Mini topic 신장내과 R3 오동준 신장이식 후 감염병 Infectious Disease in Kidney-Transplant Recipients

II. 이식 후 감염병의 접근

Prevalence of transplantation in Korea 질병관리본부, 2011 장기이식통계연보 국립장기이식관리센터 (KONOS) 연 도연 도총계 고형장기 소계신장간장췌장심장폐 2000(2. 9~) 1, ,776 1, ,739 1, ,876 1, ,072 1, ,083 1, ,344 1, ,362 1, ,858 2,211 1, ,170 2,353 1,237 1, ,135 2,472 1,287 1, ,798 3,030 1,639 1, ,845 3,191 1,763 1,

Survival rate of recipients by organ type 질병관리본부, 2011 장기이식통계연보

Causes of death with function 2012 USRDS(U.S renal data system) annual data report

I. 서론 III. 신장 이식 후 시기별 감염병 IV. 우리나라에서 중요한 기회감염병 V. 결론 Cytomegalovirus 11 Pneumocystis jirovecii 22 Tuberculosis 33 II. 이식 후 감염병의 접근

Risk evaluation of infection Epidemiologic exposure Net state of immunosuppr ession Risk of infection Donor-derived infection Recipient- derived infection Nosocomial infection Community acquired infection

Risk evaluation of infection Epidemiologic exposure Net state of immunosuppr ession Risk of infection Immunosuppressive therapy: type, dose, duration Integrity of the mucocutaneous barrier: catheters, epithelial surfaces Neutropenia, lymphopenia Metabolic conditions Uremia, malnutrition, diabetes. Alcoholism with cirrhosis Infection with immunomodulating viruses CMV, EB virus, HBV, HCV, HIV Immunosuppressive therapy: type, dose, duration Integrity of the mucocutaneous barrier: catheters, epithelial surfaces Neutropenia, lymphopenia Metabolic conditions Uremia, malnutrition, diabetes. Alcoholism with cirrhosis Infection with immunomodulating viruses CMV, EB virus, HBV, HCV, HIV

I. 서론 III. 신장 이식 후 시기별 감염병 IV. 우리나라에서 중요한 기회감염병 V. 결론 Cytomegalovirus 11 Pneumocystis jirovecii 22 Tuberculosis 33 II. 이식 후 감염병의 접근

Timeline of Infection after Organ TPL Fishman JA, NEJM 2007

I. 서론 III. 신장 이식 후 시기별 감염병 IV. 우리나라에서 중요한 기회감염병 V. 결론 Cytomegalovirus 11 Pneumocystis jirovecii 22 Tuberculosis 33 II. 이식 후 감염병의 접근

Epidemiology Most commonly recognized viral pathogen –Incidence of CMV in the renal TPL 8-32% (USA), 54-61% (Korea) Symptomatic CMV infection: 5% (- 24.6%) (Korea) –High seropositivity in general population % (adult) in Korea  Reactivation of latent virus >> primary infection Risk factor of symptomatic CMV infection In case of D+/R - > D+/R+, D-/R+ Increased immunosuppressive exposure (ex. Cytolytic agent ;OKT3) Presence of rejection

Onset of CMV infection Blair C et al, Clin J Am Soc Nephrol, 2008.

Cytomegalovirus Infection Fishman JA. NEJM 2007;357:

Cytomegalovirus Infection – Indirect effects Fishman JA. NEJM 2007;357:

Diagnosis of CMV Giant cell with inclusion body Diagnosis Cytopathology Culture Serologic test (IgG, IgM) Serologic test (IgG, IgM) Measure of viremia Antigenemia assay (pp65 in leukocytes) Antigenemia assay (pp65 in leukocytes) PCR/Hybrid-capture DNA

Treatment of CMV

Prevention of CMV Two main strategies

I. 서론 III. 신장 이식 후 시기별 감염병 IV. 우리나라에서 중요한 기회감염병 V. 결론 Cytomegalovirus 11 Pneumocystis jirovecii 22 Tuberculosis 33 II. 이식 후 감염병의 접근

Epidemiology 5-15% of patients who underwent solid organ TPL developed PCP in the absence of prophylaxis. –Lung, Heart-lung (10 ~ 40%) > Kidney (2 ~ 15%) Incidence may be decreasing with reduction in the use of corticosteroids and adoption of prophylaxis. Gomori methamine silver (GMS) stain of lung tissue

Diagnosis Identification of P. jirovecii from sputum, BAL fluid, lung tissue ; definitive diagnosis Direct Staining, immunofluorescent staining PCR: sensitivity↑, specificity ↓ Plasma beta-D-glucan: high sensitivity (96.4%), specificity (87.8%) in HIV patients Diff-Quik stain Silver Gram stain Immunofluorescent antibody

Treatment TOC Second line

Prophylaxis TMP-SMX (TOC) > Dapsone (2 nd line) –Preventing Toxoplasma and Listeria species –Reducing UTI 80mg TMP/400 mg SMX daily 160 mg TMP/800 mg SMX daily or 3 times weekly Optimal duration; No universal consensus exists

I. 서론 III. 신장 이식 후 시기별 감염병 IV. 우리나라에서 중요한 기회감염병 V. 결론 Cytomegalovirus 11 Pneumocystis jirovecii 22 Tuberculosis 33 II. 이식 후 감염병의 접근

Epidemiology Incidence of Tb after solid organ TPL –20-74 times higher in recipients than in general population High incidence rate of Tb in general population in Korea; 100 case / 100,000 (2011)  Reflecting high incidence of Tb after renal TPL –USA %, Korea %

Risk Factors Risk factors for development of tuberculosis immunosuppressive treatment with OKT3 or anti–T cell Ab diabetes mellitus chronic liver disease coexisting infections (e.g., CMV, PCP, Nocardiosis) CXR lesion suggestive of previous tuberculosis infection

Clinical manifestations Type of tuberculosis infection Diverse, unsuspected sites of tuberculosis infection Gastrointestinal disease: GI bleeding, peritonitis, ulcer Involvement in skin, muscle, the osteoarticular system, the CNS, the genitourinary tract...

Treatment of active Tb Standard regimen in recipients (IDSA/CDC guideline) HREZ for the first 2 months + HR for 4 months Significant interactions between rifampin and immunosuppressive agents Rifampin decreased level of cyclosporine and tacrolimus Some did not recommend rifampin If rifampin is used, cyclosporine or tacrolimus dose should be increased 3-5 fold, serum level should be monitored

Prophylaxis Target - Increased risk of developing active Tb –TST / IGRA test (+) –Radiographic lesions suggestive of prev. history of Tb without Tb treatment Isoniazid (9 mo) – agent of choice

II. 이식 후 감염병의 접근

Conclusion 신장 이식 후 감염병은 이식환자의 중요한 사망원인이자 이식신의 기 능 유지에도 중요한 인자이다. 신이식 후 감염병을 진단할 때는 epidemiologic exposure 와 net state of immunosuppression 을 고려해야 한다. 또한 이식 후 시기별로 한달 이내 / 1-6 개월 사이 / 6 개월 이후에 따라 다른 유형의 감염을 보인다. 면역 저하자에서는 다양한 기회감염이 흔하며, 빠르게 진행할 수 있 어 위험군을 선별하여 예방하고 빠른 진단과 치료를 하는 것이 중요 하다. 특히 우리나라에서 문제가 되는 기회 감염병들을 잘 이해하여 미리 의심하는 것이 이환과 사망을 줄이는 첫 단계이다.