Infecções virais no rim transplantado

Transcrição

1 Infecções virais no rim transplantado Gabriel Teixeira Montezuma Sales Nefrologista Pós graduando em Nefrite

2 INTRODUÇÃO Neoplasia DAE Perda do enxerto Infecção Viral Rejeição Mortalidade Cukuranovic et al. Viral Infection in Renal Transplatation. The Sci W Journal.2012.

3 INTRODUÇÃO Virúria x viremia x doença BK Vírus > Adenovírus >>> CMV / HSV Cukuranovic et al. Viral Infection in Renal Transplatation. The Sci W Journal.2012.

4 POLIOMAVÍRUS Família Polyomaviridae JC virus e Simian Virus 40 Sorologia positiva em ~50-80% dos adultos Assintomáticos Forma de transmissão Vigil et al. BK nephropathy in native kidneys. World J Transplant 2016; 24; 6(3)

5 POLIOMAVÍRUS EPIDEMIOLOGIA Sawinski et al. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant (2015) 30:

6 POLIOMAVÍRUS PATOGÊNESE BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches. Lamarche et al. Transplantation 2016; 100:

7 POLIOMAVÍRUS PATOGÊNESE BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches. Lamarche et al. Transplantation 2016; 100:

8 POLIOMAVÍRUS VIA DE TRANSMISSÃO D+ 23%, R 14% Schwarz et al. Viral origin, clinical course and renal outcomes in patients with BK virus infection after living-donor renal transplantation. Transplantation 2016; 100:

9 POLIOMAVÍRUS MANIFESTAÇÕES CLÍNICAS Assintomático Perda progressiva da função renal U1 inespecífica Estenose ureteral Cistite hemorrágica Neoplasias (??) Sharma et al. BK virus in kidney transplant: current concepts, recent advances, and future directions. Exp and Clin Transplantation (2016) 4: Journal of the American Society of Nephrology

10 POLIOMAVÍRUS DIAGNÓSTICO Decoy cells PCR em urina e sérico Diversas proteínas possíveis (VP1) Imunohistoquímica = SV 40 Hibridização in situ Sawinski et al. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant (2015) 30:

11 POLIOMAVÍRUS DIAGNÓSTICO Sharma et al. BK virus in kidney transplant: current concepts, recent advances, and future directions. Exp and Clin Transplantation (2016) 4: Journal of the American Society of Nephrology

12 POLIOMAVÍRUS DIAGNÓSTICO Sawinski et al. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant (2015) 30:

13 POLIOMAVÍRUS TRATAMENTO Redução de Imunossupressão!!!

14 POLIOMAVÍRUS TRATAMENTO Sawinski et al. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant (2015) 30:

15 POLIOMAVÍRUS TRATAMENTO Lamarche et al. BK Polyomavirus and the Transplanted Kidney: Immunopathology and Therapeutic Approaches. Transplantation 2016; 100:

16 POLIOMAVÍRUS TRATAMENTO

17 POLIOMAVÍRUS TRATAMENTO Doesum et al. Incidence and outcome of BK Polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine, mycophenolate, or everolimus-based low dose imunossupressive therapy. Transpl Infect Dis 2017, Jun; 19(3)

18 POLIOMAVÍRUS TRATAMENTO Jamboti JS. BK virus nephropathy in renal transplant recipientes. Nephrology. 21 (2016)

19 POLIOMAVÍRUS TRATAMENTO Jamboti JS. BK virus nephropathy in renal transplant recipientes. Nephrology. 21 (2016)

20 POLIOMAVÍRUS TRATAMENTO KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipient. Am J of Transplantation. 2009; 9 (Suppl 3): S44 S58

21 POLIOMAVÍRUS SCREENING KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipient. Am J of Transplantation. 2009; 9 (Suppl 3): S44 S58

22 POLIOMAVÍRUS PROGNÓSTICO Nickeleit et al. The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations. J Am Soc Nephrol 29: ccc ccc, 2017

23 POLIOMAVÍRUS X REJEIÇÃO

24 POLIOMAVÍRUS X REJEIÇÃO Sigdel et al. Intragraft Antiviral-specific gene expression as a distinctive transcriptional signature for studies in polyomavirus-associated nephropathy. Transplantation 2016; 100:

25 POLIOMAVÍRUS X REJEIÇÃO 61% de Rejeição, 15% de perda 22% de perda por BKVAN exclusiva Nankivell et al. BK Virus nephropathy: histological evolution by sequential pathology. Am J Transplantation 2017; 17:

26 ADENOVÍRUS Família Adenoviridae A a F 7, 21, 34, 35 e 37 Tropismo por TGI e vias aéreas Crianças e surtos IgG+ em ~95% dos adultos Gompf SG. Adenovirus. Medscape May 2017

27 ADENOVÍRUS TX - EPIDEMIOLOGIA Incidência ± 5% Transmissão De novo x reativação x enxerto Fatores de risco Imunossupressão < 1 ano pós-tx Status sorológico? Florescu et al. What do we know about adenovirus in renal transplatation. Nephrol Dial Transplant 28: , 2013c

