Skip to main content
SpringerLink
Log in

Medikamentöse Behandlung der chronisch verlaufenden Glomerulonephritiden: Pro

In favour of drug treatment of chronic glomerulonephritides (GN)

  • Zum Geleit
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

This paper sets out the arguments for drug treatment of chronic glomerulonephritides (GN). Although the pathogenesis and mechanism of progression of chronic GN remained to be clarified, on the basis of controlled studies performed to date, there is a strong case to be made for an aggressive treatment approach to this disease spectrum. For instance, in patients with idiopathicmembranous glomerulonephritis a six months treatment with chlorambucil (0.2 mg/KG/day) or prednisone (0.6 mg/KG/day) each given once a day over a period of three months has recently been shown to improve the outcome of the renal functional parameters after three years follow up. In another controlled trial a daily dose of 225 mg dipyridamole and 975 mg aspirin given over 12 months in patients withmembrano-proliferative GN type I has been reported to normalize the increased platelet consumption rate and to stabilize the glomerular filtration rate. A third trial has demonstrated that the combined use of cyclophosphamide (100 mg/day) and prednisone (30 mg/day) over several months was superior to the use of prednisone alone (40 mg/day) in improving the long-term prognosis ofdiffuse-proliferative lupus nephritis (type IV, WHO).

In some entities, however, as in IgA-nephritis there is still no evidence for a specific treatment improving the course of the chronic glomerular disease. Other therapeutic problems have to be solved: thus, in patients withminimal change nephropathy with a steroid dependent nephrotic syndrome the benefit of cyclophosphamide (given over three months) or of cyclosporin A is still being investigated. Furthermore, there is some evidence that progression of chronic GN, particularly that of glomerular sclerosing, can be prevented by a low protein diet. The role of eicosanoides and their inhibitors in this context has not yet been fully investigated.

The different drug trials and new therapeutic concepts indicate a rapid development of chronic GN treatment. Therefore, a failure to treat actively is difficult to understand.

Zusammenfassung

Pathogenese und Mechanismen der Progression chronischer Glomerulonephritiden (GN) sind bisher nicht geklärt. Dennoch gibt es erfolgversprechende, prospektive, kontrollierte Therapie-Studien sowie neue Therapie-Ansätze. So wurden beispielsweise Patienten mit idiopathischermembranöser GN monatlich mit Chlorambucil (0,2 mg/kg/Tag) oder Prednison (0,6 mg/kg/Tag) im Wechsel über sechs Monate behandelt. Im Vergleich zu den unbehandelten zeigte sich bei den behandelten Patienten innerhalb von drei Jahren ein günstiger Verlauf der Nierenfunktionsparameter. In einer anderen Studie erhielten Patienten mitmembrano-proliferativer GN Typ I über ein Jahr täglich 975 mg Aspirin und 225 mg Dipyridamol. Bei den behandelten trat im Gegensatz zu den nichtbehandelten Patienten eine Stabilisierung der Nierenfunktion und eine Normalisierung der vorher beschleunigten Thrombozyten-Überlebensrate ein. In einer weiteren kontrollierten Therapie-Studie wurde gezeigt, daß die Langzeit-Prognose derdiffus-proliferativen Lupus-Nephritis (Typ IV WHO) besser ist, wenn eine kombinierte Behandlung mit Cyclophosphamid (100 mg/Tag) und Prednison (30 mg/Tag) über mehrere Monate erfolgt als eine alleinige Prednison-Behandlung (40 mg/Tag).

