Cytomegalovirus (CMV) and Pneumocystis jirovecii fungus are the main opportunistic microorganisms that affect transplanted individuals. Immunosuppressive drugs administered to prevent organ rejection leave the immune system vulnerable to these infections. The present report is about a kidney transplanted patient using immunosuppressants who was diagnosed with cytomegalovirus and pneumocystosis requiring admission to the intensive care unit (ICU). Female patient, 57 years old, a kidney transplanted three years ago, with comorbidities, such as systemic arterial hypertension, hypertriglyceridemia and type 2 diabetes mellitus. She was admitted to the hospital in January 2020 with a history of diarrhea, cough, malaise and weight loss of seven kg in a month. She made continuous use of the immunosuppressants tacrolimus ® and mycophenolate sodium (MFS). After five days of hospitalization, she was transferred to the ICU due to refractory diarrhea, worsening renal function and respiratory pattern, requiring mechanical ventilation. Chest tomography showed changes that led to the diagnostic hypothesis of CMV pneumonia or Pneumocystis jirovecii . Treatment with Ganciclovir ® and Bactrim ® was started. The bronchial lavage polymerase chain reaction test confirmed the infectious condition for CMV and Pneumocystis jirovecii . Despite the drug therapy instituted, there was no improvement in the infectious condition. The patient started to present a general and progressive worsening of the clinical picture with loss of renal graft function, respiratory failure, metabolic acidosis, hemodynamic instability and severe distributive shock, evolving to death. In the present report, it was observed that after late kidney transplantation the fragility of the immune system caused by the use of immunosuppressants contributed to the development of a severe infection with CMV and Pneumocystis jirovecii . Adjusting the doses of immunosuppressants to individual needs can be an important measure for maintaining the proper immune system and consequently avoiding late opportunistic infections and death outcomes.
Pacheco, L., Manfro, R.C., Pestana, J.O.M., Neumann, J., Filho, M.A. and Garcia, V.D. (2019) Dimensionamento dos Transplantes no Brasil e em cada estado (2012-2019). Registro Brasileiro de Transplantes, 4 Edition, 88. http://www.abto.org.br/abtov03/Upload/file/RBT/2019/RBT-2019-leitura.pdf
Hertl, M. (2018)Visão geral dos transplantes-Imunologia. Manuais MSD edição para profissionais. https://www.msdmanuals.com/pt/profissional/imunologia-dist%C3%BArbios-al%C3%A9rgicos/transplante/vis%C3%A3o-geral-dos-transplantes
Tibiriçá, C.S.B., Augusto, V.T., Castilho, L.F., Dragosavac, D., Faez, D.C.S. and Passos, A.I.M. (2016) Caracterização de infecções pulmonares no pós-operatório tardio de transplante renal: Uma revisão integrativa. Rev Bras Em Promoção Saúde, 29, 107-116. https://periodicos.unifor.br/RBPS/article/view/4324
Souza, A.T.D. and Costa, J.R.D. (2013) A infecção por citomegalovírus em pacientes renais transplantados. Monografia [Trabalho de Conclusão de Curso apresentado como requisito parcial do curso de Bacharel em Enfermagem]-Faculdades Promove. http://nippromove.hospedagemdesites.ws/anais_simposio/arquivos_up/documentos/artigos/3c04d8d4781c6b88992104ecbcadec7c.pdf
Ribeiro, I.F. (2016) Infecção ativa pelo citomegalovírus, em pacientes transplantados renais, detectada pela PCR em tempo real. Tese-Universidade Federal do Ceará, 59-59. https://pesquisa.bvsalud.org/portal/resource/pt/biblio-972007
Fishman, J.A. (2020) Pneumocystis jiroveci. Seminars in Respiratory and Critical Care Medicine, 41, 141-157. https://doi.org/10.1055/s-0039-3399559