28 ADENOVÍRUS APRESENTAÇÃO CLÍNICA Oligossintomático Cistite hemorrágica e pneumonia Doença disseminada Florescu et al. What do we know about adenovirus in renal transplatation. Nephrol Dial Transplant 28: , 2013c

29 ADENOVÍRUS MANIFESTAÇÕES RENAIS Kolankiewickz et al. Adenvirus nephropathy and obstructive uropathy in a renal transplant recipient: case report and literature review. NDT plus (2010) 10:

30 ADENOVÍRUS CISTITE

31 ADENOVÍRUS TX - NEFRITE Watcharanana et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplantation 2011; 11:

32 Nannoku et al. HAdV infection after renal transplantation. Transp Infect Dis 2016: 18: ADENOVÍRUS DIAGNÓSTICO Cultura de urina Até 28 dias Antígeno urinário / Vírion PCR urinário e sérico Histopatologia Hibridização in situ imunohistoquímica

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36 ADENOVÍRUS TRATAMENTO MPS e FK ISS ISS MPS Nannoku et al. HAdV infection after renal transplantation. Transp Infect Dis 2016: 18:

37 ADENOVÍRUS TRATAMENTO 2 Semanas Cidofovir 1mg/kg 3x/semana Cidofovir 5mg/kg 1x/semana Até melhora dos sintomas Cidofovir 5mg/Kg 1x/2 semanas 3 exames negativos Suspensão de tratamento > 1 semana de intervalo TFG < 50mL/min => 50% da dose. Se TRS, fazer longe de HD Watcharanana et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplantation 2011; 11:

38 ADENOVÍRUS TRATAMENTO - CIDOFOVIR Fazer se quadro grave / risco de vida Doença disseminada / hepatite / pneumonia Efeitos colaterais 50% nefrotoxicidade grave Neutropenia Uveíte Probenecide? Watcharanana et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplantation 2011; 11:

39 ADENOVÍRUS TRATAMENTO - OUTROS Ribavirina Efetiva contra poucos sorotipos Imunoglobulina Hipogamaglobulinemia Casos graves Hatlen et al. Disseminated adenovirus Nephritis after Kidney Transplanttion. Kidney int rep (2018) 3, 19-23

40 ADENOVÍRUS TRATAMENTO Prasad et al. Treatment of Adenovirus (AdV) Infection in Allogeneic Hematopoietic Cell Transplant (allo HCT) Patients (pts) with Brincidofovir: Final 36 Week Results from the Advise Trial Biol Blood Marrow Transplant 23 (2017) S18 S391

41 ADENOVÍRUS SEGUIMENTO Seguir com mesmo método do diagnóstico PCR semanal? 2 semanas > viremia negativa 4,5 semanas > virúria negativa Watcharanana et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplantation 2011; 11:

42 ADENOVÍRUS PROGNÓSTICO Doença localizada Excelente prognóstico Doença disseminada Mortalidade 18-60% Risco de Rejeição Watcharanana et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplantation 2011; 11:

43 CITOMEGALOVÍRUS Família Herpesvírus Herpes 5 95% dos adultos IgG+ Transmissão por qualquer fluido humano Kotton et al. The third international consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation ahead of print, 2018.

44 CITOMEGALOVÍRUS EPIDEMIOLOGIA 40 a 100% dos Tx Infecção Até 60% doença Fatores de risco Imunossupressão mtor x Micofenolato Status sorológico Bx por DAE, 1% com CMV em IF Kotton et al. The third international consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation ahead of print, 2018.

45 CITOMEGALOVÍRUS DIAGNÓSTICO Infecção => antigenemia / PCR Doença Síndrome CMV Lesão de órgao alvo (imunohistoquimica) Nefrite DAE + hematúria, com ou sem sintomas de cistite Vichot et al. Cytomegalovirus glomerulopathy and cytomegalovirus interstitial nephritis on sequential transplant kidney biopsies. Am J Kidney Dis. 2014; 63 (3):

46 CITOMEGALOVÍRUS DIAGNÓSTICO Chikeka et al. Concurrent cytomegalovirus glomerulitis and BK polyomavirus-associated nepbropathy in a kidney allograft biopsy. Transpl Infect dis 2016; 18:

47 CITOMEGALOVÍRUS DIAGNÓSTICO Chikeka et al. Concurrent cytomegalovirus glomerulitis and BK polyomavirus-associated nepbropathy in a kidney allograft biopsy. Transpl Infect dis 2016; 18:

48 CITOMEGALOVÍRUS TRATAMENTO Kotton et al. The third international consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation ahead of print, 2018.

49 CITOMEGALOVÍRUS PROFILAXIA Kotton et al. The third international consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation ahead of print, 2018.

50 HERPES SIMPLES Hemmersbach-Miller et al. Hemorrhagic Herpes Simplex Virus Type 1 Nephritis: an Unusual Cause of Acute Allograft Dysfunction. Am J Transplantation 2017; 17:

51 INFECÇÕES VIRAIS mtor Bowman et al. The Role of mtor Inhibitors in the Management of Viral Infections: A Review of Current Literature. Transplantation 2018; 102: S50-S59.

52 OBRIGADO