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Cytotoxic Drugs in Steroid-Resistant Renal Disease: Alkylating and Antimetabolic Agents in the Treatment of Nephrotic Syndrome, Lupus Nephritis, Chronic Glomerulonephritis, and Purpura Nephritis in Children

Cytotoxic Drugs in Steroid-Resistant Renal Disease: Alkylating and Antimetabolic Agents in the... Abstract THE USE of cytotoxic agents in the treatment of renal diseases was first reported in 1949 by Chasis1,2 using nitrogen mustard (mechlorethamine) in adults with chronic glomerulonephritis. Shortly thereafter, Kelley and Panos3 confirmed improvement in children with nephrosis, and Taylor4 in adults with chronic glomerulonephritis, using the same approach. These reports were followed by others,5-9 but as the therapeutic value of steroids became more widely accepted, cytotoxic drugs were displaced as therapeutic agents. Interest was renewed in 1963 by Coldbeck,10 Kellum and Haserick,11 and Goodman and Wolff.12 There has been further encouragement in the use of these agents in the treatment of other nonneoplastic diseases12-15 as well as in renal diseases.15-22 This report will review 3½ years' experience in 25 children with cytotoxic drugs in addition to corticosteroids in the treatment of chronic renal diseases. Patients and Methods The agents used References 1. Chasis, H.; Goldring, W.; and Baldwin, D.S.: Effect of Febrile Plasma, Typhoid Vaccine and Nitrogen Mustard on Renal Manifestations of Human Glomerulonephritis , Proc Soc Exp Biol Med 71:565, 1949.Crossref 2. Baldwin, D.S.; McLean, P.G.; Chasis, H.; and Goldring, W.: Effect of Nitrogen Mustard on the Clinical Course of Glomerulonephritis , Arch Intern Med 92:162, 1953.Crossref 3. Kelley, V.C., and Panos, T.C.: Nephrotic Syndrome in Children: I. Clinical Response to Nitrogen Mustard Therapy , J Pediat 41:505, 1952.Crossref 4. Taylor, R.D.; Corcoran, A.C.; and Page, I.H.: Treatment of the Nephrotic Syndrome With Nitrogen Mustard , J Lab Clin Med 36:996, 1950. 5. Boyd, R.I., and Commons, R.R.: Effect of Nitrogen Mustard Upon Chronic Glomerulonephritis , Amer J Med 13:499, 1952.Crossref 6. Lestina, F.A.; Freeman, S.; and Wilson, H.: Treatment of the Nephrotic Syndrome With Nitrogen Mustard and ACTH , J Lab Clin Med 42:918, 1953. 7. Startzman, V., in Metcoff, J. (ed.): Proceedings of the Sixth Annual Conference on the Nephrotic Syndrome, p 247,1954. 8. Greenman, L.; Weigand, F.A.; and Danowski, T.S.: Therapy of the Nephrotic Syndrome , Amer J Dis Child 89:169, 1955. 9. West, C.D.: Use of Combined Hormone and Mechlorethamine (Nitrogen Mustard) Therapy in Lipoid Nephrosis , Amer J Dis Child 95:498, 1958. 10. Coldbeck, J.H.: Experience With Alkylating Agents in the Treatment of Children With the Nephrotic Syndrome , Med J Aust 2:987, 1963. 11. Kellum, R.E., and Haserick, J.R.: Mechlorethamine Therapy for Systemic Lupus Nephropathy , Arch Derm 87:289, 1963.Crossref 12. Goodman, H.C., et al: Current Studies on the Effect of Antimetabolites in Nephrosis, Other Non-neoplastic Diseases, and Experimental Animals , Ann Intern Med 59:388, 1963.Crossref 13. Eisen, B.; Demis, D.J.; and Crosby, W.M.: Thioguanine Therapy: Systemic Lupus Erythematosus, Atopic Dermatitis and Other Non-Malignant Diseases , JAMA 179:789, 1962.Crossref 14. Lee, S.L., et al: Effect of 6-Mercaptopurine Administration on Antibody Production and Clinical Course in Systemic Lupus Erythematosus: Report of a Case , Arthritis Rheum 4:56,1961.Crossref 15. Demis, D.J.; Brown, C.S.; and Crosby, W.M.: Thioguanine in Treatment of Certain Autoimmune, Immunologic and Related Diseases , Amer J Med 37: 195, 1964.Crossref 16. Lagrue, G., et al: Résultats de la Chimothérapie Prolongée Au Cours de Certains Syndromes Néphrotiques , J Urol Nephrol 70:156, 1964. 