Nevez, G., Jounieaux, V., Linas, M.D., Guyot, K., Leophonte, P., Massip, P., et al. (1997) High Frequency of Pneumocystis carinii sp. f. hominis Colonization in HIV-Negative Patients. Journal of Eukaryotic Microbiology, 44, 36S. https://doi.org/10.1111/j.1550-7408.1997.tb05760.x
Breda, A. (2018) Kidney Transplantation: The Beauty and the Beast. European Urology Focus, 4, 139. https://doi.org/10.1016/j.euf.2018.07.026
Primc, D., Racki, S, Arnol M., Marinovic, M., Fucak-Primc, A., Muzur, A., et al. (2020) The Beginnings of Kidney Transplantation in South-East Europe. Acta clinica Croatica, 59, 135-140. https://doi.org/10.20471/acc.2020.59.01.16
Peeters, L.E.J., Andrews, L.M., Hesselink, D.A., de Winter, B.C.M. and van Gelder T. (2018) Personalized Immunosuppression in Elderly Renal Transplant Recipients. Pharmacological Research, 130, 303-307. https://doi.org/10.1016/j.phrs.2018.02.031
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Duran-Struuck, R., Sondermeijer, H.P., Bühler, L., Alonso-Guallart, P., Zitsman, J., Kato, Y., et al. (2017) Effect of Ex Vivo—Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques. Transplantation, 101, 274-283. https://doi.org/10.1097/TP.0000000000001559
Martin-Moreno, P.L., Tripathi, S. and Chandraker, A. (2018) Regulatory T Cells and Kidney Transplantation. Clinical Journal of the American Society of Nephrology, 13, 1760-1764. https://doi.org/10.2215/CJN.01750218
Mirzakhani, M., Shahbazi, M., Oliaei, F. and Mohammadnia-Afrouzi, M. (2019) Immunological Biomarkers of Tolerance in Human Kidney Transplantation: An Updated Literature Review. Journal of Cellular Physiology, 234, 5762-5774. https://doi.org/10.1002/jcp.27480
Scottà, C., Fanelli, G., Hoong, S.J., Romano, M., Lamperti, E.N., Sukthankar, M., et al. (2016) Impact of Immunosuppressive Drugs on the Therapeutic Efficacy of ex vivo Expanded Human Regulatory T cells. Haematologica,101, 91-100. https://haematologica.org/article/view/7611
Nash, A., Samoylova, M., Leuthner, T., Zhu, M., Lin, L., Meyer, J.N., et al. (2020) Effects of Immunosuppressive Medications on Mitochondrial Function. Journal of Surgical Research, 249, 50-57. https://doi.org/10.1016/j.jss.2019.12.010
Demirkiran, A., Sewgobind, V.D.K.D., van der Weijde, J., Kok, A., Baan, C.C., Kwekkeboom, J., et al. (2009) Conversion from Calcineurin Inhibitor to Mycophenolate Mofetil-Based Immunosuppression Changes the Frequency and Phenotype of CD4+FOXP3+ Regulatory T Cells. Transplantation, 87, 1062-1068. https://doi.org/10.1097/TP.0b013e31819d2032
He, X., Smeets, R.L., Koenen, H.J.P.M., Vink, P.M., Wagenaars, J., Boots, A.M.H., et al. (2011) Mycophenolic Acid-Mediated Suppression of Human CD4+ T Cells: More than Mere Guanine Nucleotide Deprivation. American Journal of Transplantation, 11, 439-449. https://doi.org/10.1111/j.1600-6143.2010.03413.x
Wu, T., Zhang, L., Xu, K., Sun, C., Lei, T., Peng, J., et al. (2012) Immunosuppressive Drugs on Inducing Ag-Specific CD4+CD25+Foxp3+ Treg Cells during Immune Response in Vivo. Transplant Immunology, 27, 30-38. https://doi.org/10.1016/j.trim.2012.05.001
Chen, X., Oppenheim, J.J., Winkler-Pickett, R.T., Ortaldo, J.R. and Howard, O.M.Z. (2006) Glucocorticoid Amplifies IL-2-Dependent Expansion of Functional FoxP3+ CD4+CD25+ T Regulatory Cells in Vivo and Enhances Their Capacity to Suppress EAE. European Journal of Immunology, 36, 2139-2149. https://doi.org/10.1002/eji.200635873
Webster, A.C., Lee, V.W.S., Chapman, J.R. and Craig, J.C. (2006) Target of Rapamycin Inhibitors (Sirolimus and Everolimus) for Primary Immunosuppression of Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Trials. Transplantation, 81, 1234-1248. https://doi.org/10.1097/01.tp.0000219703.39149.85
Malvezzi, P., Jouve, T. and Rostaing, L. (2016) Use of Everolimus-Based Immunosuppression to Decrease Cytomegalovirus Infection after Kidney Transplant. Experimental and Clinical Transplantation, 14, 361-366.
