Tuberculosis in renal transplant patients

Paula, Flávio Jota de; Azevedo, Luiz Sérgio; Saldanha, Luiz Balthazar; Ianhez, Luiz Estevam; Sabbaga, Emil

doi:10.1590/S0036-46651987000500002

Abstracts

Tuberculosis (TB) was diagnosed in 25 of 466 patients who underwent renal transplant over a period of 15 years. TB developed from 1 month to 9 years post-transplant. In 56% of the cases the onset was within the first post-transplant year. TB affected several isolated or combined organs. Pulmonary involvement was present in 76% of cases, either as isolated pleuro-pulmonary (56%) or associated with other sites (20%). The non-pulmonary sites were: skin, joints, tests, urinary tract, central nervous system and lymphonodules. The diagnosis was confirmed by biopsy in 64% of the cases, by identification of tubercle bacilli in 24% and only at necropsy in 12% Biopsy specimens could be classified in three histological forms: exudative, that occurred in early onset and more severe cases granulomatous in late onset and benign cases; and mixed in intermediate cases. Azathioprine dosages were similar along post-transplant time periods in TB patients and in the control groups; and in TB patients who were cured and who died. The number of steroid treated rejection crises was greater in TB than in the control group. Prednisone doses were higher and the number of rejection crises was greater in TB patients who died than in those who were cured. Fifteen patients were cured and ten died, two of them of causes unrelated to TB. Six of the eight TB-related deaths occurred in the first 6 post-transplant months. The outcome was poor in patients in whom TB arose early in post-transplant period and where the exudative or mixed forms were present; whereas the prognosis was good in patients with late onset and granulomatous form of TB. In one patient TB was transmitted by the allograft.

Tuberculosis; Kidney transplantation; Infection; Immunosuppression

Tuberculose (TB) foi diagnosticada em 25 de 466 pacientes submetidos a transplante renal. A TB surgiu entre 1 mês e 9 anos pós-transplante. O pulmão foi acometido em 76% dos casos, isoladamente (56%), ou associado a outras localizações (20%). Os outros órgãos envolvidos foram: pele, articulações, testículos, trato urinário, sistema nervoso central e linfonodos. O diagnóstico foi confirmado por biópsia em 64% dos casos, pela identificação do bacilo em 24% e apenas à necrópsia em 12%. Três formas histológicas foram identificadas: exudativa (nos casos de aparecimento precoce e de maior gravidade) granulomatosa (naqueles benignos e de aparecimento tardio) e mista (naqueles intermediários). As doses de azatioprina foram constantes ao longo do período pós-transplante, tanto no grupo tuberculoso como no controle, bem como nos pacientes tuberculosos que faleceram e que se curaram. O número de crises de rejeição tratadas foi maior no grupo TB do que no grupo controle. As doses de prednisona e o número de crises de rejeição foram maiores nos pacientes tuberculosos que faleceram do que naqueles que sobreviveram. Quinze pacientes se curaram e 10 faleceram, oito de causas relacionadas à TB, Seis destes óbitos ocorreram nos 6 primeiros meses pós-transplante. Em um paciente a TB foi transmitida pelo enxerto.

ORIGINAL ARTICLES

Tuberculosis in renal transplant patients

Tuberculose em pacientes transplantados renais

Flávio Jota de Paula; Luiz Sérgio Azevedo; Luiz Balthazar Saldanha; Luiz Estevam Ianhez; Emil Sabbaga

Renal Transplant Unit. "Hospital das Clínicas" of University of São Paulo Medical School

^{Address for correspondence} Address for correspondence: Dr. Flávio Jota de Paula Unidade de Transplante Renal Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Av. Dr. Enéas de Carvalho Aguiar, 255 Caixa Postal 8091. CEP 05403 São São Paulo, SP - Brasil