17. Lagrue, G.; Bariéty, J.; and Milliez, P.: Moutards Azotées et Antimetabolites dans le Traitement des Syndromes Néphrotiques et de Certaines Nephropathies Glomérulaires , Actualités Néphrologiques 1:219, 1964. 18. Lagrue, G.: Le Moutards Azotées et les Antimetabolites dans le Traitement de Certaines Néphropathies Glomérulaires , Vie Méd 45:22, 1964. 19. Payet, M.: Treatment of Nephrotic Syndrome in Adult Africans With Cyclophosphamide , Therapie 19:921, 1964. 20. Talamo, R.C., and Crawford, J.D.: Trimethadione Nephrosis Treated With Cortisone and Nitrogen Mustard , New Eng J Med 269:15, 1963.Crossref 21. Shearn, M.A.: Mercaptopurine in the Treatment of Steroid-Resistant Nephrotic Syndrome , New Eng J Med 273:943, 1965.Crossref 22. West, C.D., et al: Immunosuppressive Therapy in Persistent Hypocomplementemic Glomerulonephritis and in Lupus Nephritis , J Pediat 67:1113, 1965.Crossref 23. Heymann, W., and Hunter, J.L.P.: Importance of Early Treatment of the Nephrotic Syndrome , JAMA 175:563, 1961.Crossref 24. Wheeler, G.P.: Studies Related to the Mechanisms of Action of Cytotoxic Alkylating Agents: A Review , Cancer Res 22:651,1962. 25. Schwartz, R.; Stack, J.; and Dameshek, W.: Effect of 6-Mercaptopurine on Antibody Production , Proc Soc Exp Biol Med 99:164, 1958.Crossref 26. Schwartz, R.; Eisner, A.; and Dameshek, W.: Effect of 6-Mercaptopurine on Primary and Secondary Immune Responses , J Clin Invest 38:1394, 1959.Crossref 27. Friedman, R.M.; Buckler, C.E.; and Baron, S.: The Effect of Aminomethylpteroylglutamic Acid on the Development of Skin Hypersensitivity and on Antibody Formation in Guinea Pigs , J Exp Med 114: 173, 1961.Crossref 28. Hoyer, J.R., et al: The Effect of 6-Mercaptopurine on Delayed Hypersensitivity in Guinea Pigs , J Exp Med 116:679, 1962.Crossref 29. Meeker, W., et al: Prolongation of Skin Homograft Survival in Rabbits by 6-Mercaptopurine , Proc Soc Exp Biol Med 102:459, 1959.Crossref 30. Calne, R.Y.: Rejection of Renal Homografts Inhibition in Dogs by 6-Mercaptopurine , Lancet 1: 417, 1960.Crossref 31. Dameshek, W., and Schwartz, R.: Treatment of Certain "Autoimmune" Diseases With Antimetabolites: Preliminary Report , Trans Assoc Amer Physicians 73:113, 1960. 32. Hoyer, L.W.; Good, R.A.; and Condie, R.M.: Experimental Allergic Encephalomyelitis: The Effect of 6-Mercaptopurine , J Exp Med 116:311, 1962.Crossref 33. Brandriss, M.W.: Methotrexate: Suppression of Experimental Allergic Encephalomyelitis , Science 140:186, 1963.Crossref 34. Lange, K.: Immunologic Basis of Glomerulonephritis and Nephrotic Syndrome , New York J Med 57:2095, 1957. 35. Heymann, W.: Pathogenesis of the Nephrotic Syndrome: Considerations Based on Clinical and Experimental Studies , J Pediat 58:609, 1961.Crossref 36. Page, A.R.; Condie, R.M.; and Good, R.A.: Clinical Studies on the Anti-Inflammatory Activity of 6-Mercaptopurine , Blood 20:118, 1962. 37. Page, A.R.; Condie, R.M.; and Good, R.A.: Suppression of Plasma Cell Hepatitis With 6-Mercaptopurine , Amer J Med 36:200, 1964.Crossref 38. Page, A.R.; Condie, R.M.; and Good, R.A.: Effect of 6-Mercaptopurine on Inflammation , Amer J Path 40:519, 1962. 39. Page, A.R.: Inhibition of the Lymphocyte Response to Inflammation With Antimetabolites , Amer J Path 45:1029, 1964. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Cytotoxic Drugs in Steroid-Resistant Renal Disease: Alkylating and Antimetabolic Agents in the Treatment of Nephrotic Syndrome, Lupus Nephritis, Chronic Glomerulonephritis, and Purpura Nephritis in Children

