Glomerulonephritis — 1974

  • J. S. Cameron


  1. 1.

    Glomerulonephritis presents clinically in only a few ways, and similar patients have differing underlying pathogenesis and renal histology. Renal biopsy therefore plays an important part in diagnosis.

  2. 2.

    Patients with a nephrotic syndrome and normal glomeruli (“minimal change” lesion) respond reliably to short (six week) courses of corticosteroids; prolonged treatment is unnecessary and may be dangerous.

  3. 3.

    Half such patients will have only one nephrotic episode, but the remainder relapse at least once, and usually repeatedly. If these relapsing patients cannot be controlled by corticosteroids without unacceptable toxicity, then treatment with a short eight week course of cyclosphamide is justified. This will induce remission lasting an average of three years in both adults and children.

  4. 4.

    Patients with other forms of primary glomerulonephritis associated with glomerular scarring, chronic proteinuria and sometimes declining renal function, can only be harmed by corticosteroids or cytotoxic agents alone or in combination. Although complicated regimes involving the use of anticoagulant and antiplatelet drugs are under trial at the moment, the most important aspect of management is the early detection and effective treatment of their associated hypertension.

  5. 5.

    We now know that patients with chronic glomerulonephritis probably suffer from an inability to clear antigens effectively and hence form small, circulating antigen-antibody complexes which localise in the kidney because of its high bloodflow and high capillary permeability. This inefficiency in clearing antigen represents a relative immunodeficiency. It may be inherited, acquired by circumstances such a protein-energy malnutrition, or perhaps by acquisition of partial tolerance to an antigen with time. Immunosuppression could at least theoretically make this situation worse.

  6. 6.

    The only group of patient in whom immunosuppression for long periods seems to have a place at the moment, is the treatment of nephritis in systemic lupus erythematosus and polyarteritis nodosa. Even here, long term benefit is not yet proven and the régimes produces obvious morbidity and mortality.


The clinical importance of glomerulonephritis has been increased now that terminal renal failure can be treated by either regular dialysis or by transplantation. About two thirds or even three quarters of patients submitted to these procedures have as their primary disease one form of glomerulonephritis or another (Gurlandet al., 1973). Despite the considerable success in treating a previously fatal condition, misery and death still afflict a proportion of patients: the chronic stress of home dialysis is such that not all patients can cope, and one quarter of patients and one half of grafts are dead within two to three years following cadaver transplantation (Tenth report of the International Transplant Registry, 1972). Apart from this human aspect, the cost of these procedures in skilled personnel, time and hard cash is such that we must consider prevention or palliation of glomerular and other chronic renal diseases our goal, and regardall dialysis and transplantation as failures of preventitive medicine, rather than advances in medical technology.


Systemic Lupus Erythematosus Nephritis Glomerulonephritis Lupus Nephritis IRISH Journal 


