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January 1975, Vol 110, No. 1 >
ARTICLE | January 1975

Antilymphocyte Globulin in Renal Transplantation: Title and subTitle BreakNephrotic Syndrome and Infection as Possible Complications FREE

René P. Michel, MD; Ronald D. Guttmann, MD; Juergen Knaack, MD; John Klassen, MD; Jean-Guy Beaudoin, MD; Douglas D. Morehouse, MD
[+] Author Affiliations

Accepted for publication Aug 8, 1974.

Reprint requests to Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada (Dr. Guttmann).


Arch Surg. 1975;110(1):90-93. doi:10.1001/archsurg.1975.01360070090016
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During a two-year period, nine patients received equine antilymphocyte globulin (ALG) as part of their immunosuppressive therapy following cadaver renal transplantation. Of these, three patients (33%) developed nephrotic syndrome. A fourth patient had proteinuria greater than 3 gm/24 hr not attributable to recurrent disease or rejection. Of 32 other patients with cadaver renal allografts done during the same time, none had nephrotic syndrome and two (6%) had proteinuria greater than 3 gm/24 hr, both with biopsy evidence of rejection. This suggests an association between ALG therapy and risk for developing nephrotic syndrome, but the mechanism is not clear and deserves further investigation. During the first three months following transplantation, the nine patients treated with ALG had 20 infections, which seems to be more per patient than in our other transplant recipients.