Dagegen gibt es bisher bei einigen Formen der chronischen GN, z.B. derIgA-Nephritis, noch keine Evidenz für eine Therapie, die den Verlauf der Nephritis entscheidend beeinflussen kann. Neuere Therapie-Ansätze, wie die Gabe von Cyclophosphamid (über drei Monate) oder von Cyclosporin A beiglomerulärer Minimal-Läsion mit steroid-abhängigem nephrotischen Syndrom, werden in Therapie-Studien überprüft. Einige kontrolliert durchgeführte Untersuchungen weisen darauf hin, daß die Progression der chronischen GN durch eine Diät mit geringem Proteingehalt günstig beeinflußt werden kann. Der Einfluß von Eicosanoiden und deren Inhibitoren auf den Verlauf chronischer GN, speziell der glomerulären Sklerosierung, ist bisher noch nicht ausreichend untersucht worden.

Insgesamt ist eine Entwicklung zu einer zunehmend differenzierten medikamentösen Behandlung der chronischen GN festzustellen, die generell durch die Bereitschaft zu einem aktiven therapeutischen Vorgehen unterstützt werden sollte.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  1. Andrassy K, Waldherr R, Ritz E (1985) Medikamentöse Behandlung der chronisch verlaufenden Glomerulonephritiden: Contra. Klin Wochenschr 63:978–987

    Google Scholar 

  2. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1981) Alternate-day prednisone is more effective than intermittent prednisone in frequently relapsing nephrotic syndrome. Eur J Pediatr 135:229–237

    Google Scholar 

  3. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454

    Google Scholar 

  4. Barnett HL (1976) The natural and treatment history of glomerular diseases in children. Proc 6th Int Congress of Nephrol, Karger, Basel, pp 470–485

    Google Scholar 

  5. Barton CH, Vaziri ND, Spear GS (1980) Nephrotic syndrome associated with adeno-carcinoma of the breast. Am J Med 68:308–312

    Google Scholar 

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

    Google Scholar 

  7. Brenner BM, Meyer TW, Hostetter TH (1982) Dietary protein intake and the progressive nature of kidney disease. N Engl J Med 307:652–659

    Google Scholar 

  8. Brenner BM, Meyer TW (1984) Mechanisms of progression of renal disease. Proc 9th Int Congress of Nephrol, Springer, New York Heidelberg, Vol II, pp 1233–1246

    Google Scholar 

  9. Brodehl J, Hoyer PF (1985) Cyclosporin A treatment of idiopathic nephrotic syndrome in children (minimal disease and focal segmental glomerulosclerosis). Int Workshop on cyclosporin in auto-immune diseases, Basel, 1985 (im Druck)

  10. Cameron JS (1984) Treatment of glomerular diseases. Treatment of glomerulonephritis based on knowledge of its pathogenesis. Proc 9th Int Congress of Nephrol, Springer, New York Heidelberg, Vol II, pp 1445–1463

    Google Scholar 

  11. Cannon PJ (1984) Eicosanoids and the blood vessel wall. Circulation 70:523–528

    Google Scholar 

  12. Carette S, Klippel JH, Decker JL, Austin HA, Plotz PH, Steinberg AD, Balow JE (1983) Controlled studies of oral immunosuppressive drugs in lupus nephritis. A long-term follow up. Ann Intern Med 99:1–8

    Google Scholar 

  13. Cats S, Terasaki PI, Perdue S, Mickey MR (1985) Preferential effectiveness of cyclosporin in patients receiving kidney transplants after glomerulonephritis. Lancet I:490–491

    Google Scholar 

  14. Cattran D, Cardella C, Charron J, Roscoe E, Bear R, Corey P (1984) Results of a controlled trial of alternate day prednisone in idiopathic membranous glomerulopathy. 9th Int Congress of Nephrology, 74A (Abstract)

  15. Cattran D, Cardella C, Roscoe E, Charron J, Rance PC, Ritchie SM, Corey P (1985) Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int 27:436–441

    Google Scholar 

  16. Ciabattoni G, Cinotti G, Pierucci A, Simonetti B, Manzi M, Pugliese F, Barsotti P, Pecci G, Taggi F, Patrono C (1984) Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. N Engl J Med 310:279–283