  1. Amor, B., Kahan, A., Pompidou, A., Delbarre, F. (1972) Efficacité des immunodepresseurs dans la maladie lupique; comparaison d’une série de 13 cas et d’une série temoin de 12 cas. Nouv. Presse Med. 1, 1699.PubMedGoogle Scholar
  2. Arneil, G. C. 1961. 164 children with nephrosis. Lancet ii, 1103.CrossRefGoogle Scholar
  3. Barratt, T. M., Soothill, J. F. 1970. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet ii, 479.CrossRefGoogle Scholar
  4. Barratt, T. M., Cameron, J. S., Chantler, C. S., Soothill, J. F. 1973. Comparative trial of 2 weeks and 8 weeks cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Arch. Dis. Childh., 48, 286.PubMedGoogle Scholar
  5. Becker, E. L. (Editor). 1968. The structural basis of Renal Disease. New York, Hoeber.Google Scholar
  6. Black, D. A. K., Rose, G. A., Brewer, D. B. 1970. Controlled trial of prednisolone in adult patients with the nephrotic syndrome. Brit. Med. J., iii, 421.Google Scholar
  7. Black, D. A. K. (Editor). 1973. Renal Disease. Blackwell; Oxford and London. 3rd Edition.Google Scholar
  8. Brown, C. B., Wilson, D., Turner, D. R., Cameron, J. S., Ogg, C. S., Chantler, C., Gill, D. 1974. Combined immunosuppression and anticoagulants in rapidly progressive glomerulonephritis. Lancet (in press).Google Scholar
  9. Cameron, J. S., Boulton-Jones, M., Robinson, R., Ogg, C. S. 1970. Treatment of lupus nephritis with cyclophosphamide. Lancet ii, 846.Google Scholar
  10. Cameron, J. S. 1971a. The use of immunosuppressant agents in the treatment of glomerulonephritis I: Corticosteroids, II: Immunosuppressant drugs. Proc. Roy. Coll. Phys. (London), 6, 282 and 301.Google Scholar
  11. Cameron, J. S. 1972. Bright’s disease today. Brit. Med. J., iv, 87, 160, 217.Google Scholar
  12. Cameron, J. S. 1973. The natural history of glomerulonephritis. In Renal Disease. Ed. Black, D. A. K. Blackwell, Oxford and London. p. 295.Google Scholar
  13. Cameron, J. S., Turner, D. R., Ogg, C. S., Sharpstone, P., Brown, C. B. 1974a. The nephrotic syndrome with minimal change glomerular lesions. Quart. J. Med. 53, 461.Google Scholar
  14. Cameron, J. S., Chantler, C. S., Ogg, C. S., White, R. H. R. 1974b. Long term stability of remission in nephrotic syndrome after treatment with cyclophosphamide. Brit. Med. J., iv, 7.Google Scholar
  15. Chandra, R. K. 1972. Immuno-incompetence in undernutrition. J. Pediat., 181, 1194.Google Scholar
  16. Churg, J., Habib, R., White, R. H. R. 1970. Pathology of the nephrotic syndrome in children. Lancet i, 1299.CrossRefGoogle Scholar
  17. Cochrane, C. G., Koffler, D. 1973. Immune complex disease in experimental animal and man. Adv. Immunol. 17, 185.CrossRefGoogle Scholar
  18. Donadio, J. V., Holley, K. E., Wagoner, R. D., Ferguson, R. H., McDuffie, F. C. 1972. Treatment of lupus nephritis with predisone and combined predisone and azathioprine. Ann. Int. Med., 77, 829.PubMedGoogle Scholar
  19. Drinkard, J. P., Stanley, T. M., Dornfield, L., Austin, R. C., Barnett, E. C., Pearson, C. M., Vernier, R. L., Adams, D. A., Latta, H., Gonick, H. C. 1970. Azathioprine and prednisone in the treatment of adults with lupus nephritis. Medicine (Baltimore), 49, 411.CrossRefGoogle Scholar
  20. Ellis, A. 1942. Natural history of Bright’s disease: clinical, histological and experimental observations. Lancet i, 34, 72.CrossRefGoogle Scholar
  21. Epstein, W. V., Grausz, H. 1974. Favourable outcome in diffuse proliferative glomerulonephritis of systemic lupus erythematosus. Arthr. Rheum., 17, 129.CrossRefGoogle Scholar
  22. Fairley, K. F., Barrie, J. U., Johnson, W. 1972. Sterility and testicular atrophy related to cyclophosphamide therapy. Lancet, i, 568.CrossRefGoogle Scholar
  23. Feng, P. H., Seah, P. S., Lee, Y. H. 1973. Mortality in systemic lupus erythematosus: a ten year review. Brit. Med. J., iv, 772.Google Scholar
  24. Fudenberg, H. H. 1971. Genetically determined immune deficiency as the predisposing cause of “autoimmunity” and lymphoid neoplasia. Amer. J. Med., 51, 295.PubMedCrossRefGoogle Scholar
  25. Gurland, H. J., Brunner, F. P., Dehn, H. V., Härleh, M., Parsons, F. M., Schärer, K. 1973. Proceedings of the European Dialysis and Transplant Association. Volume X. Edited by Moorehead, J. F., Baillod, R. M. and Mion, C. G. Pitman Medical, London, p. xvii.Google Scholar
  26. George, C. R. P., Clark, W. F., Cameron, J. S. 1975. The platelet and glomerulonephritis. Advances in Nephrology, 5 (in press).Google Scholar
  27. Germuth, F., Rodruigez, L. 1973. The Immunopathology of the human glomerulus. Little Brown, Boston.Google Scholar
  28. Haakenstad, A. O., Mannik, M. 1974. Saturation of the reticuloendothelial system with soluble immune complexes. J. Immunol., 112, 1939.PubMedGoogle Scholar
  29. Hayslett, J. P., Kashgarian, M., Cook, C. D., Spargo, B. H. 1972. The effect of azathioprine on lupus glomerulonephritis. Medicine (Baltimore), 51, 393.CrossRefGoogle Scholar
  30. Josso, F., Cosson, A., Girot, R., Gazengel, C. 1973. Intravascular coagulation and nephropathies. Advances in Nephrology, 3, 175.Google Scholar