SUMMARY

Tuberculosis (TB) was diagnosed in 25 of 466 patients who underwent renal transplant over a period of 15 years. TB developed from 1 month to 9 years post-transplant. In 56% of the cases the onset was within the first post-transplant year. TB affected several isolated or combined organs. Pulmonary involvement was present in 76% of cases, either as isolated pleuro-pulmonary (56%) or associated with other sites (20%). The non-pulmonary sites were: skin, joints, tests, urinary tract, central nervous system and lymphonodules. The diagnosis was confirmed by biopsy in 64% of the cases, by identification of tubercle bacilli in 24% and only at necropsy in 12% Biopsy specimens could be classified in three histological forms: exudative, that occurred in early onset and more severe cases granulomatous in late onset and benign cases; and mixed in intermediate cases. Azathioprine dosages were similar along post-transplant time periods in TB patients and in the control groups; and in TB patients who were cured and who died. The number of steroid treated rejection crises was greater in TB than in the control group. Prednisone doses were higher and the number of rejection crises was greater in TB patients who died than in those who were cured. Fifteen patients were cured and ten died, two of them of causes unrelated to TB. Six of the eight TB-related deaths occurred in the first 6 post-transplant months. The outcome was poor in patients in whom TB arose early in post-transplant period and where the exudative or mixed forms were present; whereas the prognosis was good in patients with late onset and granulomatous form of TB. In one patient TB was transmitted by the allograft.

Key words: Tuberculosis; Kidney transplantation; Infection; Immunosuppression.

RESUMO

Tuberculose (TB) foi diagnosticada em 25 de 466 pacientes submetidos a transplante renal. A TB surgiu entre 1 mês e 9 anos pós-transplante. O pulmão foi acometido em 76% dos casos, isoladamente (56%), ou associado a outras localizações (20%). Os outros órgãos envolvidos foram: pele, articulações, testículos, trato urinário, sistema nervoso central e linfonodos. O diagnóstico foi confirmado por biópsia em 64% dos casos, pela identificação do bacilo em 24% e apenas à necrópsia em 12%. Três formas histológicas foram identificadas: exudativa (nos casos de aparecimento precoce e de maior gravidade) granulomatosa (naqueles benignos e de aparecimento tardio) e mista (naqueles intermediários). As doses de azatioprina foram constantes ao longo do período pós-transplante, tanto no grupo tuberculoso como no controle, bem como nos pacientes tuberculosos que faleceram e que se curaram. O número de crises de rejeição tratadas foi maior no grupo TB do que no grupo controle. As doses de prednisona e o número de crises de rejeição foram maiores nos pacientes tuberculosos que faleceram do que naqueles que sobreviveram. Quinze pacientes se curaram e 10 faleceram, oito de causas relacionadas à TB, Seis destes óbitos ocorreram nos 6 primeiros meses pós-transplante. Em um paciente a TB foi transmitida pelo enxerto.

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Recebido para publicação em 07/2/1986.