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Publisher
American Medical Association
Copyright
Copyright © 1966 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1966.02090140120011
Publisher site
See Article on Publisher Site

Abstract

Abstract THE USE of cytotoxic agents in the treatment of renal diseases was first reported in 1949 by Chasis1,2 using nitrogen mustard (mechlorethamine) in adults with chronic glomerulonephritis. Shortly thereafter, Kelley and Panos3 confirmed improvement in children with nephrosis, and Taylor4 in adults with chronic glomerulonephritis, using the same approach. These reports were followed by others,5-9 but as the therapeutic value of steroids became more widely accepted, cytotoxic drugs were displaced as therapeutic agents. Interest was renewed in 1963 by Coldbeck,10 Kellum and Haserick,11 and Goodman and Wolff.12 There has been further encouragement in the use of these agents in the treatment of other nonneoplastic diseases12-15 as well as in renal diseases.15-22 This report will review 3½ years' experience in 25 children with cytotoxic drugs in addition to corticosteroids in the treatment of chronic renal diseases. Patients and Methods The agents used References 1. Chasis, H.; Goldring, W.; and Baldwin, D.S.: Effect of Febrile Plasma, Typhoid Vaccine and Nitrogen Mustard on Renal Manifestations of Human Glomerulonephritis , Proc Soc Exp Biol Med 71:565, 1949.Crossref 2. Baldwin, D.S.; McLean, P.G.; Chasis, H.; and Goldring, W.: Effect of Nitrogen Mustard on the Clinical Course of Glomerulonephritis , Arch Intern Med 92:162, 1953.Crossref 3. Kelley, V.C., and Panos, T.C.: Nephrotic Syndrome in Children: I. Clinical Response to Nitrogen Mustard Therapy , J Pediat 41:505, 1952.Crossref 4. Taylor, R.D.; Corcoran, A.C.; and Page, I.H.: Treatment of the Nephrotic Syndrome With Nitrogen Mustard , J Lab Clin Med 36:996, 1950. 5. Boyd, R.I., and Commons, R.R.: Effect of Nitrogen Mustard Upon Chronic Glomerulonephritis , Amer J Med 13:499, 1952.Crossref 6. Lestina, F.A.; Freeman, S.; and Wilson, H.: Treatment of the Nephrotic Syndrome With Nitrogen Mustard and ACTH , J Lab Clin Med 42:918, 1953. 7. Startzman, V., in Metcoff, J. (ed.): Proceedings of the Sixth Annual Conference on the Nephrotic Syndrome, p 247,1954. 8. Greenman, L.; Weigand, F.A.; and Danowski, T.S.: Therapy of the Nephrotic Syndrome , Amer J Dis Child 89:169, 1955. 9. West, C.D.: Use of Combined Hormone and Mechlorethamine (Nitrogen Mustard) Therapy in Lipoid Nephrosis , Amer J Dis Child 95:498, 1958. 10. Coldbeck, J.H.: Experience With Alkylating Agents in the Treatment of Children With the Nephrotic Syndrome , Med J Aust 2:987, 1963. 11. Kellum, R.E., and Haserick, J.R.: Mechlorethamine Therapy for Systemic Lupus Nephropathy , Arch Derm 87:289, 1963.Crossref 12. Goodman, H.C., et al: Current Studies on the Effect of Antimetabolites in Nephrosis, Other Non-neoplastic Diseases, and Experimental Animals , Ann Intern Med 59:388, 1963.Crossref 13. Eisen, B.; Demis, D.J.; and Crosby, W.M.: Thioguanine Therapy: Systemic Lupus Erythematosus, Atopic Dermatitis and Other Non-Malignant Diseases , JAMA 179:789, 1962.Crossref 14. Lee, S.L., et al: Effect of 6-Mercaptopurine Administration on Antibody Production and Clinical Course in Systemic Lupus Erythematosus: Report of a Case , Arthritis Rheum 4:56,1961.Crossref 15. Demis, D.J.; Brown, C.S.; and Crosby, W.M.: Thioguanine in Treatment of Certain Autoimmune, Immunologic and Related Diseases , Amer J Med 37: 195, 1964.Crossref 16. Lagrue, G., et al: Résultats de la Chimothérapie Prolongée Au Cours de Certains Syndromes Néphrotiques , J Urol Nephrol 70:156, 1964. 