  31. Kibukamusoke, J. W. 1973. Nephrotic syndrome of Quartan malaria. Edward Arnold, Bristol.Google Scholar
  32. Kincaid-Smith, P., Mathew, T., Becker, E. L. (Editors). 1973. Glomerulonephritis. 2 vols. John Wiley, New York.Google Scholar
  33. Lipsmeyer, E. A. 1972. Development of malignant cerebral lymphoma in a patient with systemic lupus erythematosus treated with immunosuppression. Arthr. Rheum., 15, 183.CrossRefGoogle Scholar
  34. Merrill, J. 1974. Glomerulonephritis. New Eng., J. Med., 290, 257, 313, 374.Google Scholar
  35. M.R.C. Working Party. Controlled trial of azathioprine and prednisone in chronic renal disease — report of a medical research council working party Brit. Med. J., ii, 239.Google Scholar
  36. Ogg, C. S., Cameron, J. S. 1973. Cyclophosphamide and the treatment of the nephrotic syndrme in adults. Amer. Heart J., 86, 577.CrossRefGoogle Scholar
  37. Passwell, J. H., Steward, M. W., Soothill, J. F. 1974. The effects of protein malnutrition on macrophage function and the amount and affinity of antibody response. Clin. Exp. Immunol., 17, 491.PubMedGoogle Scholar
  38. Penso, J., Lippe, B., Ehrlich, R., Smith, F. G. 1974. Testicular function in prepubertal and pubertal male patients treated with cyclophosphamide for nephrotic syndrome. J. Pediat., 84, 831.PubMedCrossRefGoogle Scholar
  39. Peters, D. K. 1974. The immunological basis of glomerulonephritis. Proc. Roy. Soc. Med., 67, 557.PubMedGoogle Scholar
  40. Peters, D. K., Lachmann, P. J. 1974. Immunity deficiency in pathogenesis of glomerulonephritis. Lancet, i, 58.CrossRefGoogle Scholar
  41. Peters, D. K., Williams, D. G. 1974. Complement and mesangiocapillary glomerulonephritis. Role of complement deficiency in the pathogenesis of nephritis. Nephron, 13, 189.CrossRefGoogle Scholar
  42. Petty, R. E., Steward, M. W., Soothill, J. F. 1972. The heterogeneity of antibody affinity in inbred mice and its possible immunopathological significance. Clin Exp. Immunol., 12, 231.PubMedGoogle Scholar
  43. Pollak, V. E., Pirani, C. L., Dujovne, I., Dillard, M. G. 1973. The clinical course of lupus nephritis: relationship to the renal histologic findings. In: Glomerulonephritis. Eds. Kincaid-Smith, P., Mathew, T. K., Becker, E. L. John Wiley, New York, p. 1167.Google Scholar
  44. Report of the International Study of kidney disease in children. 1974. Lancet, ii, 423.Google Scholar
  45. Shahloub, R. J. 1974. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet, ii, 556.CrossRefGoogle Scholar
  46. Sirinha, S., Suskind, R., Edelman, R., Charupatana, C., Olson, R. E. 1973. Complement and C3-proactivator levels in children with protein-calorie malnutrition and effect of dietary treatment. Lancet, i, 1016.CrossRefGoogle Scholar
  47. Sitprija, V., Pipatnagul, V., Boonpucknavig, V., Boonpucknavig, S. 1974. Glomerulonephritis in typhoid fever. Ann. Int. Med., 81, 210.PubMedGoogle Scholar
  48. Soothill, J. F., Steward, M. W. 1971. The immuno-pathological significance of the heterogeneity of antibody affinity. Clin. Exp. Immunol., 9, 196.Google Scholar
  49. Steinberg, A. D., Kaltreider, H. B., Staples, P. J., Goeztri, E. J., Talal, N., Decker, J. L. 1973. Cyclophosphamide in lupus nephritis: a controlled trial. Ann. Int. Med., 75, 165.Google Scholar
  50. Sztejnbok, M., Stewart, A., Diamond, H., Kaplan, D. 1971. Azathioprine in the treatment of systemic lupus erythematosus. A controlled study. Arthr. Rheum., 14, 639.CrossRefGoogle Scholar
  51. Talal, N., Bunim, J. J. 1964. The development of malignant lymphoma in the course of Sjogren’s syndrome. Amer. J. Med., 36, 529.PubMedCrossRefGoogle Scholar
  52. Talal, N. 1970. Immunologic and viral factors in the pathogenesis of systemic lupus erythematosus. Arthr. Rheum., 13, 887.CrossRefGoogle Scholar
  53. Tannenbaum, H., Schur, P. H. 1974. Development of reticulum cell sarcoma during cyclophosphamide therapy. Arthr. Rheum., 17, 15.CrossRefGoogle Scholar
  54. Tenth report of the Human Renal Transplant Registry. 1972. J. Amer. Med. Ass., 221, 1495.Google Scholar
  55. Vassali, P., McCluskey, R. T. 1971. Role of coagulation processes in immunologic glomerular diseases. Advances in Nephrology, 1, 55.Google Scholar
  56. Walker, S. E., Bole, G. G. 1973. Augmented incidence of neoplasia in NZB/NZW mice treated with long-term cyclophosphamide. J. Lab. Clin. Med., 82, 619.PubMedGoogle Scholar
  57. Wardle, D. V. 1974. Reticuloendothelial clearance studies in the course of horse serum induced nephritis. Brit. J. Exp. Path. 55, 149.PubMedGoogle Scholar
  58. White, R. H. R., Glasgow, E. F. C., Mills, R. J. 1971. Clinicopathological study of the nephrotic syndrome in childhood. Lancet, i, 1353.Google Scholar
  59. Wood, L. 1974. Cyclophosphamide and neoplasia (letter). Lancet, ii, 898.CrossRefGoogle Scholar
  60. W.H.O. memorandum no. 394. 1971. W.H.O., Geneva.Google Scholar
  61. W.H.O. Report No. 544. 1972. A survey of nutritional-immunological interactions. Bull. W.H.O., 46, 537.Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • J. S. Cameron
    • 1
  1. 1.Renal MedicineGuy’s HospitalLondon

Personalised recommendations