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Immunosuppressive Therapy of Proliferative Glomerulonephritis in Children FREE

Rodrigo E. Urizar, MD; Birger Tinglof, MD; Rawle McIntosh, MD; Neil Litman, MD; Eugene Barnett, MD; James Wilkerson, MD; Fred Smith, MD; Robert L. Vernier, MD
[+] Author Affiliations

Received for publication May 29, 1968.

Read in part before the Third International Congress of Nephrology, Washington, DC, September 1966.

Reprint requests to the Department of Pediatrics, University of Minnesota, 1460 Mayo Memorial Bldg, Minneapolis 55455 (Dr. Vernier).


Am J Dis Child. 1969;118(3):411-425. doi:10.1001/archpedi.1969.02100040413001.
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THE VARIOUS forms of proliferative glomerulonephritis, with or without the nephrotic syndrome, are difficult therapeutic challenges and with few exceptions lead inexorably to renal failure. Excluded from consideration are patients with acute poststreptococcal glomerulonephritis in whom complete recovery usually occurs without specific therapy2 and a high percentage of patients with the nephrotic syndrome of childhood who respond to adrenocortical steroid management.3 Some patients with severe lupus glomerulonephritis may recover normal renal function and nearlynormal morphology after intensive treatment with corticosteroids,4,5 although the incidence of serious complications remains high.

Involvement of immune processes in the pathogenesis of glomerulonephritis is supported by a large body of information collected during the past 50 years.6 The more recent availability of serial renal biopsy specimens and improved morphologic techniques, particularly immunofluorescence and electron microscopy, together with the measurement of serum immunoglobulins, have further emphasized the probable pathogenic role of immune mechanisms

