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Medikamentöse Behandlung der chronisch verlaufenden Glomerulonephritiden: Contra

Drug treatment of chronic glomerulonephritides: Contra

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Summary

It is controversial whether the pathomechanisms involved in chronic idiopathic glomerulonephritis are susceptible to therapeutic intervention. Etiological therapy, i.e. elimintion of the responsible antigen, is possible only in exceptional cases, e.g. tropical diseases, infected ventriculoatrial shunt etc. Antiinflammatory therapy directed against pathomechanisms initiating or maintaining glomerular inflammation has an uncertain theoretical foundation because of lack of knowledge relating to the exact steps mediating tissue injury. Recent studies suggest keyroles for terminal components of complement system, products of lipoxygenase pathway of arachidonic acid and oxygen radicals — all of which are not readily influenced by available therapeutic modulaties. Finally, progression of glomerular inflammation to renal failure is usually not the cause of cumulative acute inflammatory glomerular lesions but rather the consequence of progressive sclerosis of glomeruli, arterioles and interstitium. As examples of controlled intervention trials, studies on extramembranous and membranoproliferative glomerulonephritis are discussed. The studies show limited and not always statistically significant influence on renal function, however, at the expense of considerable side effects. It is concluded that it is highly questionable whether inflammatory pathomechanisms are influenced by currently available drugs. However, therapeutic nihilism is not appropriate given modalities to influence mechanisms of nonspecific damage, e.g. by antihypertensive medication or dietary intervention.

Zusammenfassung

Das Thema der therapeutischen Beeinflussung der entzündlichen Pathomechanismen bei chronisch-idiopathischer Glomerulonephritis bedarf einiger kritischer Anmerkungen. Eine ätiologische Behandlung ist nur in Ausnahmefällen möglich (infektiöse Tropenkrankheiten, infizierter ventrikuloatrialer Shunt etc.). Einer erfolgreichen Beeinflussung der Pathomechanismen, welche die glomeruläre Entzündung auslösen und unterhalten, steht unsere Unkenntnis über die im einzelnen verantwortlichen Schritte entgegen. Neuere Untersuchungen legen Schlüsselrollen für die terminale Komponente des Komplementsystems, Produkte des Lipoxygenaseabbauweges der Arachidonsäure sowie Sauerstoffradikale nahe, welche therapeutisch nicht oder nur beschränkt beeinflußbar sind. Ferner beruht die Progredienz glomerulärer Entzündungen in die Niereninsuffizienz in der Regel auf fortschreitender Sklerosierung von Glomerulus, Gefäßen und Interstitium und nicht auf zunehmenden aktiv entzündlichen glomerulären Läsionen. Beispielhaft wurden bei der Sichtung der veröffentlichten kontrollierten Therapiestudien die Untersuchungen bei extramembranöser und membranoproliferativer Glomerulonephritis herausgegriffen. Hierbei wurde eine im Ausmaß nur beschränkte, und nicht in allen Studien gesicherte, Beeinflussung der Nierenfunktion gefunden, der andererseits erhebliche Nebenwirkungen gegenüberstehen. Eine abschließende Wertung kommt zu dem Urteil, daß eine medikamentöse Beeinflussung der entzündlichen Pathomechanismen fragwürdig ist, daß jedoch ein therapeutischer Nihilismus nicht angezeigt ist angesichts der Beeinflußbarkeit unspezifischer Schädigungsmechanismen (antihypertensive Behandlung, diätetische Intervention).

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References

  1. 1.

    Frerichs T (1851) Die Bright'sche Nierenerkrankung und deren Behandlung. Vieweg Verlag Braunschweig

  2. 2.

    Cameron J (1984) Treatment of glomerulonephritis based on knowledge of its pathogenesis. In: Robinson R (ed) Nephrology, Vol II. Springer-Verlag, Heidelberg, pp 1445–1463

  3. 3.

    Cameron J (1982) Glomerulonephritis: current problems and understanding. J Lab Clin Med 99:755–787

  4. 4.