1. ALLEN, R. D. M.; HUNNISETT, A. G. & MORRIS, P. J. - Cyclosporin and rifampicin in renal transplantation. Lancet, 1: 1342-1343, 1985.
2 ANDREW, O. T.; SCHOENFELD, P. Y.; HOPWELL, P. C. & HUMPHREYS, M. H. - Tuberculosis in patients with end-stage renal disease. Amer. J. Med., 68: 59-65, 1980.
3. ASCHER, N. L.; SIMMONS, R. L.; MARKER, S.; KLUGMAN, J. & NAJARIAN, J. S. - Tuberculosis joint disease in transplant patients. Amer. J. Surg., 135: 853-856, 1978.
4. BATATA, M. A. - Pulmonary tuberculosis in a renal transplant recipient. J. Amer. med. Ass., 237: 1465, 1977.
5. BELL, T. J. & WILLIAMS, G. B. - Successful treatment of tuberculosis in renal transplant recipients. J. roy. Soc. Med., 71: 265-268, 1978.
6. BRÓLIO, R. & LIMA FILHO, M. T. - Tuberculose pulmonar. In: VERONESI, R., ed. - Doenças infecciosas e parasitárias. 6Ş ed. Rio de Janeiro, Guanabara Koogan, 1976. p. 317-338.
7. CASSIDY, M. J. D.; ZYL-SMIT, R. V.; PASCOE, M. D.; SWANEPOEL, C R. & JACOBSON, J. E. - Effect of rifampicin on cyclosporin-A blood levels in a renal transplant recipients. Nephron, 41: 207, 1985.
8. COUTTS, I. I.; JEGARAJAH, S. & STARK, J. E. - Tuberculosis in renal transplant recipients. Brit J. Dis. Chest, 73: 141, 1979.
9. COWARD, R. A.; RAFTERY, A. T. & BROWN, C B. - Cyclosporin and anti-tuberculous therapy. Lancet, 1: 1342-1343, 1985.
10. DOBBELSTEIN, H. - Immune system in uremia. Nephron, 17: 409-412, 1976.
11. EDWARDS, O. M.; EVANS, R. J. C; GALLEY, J. M.; HUNTER, J. & TAIT, A. D. - Changes in Cortisol metabolism following rifampicin therapy. Lancet, 2: 549-551, 1974.
12. FORSLUND, T.; LAASONEN, L.; HÖCKERSTEDT, K.; STENMAN, S. & EDGREN, J. - Tuberculosis of the colon in a Ifcidney transplant patient. Acta. Med. Scand., 215: 181-184, 1984.
13. LAKSHMINARAYAN, S. & SAHN, S. A. - Tuberculosis in a patient after renal transplantation. Tubercle, 54: 72-76, 1973.
14. LANGHOFF, E. & MADSEN, S. - Rapid metabolism of cyclosporin and prednisone in kidney transplant patient receiving tuberculostatic treatment. Lancet, 2: 1031, 1983.
15. LICHTENSTEIN, I. H. & MacGREGOR, R. R. - Mycobacterial infections in renal transplant recipients: report of five cases and review of the literature. Rev. infect. Dis., 5: 216, 1983.
16. LLOVERAS, J.; PETERSON, P. K; SIMMONS, R. L. & NAJARIAN, J. S. - Mycobacterial infections in renal transplant recipients. Arch. intern. Med., 142: 888-892, 1983.
17. McALLISTER, W. A. C; THOMPSON, P. J.; AL-HABET, S. M. & ROGERS, H. J. - Rifampicin reduces effectiveness and bioavailability of predmisolene. Brit. med. J., 286: 923-925, 1983.
18. McWHINNEY, N.; KHAN, O. & WILLIAMS, G. - Tuberculosis in patients undergoing maintenance haemodialysis and renal transplantation. Brit. J. Surg., 68: 408-411, 1981.
19. MILLAR, J. W. & HORNE, N. W. - Tuberculosis in immunosuppressed patients. Lancet, 1: 1176-1178, 1979.
20. MORRIS, P. J. ed. - Kidney transplantation. Principles and practice. London, Grune & Stratton, 1984. p. 239-279, 427-467.
21. MOURAD, G.; SOULILLOU, J. D.; CHONG, G.; POULIQUEN, M. & HOURMANT, M. - Transmission of Mycobacterium tuberculosis with renal allografts. Nephron, 41: 82-86, 1985.
22. NEFF, T. A. & HUDGEL, D. W. - Miliary tuberculosis in a renal transplant recipient. Amer. Rev. resp. Dis., 108: 677-678, 1973.
23. OFFERMANN, G.; KELLER, F. & MOLZAHN, M. - Low cyclosporin-A blood levels and acute graft rejection in a renal transplant recipient during rifampicin treatment. Amer. J. Nephrol., 5: 385-387, 1985.
24. ORTUNO, J.; TERUEL, J. L. & MARCEN, R. - Primary intestinal tuberculosis following renal transplantation. Nephron, 31: 59-62, 1982.
25. PETERS, T. G.; REITER, C. G. & BOSWELL, R. L. - Transmission of tuberculosis by kidney transplantation. Transplantation, 38: 514-516, 1984.
26. RATTAZZI, L. C; SIMMONS, R. L.; SPANOS, P. K.; BRADFORD, D. S. & NAJARIAN, J. S. - Successful management of miliary tuberculosis. Amer. J. Surg., 130: 359-361, 1975.
27. REVILLARD, J. P. - Immunological alterations in chronic renal insufficiency. Advanc. Nephrol., 8: 365-370, 1979.
28. RIFKIND, D.; MARCHIORO, T. L.; WADDELL, W. R. & STARZL, T. E. - Infectious diseases associated with renal homotransplantation. J. Amer. med. Ass., 189: 397-407, 1964.
29. SAHN, S. A. & LAKSHMINARAYAN, S. - Tuberculosis after corticosteroid therapy. Brit. J. Dis. Chest, 70: 195-198, 1976.
30. THOMAS, P. A.; MOZES, M. F. & JONASSON, O. - Hepatic dysfunction during isoniazid chemoprophylaxis in renal allograft recipients. Arch. Surg., 114: 597-599, 1979.
31. TUBERCULOSIS in renal transplant patients. Editorial Tubercle, 60: 193-194, 1979.