REFERENCES

Vernier, R.L., et al: Immunofluorescence Studies in Renal Disease, Proceedings of the Third International Congress of Nephrology , Washington, New York: S. Karger, (September) 1967;, vol 3, pp 83-94.
Perlman, L.V., et al:  Post-Streptococcal Glomerulonephritis: A Ten Year Follow-up of an Epidemic , JAMA 194:63-70 ( (Oct 4) ) 1965;.
Cornfield, D., and Schwartz, M.W.:  Nephrosis: A Long Term Study of Children Treated With Corticosteroids , J Pediat 68:507-515 ( (April) ) 1966;.
Pollack, V.E.; Pirani, C.L.; and Kark, R.M.:  Effect of Large Doses of Prednisone on the Renal Lesions and Life Span of Patients With Lupus Glomerulonephritis , J Lab Clin Med 57:495-511 ( (April) ) 1961;.
Smith, F.G.; Litman, N.; and Latta, H.:  Lupus Glomerulonephritis: The Effect of Large Doses of Corticosteroids on Renal Function and Renal Lesions in Two Children , Amer J Dis Child 110:302-308 ( (Sept) ) 1965;.
Michael, A.F., et al:  Immunological Basis of Renal Disease , Pediat Clin N Amer 11:685-721 ( (Aug) ) 1965;.
Unanue, E.R., and Dixon, F.J., Jr.:  "Experimental Glomerulonephritis: Immunological Events and Pathological Mechanisms,"  in Dixon, F.J., Jr., and Humphrey, J.H. (eds.): Advances of Immunology , New York: Academic Press, Inc., 1967;, pp 1-90.
Chasis, H.; Goldring, W.; and Baldwin, D.S.:  Effect of Febrile Plasma Typhoid Vaccine and Nitrogen Mustard on Renal Manifestation of Human Glomerulonephritis , Proc Soc Exp Biol Med 71: 565-567 ( (Aug) ) 1949;.
Bariety, J., et al:  Les agents alkylants et les antimetabolites dans les glomerulopathies. Resultats en fonction du type histologique , Bull Soc Med Hop Paris 117:963-984 ( (Oct) ) 1966;.
White, R.H.R.; Cameron, J.S.; and Trounce, J.R.:  Immunosuppressive Therapy in Steroid-Resistant Proliferative Glomerulonephritis Accompanied by the Nephrotic Syndrome , Brit Med J 2: 853-860 ( (Oct) ) 1966;.
Michael, A.F., et al:  Immunosuppressive Therapy of Chronic Renal Disease , New Eng J Med 276: 817-828 ( (April) ) 1967;.
West, C.D., et al:  Immunosuppressive Therapy in Resistant Hypocomplementemic Glomerulonephritis and in Lupus Nephritis , J Pediat 67:1113-1122 ( (Dec) ) 1965;.
Grupe, W.E., and Heymann, W.:  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 , Amer J Dis Child 112:448-458 ( (Nov) ) 1966;.
Shearn, M.A.:  Mercaptopurine in the Treatment of Steroid-Resistant Nephrotic Syndrome , New Eng J Med 273:943-947 ( (Oct) ) 1965;.
Goodman, H.C., et al:  Current Studies of the Effect of Antimetabolites in Nephrosis, Other Non-Neoplastic Diseases and Experimental Animals, Combined Clinical Staff Conference at the National Institutes of Health , Ann Intern Med 59:388-407 ( (Sept) ) 1963;.
Miescher, P.A., and Riethmüller, D.:  Diagnosis and Treatment of Systemic Lupus Erythematosus , Seminars Hemat 2:1-28 ( (Jan) ) 1965;.
Swanson, M.A., and Schwartz, R.S.:  Immunosuppressive Therapy: The Relation Between Clinical Response and Immunologic Competence , New Eng J Med 277:163-170 ( (July) ) 1967;.
Fahey, J.L., and McKelvey, E.M.:  Quantitative Determination of Serum Immunoglobulins in Antibody-Agar Plates , J Immun 94:84-90 ( (Jan) ) 1965;.
Kabat, E.A., and Mayer, M.M.: Experimental Immunochemistry , ed 2, Springfield, Ill: Charles C Thomas, Publisher, 1964;, p 149.
Klemperer, M.E., et al:  Estimation of the Serum Beta-1-C Globulin Concentration: Its Relation to the Serum Hemolytic Complement Titer , Pediatrics 35:765-769 ( (May) ) 1965;.
Barnett, E.V., et al:  Antinuclear Factors in Systemic Lupus Erythematosus and Rheumatoid Arthritis , Ann Intern Med 63:100-108 ( (July) ) 1965;.