    Google Scholar 

  17. Clarkson AR, Woodroffe AJ (1984) Therapeutic perspectives in mesangial IgA-nephropathy. Contr Nephrol 40:187–194

    Google Scholar 

  18. Coggins CH (1981) Minimal change nephrosis in adults. Proc 8th Int Congress of Nephrol, Basel, Karger, pp 336–344

    Google Scholar 

  19. Coggins C, Churg I, Spargo B, Cotran R, Burkholder P, Rosen S, Pinn V, Glassock RJ (1981) US Cooperative Study of Adult Nephrotic Syndrome. Unpublished observations. In: Primary glomerular disease (chapter 26). In: Brenner BM, Rector FC (eds) The Kidney, WB Saunders, Philadelphia London Toronto, p 1436

    Google Scholar 

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

    Google Scholar 

  21. Couser WG, Wagonfeld JB, Spargo BH, Lewis EJ (1974) Glomerular deposition of tumor antigen in membranous nephropathy associated with colonic carcinoma. Am J Med 57:962–970

    Google Scholar 

  22. Donadio JV (1982) Primary glomerular disease: To treat or not to treat? Contr Nephrol 33:86–103

    Google Scholar 

  23. Donadio JV, Anderson CF, Mitchell JC, Holley KE, Ilstrup DM, Fuster V, Chesebro JH (1984) Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. N Engl J Med 310:1421–1426

    Google Scholar 

  24. Donadio JV, Holley KE, Anderson CF, Taylor WF (1974) Controlled trial of cyclophosphamide in idiopathic membranous nephropathy. Kidney Int 6:431–439

    Google Scholar 

  25. Donadio JV, Holley KE, Ferguson RH, Ilstrup DM (1978) Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide. N Engl J Med 299:1151–1155

    Google Scholar 

  26. Donker AJ, Rosman JB, Piers-Becht TP, Sluiter WJ (1985) Effect of protein restriction in chronic renal insufficiency: A prospective randomized trial. Kidney Int 27:137 (Abstract)

    Google Scholar 

  27. Frölich IC, Fejes-Toth G (1982) Renal prostaglandins. Klin Wochenschr 60:1155–1164

    Google Scholar 

  28. Futrakul P, Poshyachinda M, Mitrakul C (1978) Focal sclerosing glomerulonephritis: A kinetic evaluation of hemostasis and the effect of anticoagulant therapy: A controlled study. Clin Nephrol 10:180–186

    Google Scholar 

  29. Geary DF, Farine M, Thorner P, Baumal R (1984) Response to cyclophosphamide in steroid-resistant focal segmental glomerulosclerosis: A reappraisal. Clin Nephrol 22:109–113

    Google Scholar 

  30. German Glomerulonephritis Research Group (1976) A controlled multicenter trial of cyclophosphamide and indomethacin in chronic glomerulonephritis. In: Kluthe R, Vogt A, Batsford SR (eds) Glomerulonephritis. Georg Thieme, Stuttgart, pp 196–201

    Google Scholar 

  31. Glassock RJ, Goldstein DA, Finander P, Koss M, Kitridou R, Border W (1981) Glomerulonephritis in systemic lupus erythematosus. Am J Nephrol 1:53–67

    Google Scholar 

  32. Habib R, Churg J, Bernstein J, Cameron JS, Cohen AH, Gagnadoux MF, Lewis EJ (1984) Minimal change disease, mesangioproliferative glomerulonephritis and focal sclerosis: Individual entities or a spectrum of disease? Proc 9th Int Congress of Nephrol, Springer, New York Heidelberg, Vol I, pp 634–644

    Google Scholar 

  33. Hamazaki T, Tateno S, Shishido H (1984) Eicosapentaenoic acid and IgA-nephropathy. Lancet I:1017–1018

    Google Scholar 

  34. Hutchison FN, Gambertoglio J, Jiminez I, Jones H (1985) Effect of reduced dietary protein intake on albumin homeostasis and albuminuria in man. Kidney Int. 27:141 (Abstract)