    Adler S, Baker P, Pritzl P, Couser P (1984) Detection of terminal complement components in experimental immune glomerular injury. Kidney Int 26:830–837

  5. 5.

    Rehan A, Johnson K, Kunkel R, Wiggins R (1985) Role of oxygen radicals in phorbol myristate acetate-induced glomerular injury. Kidney Int 27:503–511

  6. 6.

    Dunn M, Lianos E, Stork J (1984) Glomerular arachidonic acid metabolism in nephrotoxic serum nephritis. In: Robinson R (ed) Nephrology, Vol I. Springer, Heidelberg, pp 601–608

  7. 7.

    Luetscher J, Deming A, Harvey G, Lew W, Pool L (1950) Treatment of nephrosis with cortisone. J Clin Invest 29:1576–1587

  8. 8.

    Addis T, Marmorston J, Goodman H, Sellers A, Smith M (1950) Effect of adrenalectomy on spontaneous and induced proteinuria in the rat. Proc Soc Exp Biol Med 74:43–46

  9. 9.

    Rambausek M, Seelig H, Andrassy K, Waldherr R, Kejry I, Lenhard V, Ritz E (1983) Mesangiale IgA-Glomerulonephritis. Neue Aspekte zur Diagnose, Klinik und Prognose. Dtsch Med Wochenschr 108:125–130

  10. 10.

    Rambausek M, Waldherr R, Andrassy K, Ritz E (1984) Hypertension in mesangial IgA glomerulonephritis. Proc EDTA 21:693–696

  11. 11.

    Gallo G, Feiner A, Steele M, Schacht R, Gluck M, Baldwin D (1978) Role of intrarenal vascular sclerosis in progression of poststreptococcal glomerulonephritis. Clin Nephrol 13:49–57

  12. 12.

    Bohle A, Gärtner HV, Haberke HG, Krück F (1984) Die Niere. Schattauer, Stuttgart

  13. 13.

    Ritz E, Mauerhoff T, Andrassy K, Kreusser W (1983) Lupus Nephritis. Wann, wie und womit soll behandelt werden? Dtsch Med Wochenschr 108:591–594

  14. 14.

    Austin H, Muenz L, Joyce K, Antonovych T, Balow J (1984) Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Intern 25:689–695

  15. 15.

    Decker J, Steinberg A, Reinertson J, Plotz P, Balow J, Klippel J (1979) Systemic lupus erythematosus: evolving concepts. Ann Int Med 91:587–604

  16. 16.

    Collaborative study of the adult idiopathic nephrotic syndrome. A controlled study of short-term prednisone treatment in adults with membranous nephropathy (1979) New Engl J Med 301:1301–1306

  17. 17.

    Noel L, Zanetti M, Droz D, Barbanel C (1979) Long-term prognosis of idiopathic membranous glomerulonephritis. Am J Med 66:82–90

  18. 18.

    Donadio J (1982) Primary glomerular disease: to treat or not to treat. Contr Nephrol 33:86–103, Karger, Basel

  19. 19.

    Sarre H (1963) Kortikosteroidtherapie beim nephrotischen Syndrom. Med Klin 58:672–676

  20. 20.

    Black D, Rose G, Brewer D (1970) Controlled trial of prednisone in adult patients with the nephrotic syndrome. Brit Med J 3:421–426

  21. 21.

    Medical Research Council (1971) Controlled trial of azathioprine and prednosone in chronic renal disease. Report of a Medical Research Council Working Party. Brit Med J 2:239–247

  22. 22.

    Donadio J, Holley K, Anderson C, Taylor W (1974) Controlled trial of cyclophosphamide in idiopathic membranous nephropathy. Kidney Int 6:431–439

  23. 23.

    Lagrue G, Bernard D, Bariety J, Druet P, Guenel J (1975) Controlled trial of chlorambucil and azathioprine in idiopathic chronic glomerulonephritis (Abstract), Kidney Int 8:274

  24. 24.

