Pediatric Nephrology

, Volume 1, Issue 4, pp 615–622 | Cite as

The inflammatory response and tissue damage

The example of renal scars following acute renal infection
  • M. P. Glauser
  • P. Meylan
  • J. Bille
Invited Review


Most clinical and experimental evidence suggests that renal scarring occurs following urinary tract infections in those patients with an abnormality of the urinary tract or kidney function. Experimentally, bacterial multiplication within the kidney occurs only in the presence of obstruction, leading rapidly to acute exudative pyelonephritis and invariably to kidney scars within weeks. Various manipulations of the bacterial load and/or of the inflammatory response during acute pyelonephritis have demonstrated that the inflammatory processes, not the bacterial component of pyelonephritis, are responsible for permanent renal tissue damage. Polymorphonuclear leucocytes (PMNLs) infiltrating the kidney tissue during acute pyelonephritis appear to release metabolites that are toxic to the parenchyma. Indeed, both the prevention of PMNL influx into renal tissue, by means of colchicine or cyclophosphamide, and the inactivation of some of their toxic metabolites, by means of dapsone, have led to the prevention of tissue damage and kidney scars. However, the most potent protective activity was observed with early antibiotic treatment, which stopped bacterial multiplication and prevented the early influx of PMNLs, thus preventing tissue damage and scar formation. Similar observations have been made in children with acute pyelonephritic episodes, in whom early and aggressive antibiotic treatment prevented subsequent kidney scars, while delayed treatment did not.

Key words

Pyelonephritis Renal scars Renal inflammation Polymorphonuclear leucocytes Urinary tract infections 