    Google Scholar 

  35. Ito H, Hattoni S, Matusda I, Amamiga S, Hajikano H, Yoshizawa H, Migakawa Y, Mayumi M (1981) Hepatitis B e antigen-mediated membranous glomerulonephritis. Correlation of ultrastructural changes with HBeAg in the serum and glomeruli. Lab Invest 44:214–220

    Google Scholar 

  36. Kincaid-Smith P (1985) Mesangial IgA-nephropathy. Brit Med J 290:96–97

    Google Scholar 

  37. Kluthe R, Oechslin D, Quirin H, Jesdinsky HJ (1971) Six years experience with a special low protein diet. In: Kluthe R, Berlyne G, Burton B (eds) Uraemia: Pathogenesis, Diagnosis and Treatment. Thieme, Stuttgart, pp 250–257

    Google Scholar 

  38. Kühn K, Menninger H (1984) Is renal biopsy overused in patients with systemic lupus erythematosus? Contr Nephrol 43:45–50

    Google Scholar 

  39. Levy M, Kleinknecht C (1980) Membranous glomerulonephritis and hepatitis B infection. Nephron 26:259–265

    Google Scholar 

  40. Lewis EJ, Coggins CH, West CD, Spitzer A, Zimmermann SW, Lachin J, Winslade W, Cattran DC (1984) Are randomized trials in kidney disease worthwhile? Proc 9th Int Congress of Nephrol, Springer, New York Heidelberg, Vol II, pp 1437–1444

    Google Scholar 

  41. Llach F, Koffler A, Massry SG (1975) On the incidence of renal vein thrombosis and nephrotic syndrome. Ann Intern Med 83:8–17

    Google Scholar 

  42. McEnery PT, McAdams AJ, West CD (1980) Membranoproliferative glomerulonephritis: improved survival with alternate-day prednisone therapy. Clin Nephrol 13:117–124

    Google Scholar 

  43. Michielsen P, Vanrenterghem Y, Roels L (1976) Treatment of chronic glomerulonephritis with indomethacin. In: Kluthe R, Vogt A, Batsford SR (eds) Glomerulonephritis. Georg Thieme Publishers, Stuttgart, pp 149–153

    Google Scholar 

  44. Naray-Fejes-Toth A, Fejes-Toth G, Fischer C, Frölich JC (1984) Effect of dexamethasone on in vivo prostanoid production in the rabbit. J Clin Invest 74:120–123

    Google Scholar 

  45. Niwa T, Maeda K, Naotsuka Y, Asada H, Kobayashi S, Yokoyama M, Kawaguchi S, Shibata M (1982) Improvement of renal function with prostaglandin E1 infusion in patients with chronic renal disease. Lancet I:687

    Google Scholar 

  46. Noel LH, Zanetti M, Droz D, Barbanel C (1979) Long-term prognosis of idiopathic membranous glomerulonephritis: study of 116 untreated patients. Am J Med 66:82–90

    Google Scholar 

  47. Oldrizzi L, Rugiu C, Valvo E, Lupo A, Loschiavo C, Lammaro L, Tessitore N, Fabris A, Panzetta G, Maschio G (1985) Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet. Kidney Int 27:553–557

    Google Scholar 

  48. Ponticelli C, Zucchelli P, Banfi G, Cagnoli L, Scalia P, Pasquali S, Imbasciati E (1982) Treatment of diffuse proliferative lupus nephritis by intravenous high-dose methyl-prednisolone. Q J Med 201:16–24

    Google Scholar 

  49. Ponticelli C, Zucchelli P, Imbasciati E, Cagnoli L, Pozzi C, Grassi C, Limido D, Pasquali S, Passerini P, Volpini T, Locatelli F (1982) Controlled trial of monthly alternated courses of steroid and chlorambucil for idiopathic membranous nephropathy. Proc EDTA 19:717–723