17. Lagrue, G.; Bariéty, J.; and Milliez, P.: Moutards Azotées et Antimetabolites dans le Traitement des Syndromes Néphrotiques et de Certaines Nephropathies Glomérulaires , Actualités Néphrologiques 1:219, 1964. 18. Lagrue, G.: Le Moutards Azotées et les Antimetabolites dans le Traitement de Certaines Néphropathies Glomérulaires , Vie Méd 45:22, 1964. 19. Payet, M.: Treatment of Nephrotic Syndrome in Adult Africans With Cyclophosphamide , Therapie 19:921, 1964. 20. Talamo, R.C., and Crawford, J.D.: Trimethadione Nephrosis Treated With Cortisone and Nitrogen Mustard , New Eng J Med 269:15, 1963.Crossref 21. Shearn, M.A.: Mercaptopurine in the Treatment of Steroid-Resistant Nephrotic Syndrome , New Eng J Med 273:943, 1965.Crossref 22. West, C.D., et al: Immunosuppressive Therapy in Persistent Hypocomplementemic Glomerulonephritis and in Lupus Nephritis , J Pediat 67:1113, 1965.Crossref 23. Heymann, W., and Hunter, J.L.P.: Importance of Early Treatment of the Nephrotic Syndrome , JAMA 175:563, 1961.Crossref 24. Wheeler, G.P.: Studies Related to the Mechanisms of Action of Cytotoxic Alkylating Agents: A Review , Cancer Res 22:651,1962. 25. Schwartz, R.; Stack, J.; and Dameshek, W.: Effect of 6-Mercaptopurine on Antibody Production , Proc Soc Exp Biol Med 99:164, 1958.Crossref 26. Schwartz, R.; Eisner, A.; and Dameshek, W.: Effect of 6-Mercaptopurine on Primary and Secondary Immune Responses , J Clin Invest 38:1394, 1959.Crossref 27. Friedman, R.M.; Buckler, C.E.; and Baron, S.: The Effect of Aminomethylpteroylglutamic Acid on the Development of Skin Hypersensitivity and on Antibody Formation in Guinea Pigs , J Exp Med 114: 173, 1961.Crossref 28. Hoyer, J.R., et al: The Effect of 6-Mercaptopurine on Delayed Hypersensitivity in Guinea Pigs , J Exp Med 116:679, 1962.Crossref 29. Meeker, W., et al: Prolongation of Skin Homograft Survival in Rabbits by 6-Mercaptopurine , Proc Soc Exp Biol Med 102:459, 1959.Crossref 30. Calne, R.Y.: Rejection of Renal Homografts Inhibition in Dogs by 6-Mercaptopurine , Lancet 1: 417, 1960.Crossref 31. Dameshek, W., and Schwartz, R.: Treatment of Certain "Autoimmune" Diseases With Antimetabolites: Preliminary Report , Trans Assoc Amer Physicians 73:113, 1960. 32. Hoyer, L.W.; Good, R.A.; and Condie, R.M.: Experimental Allergic Encephalomyelitis: The Effect of 6-Mercaptopurine , J Exp Med 116:311, 1962.Crossref 33. Brandriss, M.W.: Methotrexate: Suppression of Experimental Allergic Encephalomyelitis , Science 140:186, 1963.Crossref 34. Lange, K.: Immunologic Basis of Glomerulonephritis and Nephrotic Syndrome , New York J Med 57:2095, 1957. 35. Heymann, W.: Pathogenesis of the Nephrotic Syndrome: Considerations Based on Clinical and Experimental Studies , J Pediat 58:609, 1961.Crossref 36. Page, A.R.; Condie, R.M.; and Good, R.A.: Clinical Studies on the Anti-Inflammatory Activity of 6-Mercaptopurine , Blood 20:118, 1962. 37. Page, A.R.; Condie, R.M.; and Good, R.A.: Suppression of Plasma Cell Hepatitis With 6-Mercaptopurine , Amer J Med 36:200, 1964.Crossref 38. Page, A.R.; Condie, R.M.; and Good, R.A.: Effect of 6-Mercaptopurine on Inflammation , Amer J Path 40:519, 1962. 39. Page, A.R.: Inhibition of the Lymphocyte Response to Inflammation With Antimetabolites , Amer J Path 45:1029, 1964.

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: Nov 1, 1966

References