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  1. 1.
    Angell ME, Relman AS, Robbins SL (1968) “Active” chronic pyelonephritis without evidence of bacterial infection. N Engl J Med 278:1303–1308PubMedGoogle Scholar
  2. 2.
    Aoki S, Imamura S, Aoki M, McCabe WR (1969) “Abacterial” and bacterial pyelonephritis. Immunofluorescent localization of bacterial antigen. N Engl J Med 281: 1375–1382PubMedGoogle Scholar
  3. 3.
    Kalmanson GM, Sommers SC, Guze LB (1965) Pyelonephritis. VII. Experimental ascending infection with progression of lesions in the absence of bacteria. Arch Pathol 80:509–516PubMedGoogle Scholar
  4. 4.
    Glassock RJ, Kalmanson GM, Guze LB (1974) Pyelonephritis. XVIII. Effect of treatment on the pathology of enterococcal pyelonephritis in the rat. Am J Pathol 76: 49–60PubMedGoogle Scholar
  5. 5.
    Guze LB, Kalmanson GM (1964) Persistence of bacteria in “protoplast” form after apparent cure of pyelonephritis in rats. Science 143:1340–1341Google Scholar
  6. 6.
    Strong DW, Lawson RK, Hodges CV (1974) Experimentally induced pyelonephritis using bacterial antigen and its prevention with immunosuppression. Invest Urol 11: 479–485PubMedGoogle Scholar
  7. 7.
    Miller TE, North D (1971) The cellular kinetics of the immune response in pyelonephritis. J Lab Clin Med 78: 891–904PubMedGoogle Scholar
  8. 8.
    Spencer AG, Fairhead AP (1972) The cellular immune response in experimentalEscherichia coli pyelonephritis in the rat. Nephron 9:325–336PubMedGoogle Scholar
  9. 9.
    Kovats TG (1961) The role of endotoxin in autoimmune processes. Naturwissenschaften 49:572–573Google Scholar
  10. 10.
    Holmgren J, Hanson LA, Holm SE, Kaijser B (1971) An antigenic relationship between kidney and certainEscherichia coli strains. Int Arch Allergy Appl Immunol 41:463–474PubMedGoogle Scholar
  11. 11.
    Kalmanson GM, Guze LB (1963) Pyelonephritis. An attempt to demonstrate anti-kidney antibody in the sera of patients with chronic bacteriuria. Am J Med Sci 246: 532–536PubMedGoogle Scholar
  12. 12.
    Miller TE, Smith JW, Lehmann JW, Sanford JP (1970) Autoimmunity in chronic experimental pyelonephritis. J Infect Dis 122:191–195PubMedGoogle Scholar
  13. 13.
    Coles GA, Chick S, Hopkins M, Ling R, Radford NJ (1974) The role of the T cell in experimental pyelonephritis. Clin Exp Immunol 16:629–636Google Scholar
  14. 14.
    Miller T, Burnham S, Simpson G (1975) Selective deficiency of thymus-derived lymphocytes in experimental pyelonephritis. Kidney Int 8:88–97PubMedGoogle Scholar
  15. 15.
    Glauser MP, Lyons JM, Braude AI (1978) Prevention of chronic experimental pyelonephritis by suppression of acute suppuration. J Clin Invest 61:403–407PubMedGoogle Scholar
  16. 16.
    Cotran RS (1969) Experimental pyelonephritis. In: Rouiller C, Muller AF (eds) The kidney: morphology, biochemistry, physiology, vol II. Academic Press, New York, pp 269–361Google Scholar
  17. 17.
    Mintter PM, Andriole VT (1985) Role of Tamm-Horsfall protein in the pathogenesis of reflux nephropathy and chronic pyelonephritis. Eur J Clin Microbiol 4:540–543PubMedGoogle Scholar
  18. 18.
    Mayrer AR, Miniter P, Andriole VT (1983) Immunopathogenesis of chronic pyelonephritis. Am J Med 74: S59-S70Google Scholar
  19. 19.
    Mayrer AR, Kashgarian M, Ruddle NH, Marier R, Hodson CJ, Richards FF, Andriole VT (1982) Tubulointerstinal nephritis and immunologic responses to Tamm-Horsfall protein in rabbits challenged with homologous urine or Tamm-Horsfall protein. J Immunol 128:2634–2642PubMedGoogle Scholar
  20. 20.
    Brooks SJD, Lyons JM, Braude AI (1974) Immunization against retrograde pyelonephritis. I. Production of an experimental model of severe ascendingEscherichia coli pyelonephritis without bacteremia in rats. Am J Pathol 74: 345–354PubMedGoogle Scholar
  21. 21.
    Brooks SJD, Lyons JM, Braude AI (1977) Immunization against pyelonephritis. III. Protection against chronicEscherichia coli pyelonephritis by vaccination. J Infect Dis 136:633–639PubMedGoogle Scholar
  22. 22.
    Glauser MP, Francioli P, Bille J, Bonard M, Myelan P (1983) Effect of indomethacin on the incidence of experimentalEscherichia coli pyelonephritis. Infect Immun 40: 529–533PubMedGoogle Scholar
  23. 23.
    Glauser MP, Lyons JM, Braude AI (1979) Synergism of ampicillin and gentamicin against obstructive pyelonephritis due toEscherichia coli in rats. J Infect Dis 139: 133–140PubMedGoogle Scholar
  24. 24.
    Miller T, Phillips S (1981) Pyelonephritis: The relationship between infection, renal scarring, and antimicrobial therapy. Kidney Int 19:654–662PubMedGoogle Scholar
  25. 25.
    Slotki IN, Asscher AW (1982) Prevention of scarring in experimental pyelonephritis in the rat by early antibiotic therapy. Nephron 30:262–268PubMedGoogle Scholar
  26. 26.