REFERENCES

1 +
Starzl TE, Marchioro TL, Porter KA, et al:  The use of heterologous antilymphoid agents in canine renal and liver hemotransplantation and in human renal transplantation . Surg Gynecol Obstet 124:301-308, 1967;.
2 +
Collste LG:  Intravenous antilymphocyte globulin in human cadaveric renal transplantation: Clinical and immunologic observations . Acta Chir Scand 138:765-774, 1972;.
3 +
Traeger J, Touraine JL, Fries D, et al:  Evaluation of intravenous route for administration of antilymphocyte globulin in humans . Transplant Proc 3:749-753, 1971;.
4 +
Cosimi AB, Skameme E, Bonney WW, et al:  Experience with large-dose intravenous antithymocyte globulin in primates and man . Surgery 68:54-61, 1970;.
5 +
Davis RC, Nabseth DC, Olsson CA, et al:  Effect of rabbit ALG on cadaver kidney transplant survival . Ann Surg 176:521-528, 1972;.
6 +
Fries D, Blanc-Brunat N, Traeger J:  Pathology of renal allografts in patients receiving long-term antilymphocyte globulin therapy . Transplantation 10:20-32, 1970;.
7 +
Monaco AP, Wood ML, Van der Werf BA, et al:  Effect of antilymphocyte serum in mice, dogs and man . Ciba Found Study Group 29:111-138, 1967;.
8 +
Traeger J, Carraz M, Fries D, et al:  Studies of anti-lymphocyte globulins made from thoracic duct lymphocytes . Transplant Proc 1:455-459, 1969;.
9 +
Birtch AG, Carpenter CB, Tilney NL, et al:  Controlled clinical trial of antilymphocyte globulin in human renal allografts . Transplant Proc 3:762-765 1971;.
10 +
Deodhar SD, Konomi K, Nakamoto S, et al:  Clinical experience with antilymphocyte globulin (ALG) in renal transplantation . Transplant Proc 3:758-761, 1971;.
11 +
Wilson RE, Carpenter CB, Birtch AG, et al:  Peter Bent Brigham Hospital experience with controlled clinical trial of antilymphocyte globulin for human renal allografts , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 129-134.
12 +
Bach JF, Dardenne M, Galanaud P, et al:  Etude analytique de 69 sérums de lapin antilymphocytes de souris: I. Activités in vivo." Pathol Biol 18:471-478, 1970;.
13 +
Cohen BJ, De Vries MJ, Van Noord MJ, et al:  Strain-specific renal toxicity of heterologous antilymphocyte gamma globulin in mice . Transplantation 10:1-19, 1970;.
14 +
Denman AM, Russell AS, Denman EJ:  ALG and a model for auto-immunity , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 253-260.
15 +
Guttmann RD, Carpenter CB, Lindquist R, et al:  Treatment with heterologous antithymus sera: Nephritis associated with modification of renal allograft rejection and the immune status of the host to foreign protein . Transplantation 5:1115-1120, 1967;.
16 +
Lindquist RR, Guttmann RD, Carpenter CB, et al:  Nephritis induced by antilymphocyte serum: An electron microscopic and immunohistochemical study . Transplantation 8:545-557, 1969;.
17 +
Diethelm AG, Busch GJ, Dubernard JM, et al:  Prolongation of canine renal allografts by horse anti-dog lymphocyte serum and globulin . Ann Surg 169:569-577, 1969;.
18 +
Iwasaki Y, Porter KA, Amend J, et al:  The preparation and testing of horse antidog and antihuman antilymphoid plasma or serum and its protein fractions . Surg Gynecol Obstet 124:1-24, 1967;.
19 +
Chase WH, Paine LD, Lamoureux G, et al:  ultrastructural study of the glomerulonephritis produced by antilymphocyte globulin in monkeys . Lab Invest 27:393-399, 1972;.
20 +
Taylor HE:  The occurrence of glomerular basement membrane-reactive antibodies in antihuman antithymocyte globulin . Transplant Proc 2:413-416, 1970;.
21 +
Thiel G, Moppert J, Mahlich J, et al:  Glomerular damage after intravenous administration of antilymphocyte globulin (ALG) in man and rhesus monkeys . Transplant Proc 3:741-744, 1971;.
22 +
Wilson CB, Dixon FJ, Fortner JG, et al:  Glomerular basement membrane-reactive antibody in antilymphocyte globulin . J Clin Invest 50:1525-1535, 1971;.
23 +
Guttmann RD, Carpenter CB, Lindquist RR, et al:  Renal transplantation in the inbred rat: III. A study of heterologous antithymocyte sera . J Exp Med 126:1099-1127, 1967;.
24 +
Largiadèr F:  Results of AHLG-therapy in kidney allotransplantation , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 109-110.
25 +
Busch GJ, Kobayashi K, Birtch AG, et al:  Human renal allografts: Glomerular deposits of horse immunoglobulin G and nephritis following administration of antilymphocyte globulin . Hum Pathol 2:299-308, 1971;.
26 +
Thiel G, Gudat F, Moppert J, et al:  Follow-up of glomerular changes in man after intravenous administration of antilymphocyte globulin containing anti-glomerular-basement membrane antibodies (anti-GBM-Ab) , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 242-251.
27 +
Hirsh MS:  Effects of antilymphocytic serum on host responses to infectious agents . Fed Proc 29:169-170, 1970;.
28 +
Adamson DM, Cozad GC:  Effect of antilymphocyte serum on animals experimentally infected with Histoplasma capsulatum or Cryptococcus neoformans . J Bacteriol 100:1271-1276, 1969;.
29 +
Grogan JB:  Survival of Pseudomonas aeruginosa in the peritoneal cavity of mice treated with antilymphocyte serum . Arch Surg 105:460-463, 1972;.
30 +
Bach MC, Sahyoun A, Adler JL, et al:  Influence of rejection therapy on fungal and nocardial infections in renal-transplant recipients . Lancet 1:180-184, 1973;.
31 +
Monaco AP, Lewis EJ, Latzina A, et al:  Clinical use of equine anti-human lymph node lymphocyte serum: Preliminary results in 21 mismatched cadaveric renal transplants , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 355-362.
32 +
Taylor HE:  Clinical trial of antilymphocyte serum , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 343-348.
33 +
Epstein FH:  Nephrotic syndrome , in Wintrobe MM, Thorn GW, Adams RD, et al (eds): Harrison's Principles of Internal Medicine , ed 7. New York, McGraw-Hill Book Co Inc, 1974;, vol 2, p 1397.
34 +
Harlan WR Jr, Holden KR, Williams GM, et al:  Proteinuria and nephrotic syndrome associated with chronic rejection of kidney transplants . N Engl J Med 277:769-776, 1967;.
35 +
Hoyer JR, Raij L, Vernier RL, et al:  Recurrence of idiopathic nephrotic syndrome after renal transplantation . Lancet 2:343-348, 1972;.
36 +
Najarian JS, Foker JE:  Mechanisms of kidney allograft rejection . Transplant Proc 1:184-193, 1969;.
37 +
McCarthy LJ, Titus JL, Daugherty GW:  Bilateral renal-vein thrombosis and the nephrotic syndrome in adults . Ann Intern Med 58:837-857, 1963;.
38 +
Wilfert CM, Katz SL:  Etiology of bacterial sepsis in nephrotic children 1963-1967 . Pediatrics 42:840-843, 1968;.
39 +
Black JA, Challacombe DN, Ockenden BG:  Nephrotic syndrome associated with bacteremia after shunt operations for hydrocephalus . Lancet 2:921-924, 1965;.
40 +
Krebs RA, Burvant MU:  Nephrotic syndrome in association with varicella . JAMA 222:325-326, 1972;.