    Google Scholar 

  50. Pricket JD, Robinson DR, Steinberg AD (1981) Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB × NZW F1 mice. J Clin Invest 68:556–559

    Google Scholar 

  51. Rees AJ, Lockwood CM (1982) Immunosuppressive drugs in clinical practice. In: Lachmann TJ, Peters DK (eds) Clinical aspects of immunology. Blackwell, Oxford, pp 507–564

    Google Scholar 

  52. Report of the International Study of Kidney Disease in Children (1974) Prospective, controlled trial of cyclophosphamid therapy in children with the nephrotic syndrome. Lancet II:423–427

    Google Scholar 

  53. Report of the International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564

    Google Scholar 

  54. Report of the International Study of Kidney Disease in Children (1981) Alternate-day steroid therapy in membrano-proliferative glomerulonephritis: a randomized controlled clinical trial. 14th Ann Meet of Am Soc Nephrol 23A (Abstract)

  55. Rose G (1976) Medical Research Concil Trials. In: Kluthe R, Vogt A, Batsford SR (eds) Glomerulonephritis. Georg Thieme Publishers, Stuttgart, pp 174–182

    Google Scholar 

  56. Saito H, Ideura T, Takeuchi J (1984) Effects of a selective thromboxane A2 synthetase inhibitor on immune complex glomerulonephritis. Nephron 36:38–45

    Google Scholar 

  57. Sobel AT, Heslan JT, Branellec A, Lagrue G (1984) Vascular permeability factor and other lymphokines in nephrotic syndrome. Proc 6th Int Symp of Pediatic Nephrol, Springer, Berlin New York, pp 264–267

    Google Scholar 

  58. Strom TB (1984) Immunsuppressive agents in renal transplantation. Kidney Int 26:353–365

    Google Scholar 

  59. Tiller DJ, Clarkson AR, Mathew T, Thompson N, Row G, Lauer C, Hobbs J, Semour A (1981) A prospective randomized trial in the use of cyclophosphamide, dipyridamole, and warfarin in membranous and mesangio-capillary glomerulonephritis. Proc 8th Int Congress of Nephrol, Karger, Basel, pp 345–351

    Google Scholar 

  60. Trompeter RS: Unpublished observations

  61. Trompeter RS, Evans PR, Barratt TM (1981) Gonadal function in boys with steroid-responsive nephrotic syndrome treated with cyclophosphamide for short periods. Lancet I:1177–1179

    Google Scholar 

  62. Vanrenterghem Y, Roels L, van Damme B, Michielsen P (1979) Influence of indomethacin treatment on the spontaneous glomerulosclerosis of the rat. Kidney Int 16:659 (Abstract)

    Google Scholar 

  63. Waldherr R (1984) Predictive value of renal biopsy in lupus nephritis. Contr Nephrol 43:36–44

    Google Scholar 

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

    Google Scholar 

  65. Zucchelli P, Zuccala A, Santoro A, Esposti ED, Sturani A, Chiarini C (1984) Characteristics of hypertension in primary IgA-glomerulonephritis. Contr Nephrol 40:174–181

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zentrum Innere Medizin und Dermatologie der Medizinischen Hochschule Hannover, Germany

    K. Kühn & K. M. Koch

  2. Kinderklinik der Medizinischen Hochschule Hannover, Germany

    J. Brodehl

  3. Pathologisches Institut der Universität Göttingen, Germany

    U. Helmchen

Authors
  1. K. Kühn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Brodehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. M. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U. Helmchen
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Prof. Dr. med. Fritz Hartmann zum 65. Geburtstag gewidmet

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kühn, K., Brodehl, J., Koch, K.M. et al. Medikamentöse Behandlung der chronisch verlaufenden Glomerulonephritiden: Pro. Klin Wochenschr 63, 967–977 (1985). https://doi.org/10.1007/BF01738152

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01738152

Key words

Schlüsselwörter

Search

Navigation