    Ransley PG, Risdon RA (1981) Reflux nephropathy: effects of antimicrobial therapy on the evolution of the early pyelonephritic scar. Kidney Int 20:733–742PubMedGoogle Scholar
  27. 27.
    Winberg J, Bergström T, Jacobsson B (1975) Morbidity, age and sex distribution, recurrences and renal scarring in symptomatic urinary tract infection in childhood. Kidney Int 8:S101-S106Google Scholar
  28. 28.
    Winter AL, Hardy BE, Alton DJ, Arbus GS, Churchill BM (1983) Acquired renal scars in children. J Urol 129: 1190–1194PubMedGoogle Scholar
  29. 29.
    Westenfelder M, Galanos C (1974) Experimental lipid A-induced nephritis in the dog. A possible role of lipid A in the pathogenesis of abacterial chronic pyelonephritis. Infection 2:174–177PubMedGoogle Scholar
  30. 30.
    Issekutz AC, Bhimji S (1982) Role for endotoxin in the leukocyte infiltration accompanyingEscherichia coli inflammation. Infect Immun 36:558–566PubMedGoogle Scholar
  31. 31.
    Weissmann G, Smolen JE, Korchak HM (1980) Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303:27–34PubMedGoogle Scholar
  32. 32.
    Babior BM (1978) Oxygen-dependent microbial killing by phagocytes. N Engl J Med 298:659–669, 721–725PubMedGoogle Scholar
  33. 33.
    McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312:159–163PubMedGoogle Scholar
  34. 34.
    Bille J, Glauser MP (1982) Protection against chronic pyelonephritis in rats by suppression of acute suppuration: effect of colchicine and neutropenia. J Infect Dis 146: 220–226PubMedGoogle Scholar
  35. 35.
    Miller TE, Burnham S, North JDK (1976) Immunological enhancement in the pathogenesis of pyelonephritis. Clin Exp Immunol 24:336–345PubMedGoogle Scholar
  36. 36.
    Sanford JP, Hunter BW, Donaldson P (1962) Localization and fate ofEscherichia coli in hematogenous pyelonephritis. J Exp Med 116:285–294PubMedGoogle Scholar
  37. 37.
    Cotran RS (1963) Retrograde Proteus pyelonephritis in rats: localization of antigen and antibody in treated sterile pyelonephritic kidneys. J Exp Med 117:813–821PubMedGoogle Scholar
  38. 38.
    Ivanyi B, Ormos J, Lantos J (1983) Tubulointerstitial inflammation, cast formation, and renal parenchymal damage in experimental pyelonephritis. Am J Pathol 113: 300–308PubMedGoogle Scholar
  39. 39.
    Bradley PB, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation. Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209PubMedGoogle Scholar
  40. 40.
    Meylan P, Glauser MP (1984) Relationship between the polymorphonuclear leukocyte infiltration during acute exudative experimental pyelonephritis and the development of chronic pyelonephritis. Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, abstract 696Google Scholar
  41. 41.
    Meylan PR, Bonard M, Glauser MP (1985) Effect of dexamethasone administered during acute exudative pyelonephritis on kidney scars in rats. Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, abstract 329Google Scholar
  42. 42.
    Meylan PR, Glauser MP (1986) Effect of decomplementation and phenylbutazone on polymorphonuclear leukocytes infiltration during acute exudativeE. coli pyelonephritis. Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, abstract 1163Google Scholar
  43. 43.
    Wilson DM, Ormrod DJ, Miller TE (1980) Role of complement in chemotaxis: study of a localized infection. Infect Immun 29:8–12PubMedGoogle Scholar
  44. 44.
    Sullivan MJ, Harvey RA, Shimamura T (1977) The effects of cobra venom factor, an inhibitor of the complement system, on the sequence of morphological events in the rat kidney in experimental pyelonephritis. Yale J Biol Med 50:267–273PubMedGoogle Scholar
  45. 45.
    Roberts JA, Roth JK, Domingue G, Lewis RW, Kaack B, Baskin G (1983) Immunology of pyelonephritis in the primate model. VI. Effect of complement depletion. J Urol 129:193–196PubMedGoogle Scholar
  46. 46.
    Harber MJ, Topley N, Jenner DE, Mackenzie RK, Steadman R, Knowlden JM, Asscher AW (1986) Virulence factors of urinary pathogens in relation to kidney scarring. In: Asscher AW, Brumfitt W (eds) Microbial diseases in nephrology Wiley, New York, pp 69–82Google Scholar
  47. 47.
    Stendahl O, Molin L, Dahlgren C (1978) The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis. J Clin Invest 61:214–220Google Scholar
  48. 48.
    Meylan PR, Bille J, Glauser MP (1984) Protection against chronic pyelonephritis by dapsone administered during acute exudative pyelonephritis. Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, abstract 697Google Scholar

Copyright information

© IPNA 1987

Authors and Affiliations

  • M. P. Glauser
    • 1
  • P. Meylan
    • 1
  • J. Bille
    • 1
  1. 1.Division of Infectious Diseases, Department of Internal MedicineCentre Hospitalier Universitaire VaudoisLausanneSwitzerland

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