Pirani, C.L.; Pollack, V.E.; and Schwartz, F.D.:  The Reproducibility of Semiquantitative Analyses of Renal Histology , Nephron 1:230-237, 1964;.
Michael, A.F., et al:  Acute Post-Streptococcal Glomerulonephritis: Immune Deposit Disease , J Clin Invest 45:237-248 ( (Feb) ) 1966;.
Feldman, J.D.; Mardiney, M.R.; and Shuler, S.E.:  Immunology and Morphology of Acute Post-Streptococcal Glomerulonephritis , Lab Invest 15: 283-301 ( (Jan) , pt 2) 1966;.
Kunkel, H.G.:  Mechanisms of Renal Injury in Systemic Lupus Erythematosus , Arthritis Rheum 9: 725-727 ( (Oct) ) 1966;.
Seegal, B.C., et al:  Studies on the Pathogenesis of Acute and Progressive Glomerulonephritis in Man by Immunofluorescein and Immunoferritin Techniques , Fed Proc 24:100-108 ( (Jan) -Feb) 1965;.
Duncan, D.A., et al:  Pulmonary Hemorrhage and Glomerulonephritis: Report of Six Cases and Study of the Renal Lesion by the Fluorescent Antibody Technique and Electron Microscopy , Ann Intern Med 62:920-938 ( (May) ) 1965;.
Lerner, R.A.; Glassock, R.J.; and Dixon, F.J.:  The Role of Antiglomerular Basement Membrane Antibody in the Pathogenesis of Human Glomerulonephritis , J Exp Med 126:989-1004 ( (Dec) ) 1967;.
Murray, J.E., et al:  Prolonged Survival of Human Kidney Homografts by Immunosuppressive Drug Therapy , New Eng J Med 268:1315-1323 ( (June) ) 1963;.
Levin, R.H.; Landy, M.; and Frei, E.:  The Effect of 6-Mercaptopurine on Immune Response in Man , New Eng J Med 271:16-22 ( (July) ) 1964;.
Corley, C.; Lessner, H.; and Larsen, W.E.:  Azathioprine Therapy of Autoimmune Diseases , Amer J Med 41:404-412 ( (Sept) ) 1966;.
Kobayashi, O., and Wada, H.:  Needle Renal Biopsy of Healed Acute Glomerulonephritis in Children , Acta Med Biol 9:117-122, 1961;.
Vernier, R.L.; Worthen, H.G.; and Good, R.A.:  The Pathology of the Nephrotic Syndrome , J Pediat 48:620-639 ( (May) ) 1961;.
Baker, B.L.: Modification of Body Structure by Adrenocortical Secretions With Special Reference to Growth: In Pituitary-Adrenal Function , R. C. Christman (ed.), Washington, DC: American Association for the Advancement of Science, 1950;, p 88-95.
Adams, D.A.; Maxwell, M.H.; and Bernstein, D.:  Corticosteroid Therapy of Glomerulonephritis and the Nephrotic Syndrome , J Chronic Dis 15: 29-50 ( (Jan) ) 1962;.
Page, A.R.; Condie, R.M.; and Good, R.A.:  Effect of 6-Mercaptopurine on Inflammation , Amer J Path 40:519-530 ( (May) ) 1962;.
Schwartz, R.; Stack, J.; and Dameshek, W.:  Effect of 6-Mercaptopurine on Antibody Production , Proc Soc Exp Biol Med 99:164-167 ( (Oct) ) 1958;.
Bole, G.C., and Heath, L.E.:  The Effect of 6-Mercaptopurine on the Inflammatory Response Stimulated by Subcutaneous Implantations of Polyvinyl Sponge , Arthritis Rheum 10:377-387 ( (Aug) ) 1967;.
Kelley, W.N.; Rosenbloom, F.M.; and Seegmiller, J.E.:  The Effects of Azathioprine (Imuran) on Purine Synthesis in Clinical Disorders of Purine Metabolism , J Clin Invest 46:1518-1529 ( (Sept) ) 1967;.
Lange, K., et al:  Steroid Therapy of Systemic Lupus Erythematosus Based on Immunologic Considerations , Arthritis Rheum 8:244-259 ( (April) ) 1965;.
Stickler, G.B.; Burke, E.C.; and McKenzie, B.F.:  Electrophoretic Studies of the Nephrotic Syndrome in Children: Preliminary Report , Mayo Proc Clin 29:555-561 ( (Oct) ) 1954;.
West, C.D.; Northway, J.D.; and Davis, N.C.:  Serum Levels of Beta-1-C Globulin, a Complement Component in the Nephritides, Lipoid Nephrosis and Other Conditions , J Clin Invest 43:1507-1517 ( (Aug) ) 1964;.
Wintrobe, M.M.: Clinical Hematology , ed 5, Philadelphia: Lea & Febiger, 1961;, p 240.