    Tiller D, Clarkson A, Mathew T, Thompson N, Row G, Lauer C, Hobbs J, Seymour A (1981) A prospektive randomized trial in the use of cyclophosphamide, dipyridamole and warfarin in membranous and mesangiocapillary glomerulonephritis. Proc 8th Int Congr Nephrol Athens, 345–351

  25. 25.

    Ponticelli C, Zucchelli P, Imbasciati E, Cagnoli L et al. (1984) Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. New Engl J Med 310:946–950

  26. 26.

    Vogt A, Batsford S (1982) Eine neue Vorstellung zur Pathogenese der Immunkomlexnephritis. Klin Wochenschr 60:1095–1101

  27. 27.

    Andrassy K, Ritz E, Mauerhoff T, Bommer J (1982) What is the evidence for activated coagulation in glomerulonephritis? Am J Nephrol 2:293–300

  28. 28.

    Kincaid-Smith P, Lacer M, Fairley K, Mathews D (1970) Dipyridamole and anticoagulants in renal disease due to glomerular and vascular lesions. Med J Austral 1:145–151

  29. 29.

    Donadio J, Anderson C, Mitchell J, Holley K, Ilstrup D, Fuster V, Chesebro J (1984) Membranoproliferative Glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. New Engl J Med 310:1421–1426

  30. 30.

    Zimmermann S, Moorthy A, Dreher W, Friedman A, Varanasi A (1983) Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis. Am J Med 75:920–927

  31. 31.

    Cattran D, Cardella C, Roscoe J, Charron R, Rance P, Ritchie S, Vorey P (1985) Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int 27:436–441

  32. 32.

    Andrassy K, Ritz E, Bommer J (1980) Hypercoagulability in the nephrotic syndrome. Klin Wochenschr 58:1029–1036

  33. 33.

    Volhard F (1923) Der arterielle Hochdruck. Verh Dtsch Ges Inn Med 134–175

  34. 34.

    Hostetter Th, Olson J, Rennke H, Venkatachalam M, Brenner B (1981) Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 241:F85-F93

  35. 35.

    Neugarten J, Feiner H, Schacht M, Gallo G, Baldwin D (1982) Aggravation of experimental glomerulonephritis by superimposed clip hypertension. Kidney Int 22:257–263

  36. 36.

    Mogensen C (1982) Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Brit Med J 285:685–688

  37. 37.

    Hasslacher C, Rambausek M, Ritz E (1983) Genesis and management of hypertension in diabetic nephropathy. In: Keen H, Legrain M (eds) Prevention and Treatment of Diabetic Nephropathy. MTP Press, Boston, pp 177–189

  38. 38.

    Brenner B, Meyer T, Hostetter T (1982) Dietary protein intake and the progressive nature of kidney disease. New Engl J Med 307:652–659

  39. 39.

    Rosman J, ter Wee P, Piers-Becht G, Sluiter W, van der Woude F, Meijer S, Donker A (1984) Early protein restriction in chronic renal failure. Proc EDTA 21:567–572

  40. 40.

    Rosman J, ter Wee P, Meijer S, Piers-Brecht T, Sluiter W, Donker A (1984) Prospective randomised trial of erarly dietary protein restriction in chronic renal failure. Lancet II:1291–1295

  41. 41.

    Oldrizzi L, Rugiu C., Vlavo E, Lupo A et al. (1985) Progression of renal failure in patients with renal disease of diverse etiology on protein restricted diet. Kidney Int 27:553–557

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Andrassy, K., Waldherr, R. & Ritz, E. Medikamentöse Behandlung der chronisch verlaufenden Glomerulonephritiden: Contra. Klin Wochenschr 63, 978–987 (1985). https://doi.org/10.1007/BF01738153

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Key words

  • Glomerulonephritis
  • Extramembraneous glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Lupus erythematosus
  • Steroids
  • Antiplatelet agents

Schlüsselwörter

  • Glomerulonephritis
  • Extramembranöse Glomerulonephritis
  • Membranoproliferative Glomerulonephritis
  • Lupus erythematodes
  • Steroide
  • Plättchenhemmer