesics. II. Analgesic Nephropathy in Canada: a Retrospective Study of 351 Cases, Can. med. Ass. J.107, 752–755 (1972).PubMedGoogle Scholar
  34. [34]
    M.H. Gault,Renal Disease Due to Analgesics. III. Evidence for the Nephrotoxicity of Analgesics, Can. med. Ass. J.107, 756–758 (1972).PubMedGoogle Scholar
  35. [35]
    T. Murray andM. Goldberg,Analgesic Abuse and Renal Disease, Ann. Rev. Med.26, 537–550 (1975).PubMedGoogle Scholar
  36. [36]
    R.S. Nanra andP. Kincaid-Smith,Popillary Necrosis in Rats Caused by Aspirin and Aspirin-Containing Mixtures, Br. Med. J.3, 559–561 (1970).PubMedGoogle Scholar
  37. [37]
    G. Woodard, K.F. Post, K.O. Cockrell andM.T.I. Cronin,Phenacetin: Long Term Studies in Rats and Dogs, Toxic. appl. Pharmac.7, 503 (1965).Google Scholar
  38. [38]
    E. Clausen,Histological Changes in Rabbit Kidneys Induced by Phenacetin and Acetylsalicyclic Acid, Lancet, p. 123–124 (1964).Google Scholar
  39. [39]
    M.H. Gault, J. Blennerhasset andR.C. Muehrcke,Analgesic Nephropathy. A Clinicopathologic Study Using Electron Microscopy, Am. J. Med.51, 740–756 (1971).PubMedGoogle Scholar
  40. [40]
    E. Levine andD. Bernard,Analgesic Nephropathy. A Clinico-Radiological Study, S. African Med. J.47, 2439–2443 (1973).Google Scholar
  41. [41]
    T.W. Steele, A.Z. Györy andK.D.G. Edwards,Renal Function in Analgesic Nephropathy, Br. Med. J.2, 213–216 (1969).PubMedGoogle Scholar
  42. [42]
    P. Miescher, U. Schnyder andU. Krech,Zur Pathogenese der «interstitiellen Nephritis→ bei Abusus phenactinhaltiger Analgetica. Tierexperimentelle Untersuchungen, Schweiz. Med. Wschr.88, 432–437 (1958).PubMedGoogle Scholar
  43. [43]
    A. Studer, G. Zbinden andB. Fust,Weitere tierexperimentelle Untersuchungen zur Frage Schmerzmittelmissbrauch und interstitielle Nephritis, Schweiz. Med. Wschr.88, 469–470 (1958).PubMedGoogle Scholar
  44. [44]
    P. Kincaid-Smith, R.S. Nanra andK.F. Fairley,Analgesic Nephropathy: a Recoverable Form of Chronic Renal Failure, in:Renal Infection and Renal Scarring (Eds P. Kincaid-Smith and K.F. Fairley; Mercedes, Melbourne 1971), p. 385.Google Scholar
  45. [45]
    R.A. Axelsen andA.F. Burry,Analgesics and the Kidney, Br. Med. J.5, 784–785 (1973).Google Scholar
  46. [46]
    E.H. Wiseman andJ. Chiaini,Anti-Inflammatory and Pharmacokinetic Properties of Sudoxicam, N-(2-Thiazolyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, Biochem. Pharmac.21, 2323–2334 (1972).Google Scholar
  47. [47]
    R. Rau andD. Gross,Therapy of Rheumatoid Arthritis with Sudoxicam, Abstr. XIIIth Int. Cong. Rheum., # 396 (October 1973).Google Scholar
  48. [48]
    S.H. Roth, D.W. Englund andB.K. Harris,Preliminary Evaluation of Sudoxicam in Rheumatoid Arthritis, Abstr. XIIIth Int. Cong. Rheum., #397 (October 1973).Google Scholar
  49. [49]
    D.C. Hobbs,Metabolism of Sudoxicam in Experimental Animals and Man, Pharmacologist17, 268 (1975).Google Scholar

Copyright information

© Birkhäuser-Verlag 1975

Authors and Affiliations

  • Edward H. Wiseman
    • 1
    • 2
  • Harald Reinert
    • 1
    • 2
  1. 1.Department of PharmacologyPfizer Central ResearchGrotonUSA
  2. 2.Research CenterAmboiseFrance

Personalised recommendations