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References

Vernier, R.L., et al: Immunofluorescence Studies in Renal Disease, Proceedings of the Third International Congress of Nephrology , Washington, New York: S. Karger, (September) 1967;, vol 3, pp 83-94.
Perlman, L.V., et al:  Post-Streptococcal Glomerulonephritis: A Ten Year Follow-up of an Epidemic , JAMA 194:63-70 ( (Oct 4) ) 1965;.
Cornfield, D., and Schwartz, M.W.:  Nephrosis: A Long Term Study of Children Treated With Corticosteroids , J Pediat 68:507-515 ( (April) ) 1966;.
Pollack, V.E.; Pirani, C.L.; and Kark, R.M.:  Effect of Large Doses of Prednisone on the Renal Lesions and Life Span of Patients With Lupus Glomerulonephritis , J Lab Clin Med 57:495-511 ( (April) ) 1961;.
Smith, F.G.; Litman, N.; and Latta, H.:  Lupus Glomerulonephritis: The Effect of Large Doses of Corticosteroids on Renal Function and Renal Lesions in Two Children , Amer J Dis Child 110:302-308 ( (Sept) ) 1965;.
Michael, A.F., et al:  Immunological Basis of Renal Disease , Pediat Clin N Amer 11:685-721 ( (Aug) ) 1965;.
Unanue, E.R., and Dixon, F.J., Jr.:  "Experimental Glomerulonephritis: Immunological Events and Pathological Mechanisms,"  in Dixon, F.J., Jr., and Humphrey, J.H. (eds.): Advances of Immunology , New York: Academic Press, Inc., 1967;, pp 1-90.
Chasis, H.; Goldring, W.; and Baldwin, D.S.:  Effect of Febrile Plasma Typhoid Vaccine and Nitrogen Mustard on Renal Manifestation of Human Glomerulonephritis , Proc Soc Exp Biol Med 71: 565-567 ( (Aug) ) 1949;.
Bariety, J., et al:  Les agents alkylants et les antimetabolites dans les glomerulopathies. Resultats en fonction du type histologique , Bull Soc Med Hop Paris 117:963-984 ( (Oct) ) 1966;.
White, R.H.R.; Cameron, J.S.; and Trounce, J.R.:  Immunosuppressive Therapy in Steroid-Resistant Proliferative Glomerulonephritis Accompanied by the Nephrotic Syndrome , Brit Med J 2: 853-860 ( (Oct) ) 1966;.
Michael, A.F., et al:  Immunosuppressive Therapy of Chronic Renal Disease , New Eng J Med 276: 817-828 ( (April) ) 1967;.
West, C.D., et al:  Immunosuppressive Therapy in Resistant Hypocomplementemic Glomerulonephritis and in Lupus Nephritis , J Pediat 67:1113-1122 ( (Dec) ) 1965;.
Grupe, W.E., and Heymann, W.:  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 , Amer J Dis Child 112:448-458 ( (Nov) ) 1966;.
Shearn, M.A.:  Mercaptopurine in the Treatment of Steroid-Resistant Nephrotic Syndrome , New Eng J Med 273:943-947 ( (Oct) ) 1965;.
Goodman, H.C., et al:  Current Studies of the Effect of Antimetabolites in Nephrosis, Other Non-Neoplastic Diseases and Experimental Animals, Combined Clinical Staff Conference at the National Institutes of Health , Ann Intern Med 59:388-407 ( (Sept) ) 1963;.
Miescher, P.A., and Riethmüller, D.:  Diagnosis and Treatment of Systemic Lupus Erythematosus , Seminars Hemat 2:1-28 ( (Jan) ) 1965;.
Swanson, M.A., and Schwartz, R.S.:  Immunosuppressive Therapy: The Relation Between Clinical Response and Immunologic Competence , New Eng J Med 277:163-170 ( (July) ) 1967;.
Fahey, J.L., and McKelvey, E.M.:  Quantitative Determination of Serum Immunoglobulins in Antibody-Agar Plates , J Immun 94:84-90 ( (Jan) ) 1965;.
Kabat, E.A., and Mayer, M.M.: Experimental Immunochemistry , ed 2, Springfield, Ill: Charles C Thomas, Publisher, 1964;, p 149.
Klemperer, M.E., et al:  Estimation of the Serum Beta-1-C Globulin Concentration: Its Relation to the Serum Hemolytic Complement Titer , Pediatrics 35:765-769 ( (May) ) 1965;.
Barnett, E.V., et al:  Antinuclear Factors in Systemic Lupus Erythematosus and Rheumatoid Arthritis , Ann Intern Med 63:100-108 ( (July) ) 1965;.