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1 +
Starzl TE, Marchioro TL, Porter KA, et al:  The use of heterologous antilymphoid agents in canine renal and liver hemotransplantation and in human renal transplantation . Surg Gynecol Obstet 124:301-308, 1967;.
2 +
Collste LG:  Intravenous antilymphocyte globulin in human cadaveric renal transplantation: Clinical and immunologic observations . Acta Chir Scand 138:765-774, 1972;.
3 +
Traeger J, Touraine JL, Fries D, et al:  Evaluation of intravenous route for administration of antilymphocyte globulin in humans . Transplant Proc 3:749-753, 1971;.
4 +
Cosimi AB, Skameme E, Bonney WW, et al:  Experience with large-dose intravenous antithymocyte globulin in primates and man . Surgery 68:54-61, 1970;.
5 +
Davis RC, Nabseth DC, Olsson CA, et al:  Effect of rabbit ALG on cadaver kidney transplant survival . Ann Surg 176:521-528, 1972;.
6 +
Fries D, Blanc-Brunat N, Traeger J:  Pathology of renal allografts in patients receiving long-term antilymphocyte globulin therapy . Transplantation 10:20-32, 1970;.
7 +
Monaco AP, Wood ML, Van der Werf BA, et al:  Effect of antilymphocyte serum in mice, dogs and man . Ciba Found Study Group 29:111-138, 1967;.
8 +
Traeger J, Carraz M, Fries D, et al:  Studies of anti-lymphocyte globulins made from thoracic duct lymphocytes . Transplant Proc 1:455-459, 1969;.
9 +
Birtch AG, Carpenter CB, Tilney NL, et al:  Controlled clinical trial of antilymphocyte globulin in human renal allografts . Transplant Proc 3:762-765 1971;.
10 +
Deodhar SD, Konomi K, Nakamoto S, et al:  Clinical experience with antilymphocyte globulin (ALG) in renal transplantation . Transplant Proc 3:758-761, 1971;.
11 +
Wilson RE, Carpenter CB, Birtch AG, et al:  Peter Bent Brigham Hospital experience with controlled clinical trial of antilymphocyte globulin for human renal allografts , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 129-134.
12 +
Bach JF, Dardenne M, Galanaud P, et al:  Etude analytique de 69 sérums de lapin antilymphocytes de souris: I. Activités in vivo." Pathol Biol 18:471-478, 1970;.
13 +
Cohen BJ, De Vries MJ, Van Noord MJ, et al:  Strain-specific renal toxicity of heterologous antilymphocyte gamma globulin in mice . Transplantation 10:1-19, 1970;.
14 +
Denman AM, Russell AS, Denman EJ:  ALG and a model for auto-immunity , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 253-260.
15 +
Guttmann RD, Carpenter CB, Lindquist R, et al:  Treatment with heterologous antithymus sera: Nephritis associated with modification of renal allograft rejection and the immune status of the host to foreign protein . Transplantation 5:1115-1120, 1967;.
16 +
Lindquist RR, Guttmann RD, Carpenter CB, et al:  Nephritis induced by antilymphocyte serum: An electron microscopic and immunohistochemical study . Transplantation 8:545-557, 1969;.
17 +
Diethelm AG, Busch GJ, Dubernard JM, et al:  Prolongation of canine renal allografts by horse anti-dog lymphocyte serum and globulin . Ann Surg 169:569-577, 1969;.
18 +
Iwasaki Y, Porter KA, Amend J, et al:  The preparation and testing of horse antidog and antihuman antilymphoid plasma or serum and its protein fractions . Surg Gynecol Obstet 124:1-24, 1967;.
19 +
Chase WH, Paine LD, Lamoureux G, et al:  ultrastructural study of the glomerulonephritis produced by antilymphocyte globulin in monkeys . Lab Invest 27:393-399, 1972;.
20 +
Taylor HE:  The occurrence of glomerular basement membrane-reactive antibodies in antihuman antithymocyte globulin . Transplant Proc 2:413-416, 1970;.