Jung, H-Y., Seo, M.Y., Jeon, Y., Huh, K.H., Park, J.B., Jung, C.W., et al. ( 2020) Tacrolimus Trough Levels Higher than 6ng/ml Might Not Be Required after a Year in Stable Kidney Transplant Recipients. PLoS ONE, 15, e0235418. https://doi.org/10.1371/journal.pone.0235418
Sagedal, S., Hartmann, A., Nordal, K.P., Osnes, K., Leivestad, T., Foss, A., et al. (2004) Impact of Early Cytomegalovirus Infection and Disease on Long-Term Recipient and Kidney Graft Survival. Kidney International, 66, 329-337. https://doi.org/10.1111/j.1523-1755.2004.00735.x
Arthurs, S.K., Eid, A.J., Pedersen, R.A., Kremers, W.K., Cosio, F.G., Patel, R., et al. (2008) Delayed-Onset Primary Cytomegalovirus Disease and the Risk of Allograft Failure and Mortality after Kidney Transplantation. Clinical Infectious Diseases, 46, 840-846. https://doi.org/10.1086/528718
Ramos, E., Drachenberg, C.B., Wali, R. and Hirsch, H.H. (2009) The Decade of Polyomavirus BK-Associated Nephropathy: State of Affairs. Transplantation, 87, 621-630. https://doi.org/10.1097/TP.0b013e318197c17d
Sellarés, J., Freitas, D.G. de, Mengel, M., Reeve, J., Einecke, G., Sis, B., et al. (2012) Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence. American Journal of Transplantation, 12, 388-399. https://doi.org/10.1111/j.1600-6143.2011.03840.x
Park, W.Y., Kang, S.S., Jin, K., Park, S.B., Choe, M. and Han. S. (2018) Long-Term Prognosis of BK Virus-Associated Nephropathy in Kidney Transplant Recipients. Kidney Research and Clinical Practice, 37, 167-173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027809/ https://doi.org/10.23876/j.krcp.2018.37.2.167
Da Costa, Y.R.F. (2009) A Transplantação Renal, O Pós-Transplante Imediato. Master Theses, Faculdade de Medicina da Universidade de Coimbra, 76. https://estudogeral.sib.uc.pt/handle/10316/27553
Chen, S-J., Wang, S-C. and Chen, Y-C. (2020) Antiviral Agents as Therapeutic Strategies against Cytomegalovirus Infections. Viruses, 12, Article No. 21. https://doi.org/10.3390/v12010021
Bhagwat, S.P., Gigliotti, F., Wang, J., Wang, Z., Notter, R.H., Murphy, P.S., et al. (2018) Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity against Pneumocystis Infection. Frontiers in Immunology, 9, Article No. 2131. https://doi.org/10.3389/fimmu.2018.02131
Lufft, V., Kliem, V., Behrend, M., Pichlmayr, R., Koch, K.M. and Brunkhorst, R. (1996) Incidence of Pneumocystis carinii Pneumonia after Renal Transplantation: Impact of Immunosuppression. Transplantation, 62, 421-423. https://doi.org/10.1097/00007890-199608150-00022
Hardy, A.M., Wajszczuk. C.P., Suffredini, A.F., Hakala, T.R. and Ho, M. (1984) Pneumocystis carinii Pneumonia in Renal-Transplant Recipients Treated with Cyclosporine and Steroids. Journal of Infectious Diseases, 149, 143-147. https://doi.org/10.1093/infdis/149.2.143
Roman, R. and Traesel. M.A. (2006) Distúrbios hidroeletrolíticos na prática clínica diária. Acta Méd Porto Alegre, 1, 389-397.
Gusmão, F. (2008) Hipernatremia. MedicinaNET. http://www.medicinanet.com.br/conteudos/revisoes/1344/hipernatremia.htm
Sodré, F.L., Costa, J.C.B. and Lima, J.C.C. (2007) Evaluation of Renal Function and Damage: A Laboratorial Challenge. Jornal Brasileiro de Patologia e Medicina Laboratorial, 43, 329-337. https://doi.org/10.1590/S1676-24442007000500005
Teixeira, L. (2013) Indicadores bioquímicos da função renal. Seminário apresentado na disciplina Bioquímica do tecido animal, no Programa de Pós-Graduação em Ciências Veterinárias da Universidade Federal do Rio Grande do Sul. https://www.ufrgs.br/lacvet/site/wp-content/uploads/2013/10/renalLiege.pdf
Revanur, V.K., Jardine, A.G., Kingsmore, D.B., Jaques, B.C., Hamilton, D.H. and Jindal, R.M. (2001) Influence of Diabetes Mellitus on Patient and Graft Survival in Recipients of Kidney Transplantation. Clinical Transplantation, 15, 89-94. https://onlinelibrary.wiley.com/doi/epdf/10.1034/j.1399-0012.2001.150202.x https://doi.org/10.1034/j.1399-0012.2001.150202.x
Cosio, F.G., Pesavento, T.E., Kim, S., Osei, K., Henry, M. and Ferguson, R.M. (2002) Patient Survival after Renal Transplantation: IV. Impact of Post-Transplant Diabetes. Kidney International, 62, 1440-1446. https://doi.org/10.1111/j.1523-1755.2002.kid582.x
Carpenter, M.A., Weir, M.R., Adey, D.B., House, A.A., Bostom, A.G. and Kusek, J.W. (2012) Inadequacy of Cardiovascular Risk Factor Management in Chronic Kidney Transplantation—Evidence from the FAVORIT Study. Clinical Transplantation, 26, E438-E446. https://doi.org/10.1111/j.1399-0012.2012.01676.x
Weinrauch, L.A., D’Elia, J.A., Weir, M.R., Bunnapradist, S., Finn, P.V., Liu, J., et al. (2018) Infection and Malignancy Ou.egh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial. The American Journal of Medicine, 131, 165-172. https://doi.org/10.1016/j.amjmed.2017.08.038
Opelz, G., Wujciak, T. and Ritz, E. (1998) Association of Chronic Kidney Graft Failure with Recipient Blood Pressure. Kidney International, 53, 217-222. https://doi.org/10.1046/j.1523-1755.1998.00744.x
Weir, M.R. (2004) Blood Pressure Management in the Kidney Transplant Recipient. Advances in Chronic Kidney Disease, 11, 172-183. https://doi.org/10.1053/j.arrt.2004.01.004