Address for correspondence:

Dr. Flávio Jota de Paula

Unidade de Transplante Renal

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Av. Dr. Enéas de Carvalho Aguiar, 255

Caixa Postal 8091. CEP 05403 São São Paulo, SP - Brasil

Publication Dates

Publication in this collection
17 Feb 2011
Date of issue
Oct 1987

History

Received
07 Feb 1986

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALLEN, R. D. M.; HUNNISETT, A. G. & MORRIS, P. J. - Cyclosporin and rifampicin in renal transplantation. Lancet, 1: 1342-1343, 1985.

[2] 2 ANDREW, O. T.; SCHOENFELD, P. Y.; HOPWELL, P. C. & HUMPHREYS, M. H. - Tuberculosis in patients with end-stage renal disease. Amer. J. Med., 68: 59-65, 1980.

[3] 3. ASCHER, N. L.; SIMMONS, R. L.; MARKER, S.; KLUGMAN, J. & NAJARIAN, J. S. - Tuberculosis joint disease in transplant patients. Amer. J. Surg., 135: 853-856, 1978.

[4] 4. BATATA, M. A. - Pulmonary tuberculosis in a renal transplant recipient. J. Amer. med. Ass., 237: 1465, 1977.

[5] 5. BELL, T. J. & WILLIAMS, G. B. - Successful treatment of tuberculosis in renal transplant recipients. J. roy. Soc. Med., 71: 265-268, 1978.

[6] 6. BRÓLIO, R. & LIMA FILHO, M. T. - Tuberculose pulmonar. In: VERONESI, R., ed. - Doenças infecciosas e parasitárias. 6Ş ed. Rio de Janeiro, Guanabara Koogan, 1976. p. 317-338.

[7] 7. CASSIDY, M. J. D.; ZYL-SMIT, R. V.; PASCOE, M. D.; SWANEPOEL, C R. & JACOBSON, J. E. - Effect of rifampicin on cyclosporin-A blood levels in a renal transplant recipients. Nephron, 41: 207, 1985.

[8] 8. COUTTS, I. I.; JEGARAJAH, S. & STARK, J. E. - Tuberculosis in renal transplant recipients. Brit J. Dis. Chest, 73: 141, 1979.

[9] 9. COWARD, R. A.; RAFTERY, A. T. & BROWN, C B. - Cyclosporin and anti-tuberculous therapy. Lancet, 1: 1342-1343, 1985.

[10] 10. DOBBELSTEIN, H. - Immune system in uremia. Nephron, 17: 409-412, 1976.

[11] 11. EDWARDS, O. M.; EVANS, R. J. C; GALLEY, J. M.; HUNTER, J. & TAIT, A. D. - Changes in Cortisol metabolism following rifampicin therapy. Lancet, 2: 549-551, 1974.

[12] 12. FORSLUND, T.; LAASONEN, L.; HÖCKERSTEDT, K.; STENMAN, S. & EDGREN, J. - Tuberculosis of the colon in a Ifcidney transplant patient. Acta. Med. Scand., 215: 181-184, 1984.