21 +
Thiel G, Moppert J, Mahlich J, et al:  Glomerular damage after intravenous administration of antilymphocyte globulin (ALG) in man and rhesus monkeys . Transplant Proc 3:741-744, 1971;.
22 +
Wilson CB, Dixon FJ, Fortner JG, et al:  Glomerular basement membrane-reactive antibody in antilymphocyte globulin . J Clin Invest 50:1525-1535, 1971;.
23 +
Guttmann RD, Carpenter CB, Lindquist RR, et al:  Renal transplantation in the inbred rat: III. A study of heterologous antithymocyte sera . J Exp Med 126:1099-1127, 1967;.
24 +
Largiadèr F:  Results of AHLG-therapy in kidney allotransplantation , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 109-110.
25 +
Busch GJ, Kobayashi K, Birtch AG, et al:  Human renal allografts: Glomerular deposits of horse immunoglobulin G and nephritis following administration of antilymphocyte globulin . Hum Pathol 2:299-308, 1971;.
26 +
Thiel G, Gudat F, Moppert J, et al:  Follow-up of glomerular changes in man after intravenous administration of antilymphocyte globulin containing anti-glomerular-basement membrane antibodies (anti-GBM-Ab) , in Seiler FR, Schwick HG (eds): ALG Therapy and Standardization Workshop . Marburg, Germany, Behringwerke AG, 1972;, vol 51, pp 242-251.
27 +
Hirsh MS:  Effects of antilymphocytic serum on host responses to infectious agents . Fed Proc 29:169-170, 1970;.
28 +
Adamson DM, Cozad GC:  Effect of antilymphocyte serum on animals experimentally infected with Histoplasma capsulatum or Cryptococcus neoformans . J Bacteriol 100:1271-1276, 1969;.
29 +
Grogan JB:  Survival of Pseudomonas aeruginosa in the peritoneal cavity of mice treated with antilymphocyte serum . Arch Surg 105:460-463, 1972;.
30 +
Bach MC, Sahyoun A, Adler JL, et al:  Influence of rejection therapy on fungal and nocardial infections in renal-transplant recipients . Lancet 1:180-184, 1973;.
31 +
Monaco AP, Lewis EJ, Latzina A, et al:  Clinical use of equine anti-human lymph node lymphocyte serum: Preliminary results in 21 mismatched cadaveric renal transplants , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 355-362.
32 +
Taylor HE:  Clinical trial of antilymphocyte serum , in Bach JF, Eyquem A (eds): International Symposium on Antilymphocyte Serum . Basel, Switzerland, S Karger, 1970;, vol 16, pp 343-348.
33 +
Epstein FH:  Nephrotic syndrome , in Wintrobe MM, Thorn GW, Adams RD, et al (eds): Harrison's Principles of Internal Medicine , ed 7. New York, McGraw-Hill Book Co Inc, 1974;, vol 2, p 1397.
34 +
Harlan WR Jr, Holden KR, Williams GM, et al:  Proteinuria and nephrotic syndrome associated with chronic rejection of kidney transplants . N Engl J Med 277:769-776, 1967;.
35 +
Hoyer JR, Raij L, Vernier RL, et al:  Recurrence of idiopathic nephrotic syndrome after renal transplantation . Lancet 2:343-348, 1972;.
36 +
Najarian JS, Foker JE:  Mechanisms of kidney allograft rejection . Transplant Proc 1:184-193, 1969;.
37 +
McCarthy LJ, Titus JL, Daugherty GW:  Bilateral renal-vein thrombosis and the nephrotic syndrome in adults . Ann Intern Med 58:837-857, 1963;.
38 +
Wilfert CM, Katz SL:  Etiology of bacterial sepsis in nephrotic children 1963-1967 . Pediatrics 42:840-843, 1968;.
39 +
Black JA, Challacombe DN, Ockenden BG:  Nephrotic syndrome associated with bacteremia after shunt operations for hydrocephalus . Lancet 2:921-924, 1965;.
40 +
Krebs RA, Burvant MU:  Nephrotic syndrome in association with varicella . JAMA 222:325-326, 1972;.

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