Pirani, C.L.; Pollack, V.E.; and Schwartz, F.D.:  The Reproducibility of Semiquantitative Analyses of Renal Histology , Nephron 1:230-237, 1964;.
Michael, A.F., et al:  Acute Post-Streptococcal Glomerulonephritis: Immune Deposit Disease , J Clin Invest 45:237-248 ( (Feb) ) 1966;.
Feldman, J.D.; Mardiney, M.R.; and Shuler, S.E.:  Immunology and Morphology of Acute Post-Streptococcal Glomerulonephritis , Lab Invest 15: 283-301 ( (Jan) , pt 2) 1966;.
Kunkel, H.G.:  Mechanisms of Renal Injury in Systemic Lupus Erythematosus , Arthritis Rheum 9: 725-727 ( (Oct) ) 1966;.
Seegal, B.C., et al:  Studies on the Pathogenesis of Acute and Progressive Glomerulonephritis in Man by Immunofluorescein and Immunoferritin Techniques , Fed Proc 24:100-108 ( (Jan) -Feb) 1965;.
Duncan, D.A., et al:  Pulmonary Hemorrhage and Glomerulonephritis: Report of Six Cases and Study of the Renal Lesion by the Fluorescent Antibody Technique and Electron Microscopy , Ann Intern Med 62:920-938 ( (May) ) 1965;.
Lerner, R.A.; Glassock, R.J.; and Dixon, F.J.:  The Role of Antiglomerular Basement Membrane Antibody in the Pathogenesis of Human Glomerulonephritis , J Exp Med 126:989-1004 ( (Dec) ) 1967;.
Murray, J.E., et al:  Prolonged Survival of Human Kidney Homografts by Immunosuppressive Drug Therapy , New Eng J Med 268:1315-1323 ( (June) ) 1963;.
Levin, R.H.; Landy, M.; and Frei, E.:  The Effect of 6-Mercaptopurine on Immune Response in Man , New Eng J Med 271:16-22 ( (July) ) 1964;.
Corley, C.; Lessner, H.; and Larsen, W.E.:  Azathioprine Therapy of Autoimmune Diseases , Amer J Med 41:404-412 ( (Sept) ) 1966;.
Kobayashi, O., and Wada, H.:  Needle Renal Biopsy of Healed Acute Glomerulonephritis in Children , Acta Med Biol 9:117-122, 1961;.
Vernier, R.L.; Worthen, H.G.; and Good, R.A.:  The Pathology of the Nephrotic Syndrome , J Pediat 48:620-639 ( (May) ) 1961;.
Baker, B.L.: Modification of Body Structure by Adrenocortical Secretions With Special Reference to Growth: In Pituitary-Adrenal Function , R. C. Christman (ed.), Washington, DC: American Association for the Advancement of Science, 1950;, p 88-95.
Adams, D.A.; Maxwell, M.H.; and Bernstein, D.:  Corticosteroid Therapy of Glomerulonephritis and the Nephrotic Syndrome , J Chronic Dis 15: 29-50 ( (Jan) ) 1962;.
Page, A.R.; Condie, R.M.; and Good, R.A.:  Effect of 6-Mercaptopurine on Inflammation , Amer J Path 40:519-530 ( (May) ) 1962;.
Schwartz, R.; Stack, J.; and Dameshek, W.:  Effect of 6-Mercaptopurine on Antibody Production , Proc Soc Exp Biol Med 99:164-167 ( (Oct) ) 1958;.
Bole, G.C., and Heath, L.E.:  The Effect of 6-Mercaptopurine on the Inflammatory Response Stimulated by Subcutaneous Implantations of Polyvinyl Sponge , Arthritis Rheum 10:377-387 ( (Aug) ) 1967;.
Kelley, W.N.; Rosenbloom, F.M.; and Seegmiller, J.E.:  The Effects of Azathioprine (Imuran) on Purine Synthesis in Clinical Disorders of Purine Metabolism , J Clin Invest 46:1518-1529 ( (Sept) ) 1967;.
Lange, K., et al:  Steroid Therapy of Systemic Lupus Erythematosus Based on Immunologic Considerations , Arthritis Rheum 8:244-259 ( (April) ) 1965;.
Stickler, G.B.; Burke, E.C.; and McKenzie, B.F.:  Electrophoretic Studies of the Nephrotic Syndrome in Children: Preliminary Report , Mayo Proc Clin 29:555-561 ( (Oct) ) 1954;.
West, C.D.; Northway, J.D.; and Davis, N.C.:  Serum Levels of Beta-1-C Globulin, a Complement Component in the Nephritides, Lipoid Nephrosis and Other Conditions , J Clin Invest 43:1507-1517 ( (Aug) ) 1964;.
Wintrobe, M.M.: Clinical Hematology , ed 5, Philadelphia: Lea & Febiger, 1961;, p 240.

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