[13] 13. LAKSHMINARAYAN, S. & SAHN, S. A. - Tuberculosis in a patient after renal transplantation. Tubercle, 54: 72-76, 1973.

[14] 14. LANGHOFF, E. & MADSEN, S. - Rapid metabolism of cyclosporin and prednisone in kidney transplant patient receiving tuberculostatic treatment. Lancet, 2: 1031, 1983.

[15] 15. LICHTENSTEIN, I. H. & MacGREGOR, R. R. - Mycobacterial infections in renal transplant recipients: report of five cases and review of the literature. Rev. infect. Dis., 5: 216, 1983.

[16] 16. LLOVERAS, J.; PETERSON, P. K; SIMMONS, R. L. & NAJARIAN, J. S. - Mycobacterial infections in renal transplant recipients. Arch. intern. Med., 142: 888-892, 1983.

[17] 17. McALLISTER, W. A. C; THOMPSON, P. J.; AL-HABET, S. M. & ROGERS, H. J. - Rifampicin reduces effectiveness and bioavailability of predmisolene. Brit. med. J., 286: 923-925, 1983.

[18] 18. McWHINNEY, N.; KHAN, O. & WILLIAMS, G. - Tuberculosis in patients undergoing maintenance haemodialysis and renal transplantation. Brit. J. Surg., 68: 408-411, 1981.

[19] 19. MILLAR, J. W. & HORNE, N. W. - Tuberculosis in immunosuppressed patients. Lancet, 1: 1176-1178, 1979.

[20] 20. MORRIS, P. J. ed. - Kidney transplantation. Principles and practice. London, Grune & Stratton, 1984. p. 239-279, 427-467.

[21] 21. MOURAD, G.; SOULILLOU, J. D.; CHONG, G.; POULIQUEN, M. & HOURMANT, M. - Transmission of Mycobacterium tuberculosis with renal allografts. Nephron, 41: 82-86, 1985.

[22] 22. NEFF, T. A. & HUDGEL, D. W. - Miliary tuberculosis in a renal transplant recipient. Amer. Rev. resp. Dis., 108: 677-678, 1973.

[23] 23. OFFERMANN, G.; KELLER, F. & MOLZAHN, M. - Low cyclosporin-A blood levels and acute graft rejection in a renal transplant recipient during rifampicin treatment. Amer. J. Nephrol., 5: 385-387, 1985.

[24] 24. ORTUNO, J.; TERUEL, J. L. & MARCEN, R. - Primary intestinal tuberculosis following renal transplantation. Nephron, 31: 59-62, 1982.

[25] 25. PETERS, T. G.; REITER, C. G. & BOSWELL, R. L. - Transmission of tuberculosis by kidney transplantation. Transplantation, 38: 514-516, 1984.

[26] 26. RATTAZZI, L. C; SIMMONS, R. L.; SPANOS, P. K.; BRADFORD, D. S. & NAJARIAN, J. S. - Successful management of miliary tuberculosis. Amer. J. Surg., 130: 359-361, 1975.

[27] 27. REVILLARD, J. P. - Immunological alterations in chronic renal insufficiency. Advanc. Nephrol., 8: 365-370, 1979.

[28] 28. RIFKIND, D.; MARCHIORO, T. L.; WADDELL, W. R. & STARZL, T. E. - Infectious diseases associated with renal homotransplantation. J. Amer. med. Ass., 189: 397-407, 1964.

[29] 29. SAHN, S. A. & LAKSHMINARAYAN, S. - Tuberculosis after corticosteroid therapy. Brit. J. Dis. Chest, 70: 195-198, 1976.

[30] 30. THOMAS, P. A.; MOZES, M. F. & JONASSON, O. - Hepatic dysfunction during isoniazid chemoprophylaxis in renal allograft recipients. Arch. Surg., 114: 597-599, 1979.

[31] 31. TUBERCULOSIS in renal transplant patients. Editorial Tubercle, 60: 193-194, 1979.