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신장이식 후 감염병
Infectious Disease
in Kidney-Transplant Recipients
신장내과 R3 오동준
I.
서론
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
Prevalence of transplantation in
Korea
연도
소계
고형장기
신장 간장 췌장
782
553
205
1,776 1,137
788
1,739 1,127
총계
심장
폐
11
12
1
323
5
21
-
742
364
8
11
2
1,876 1,251
808
414
12
15
2
2,072 1,431
851
544
10
23
3
2,083 1,403
760
598
12
26
7
2,344 1,674
935
678
29
29
3
2,362 1,752
924
750
18
50
9
2,858 2,211 1,143 950
25
84
7
3,170 2,353 1,237 1,019
23
65
8
3,135 2,472 1,287 1,066
27
73
18
3,798 3,030 1,639 1,210
43
98
35
2000(2.
9~) 1,303
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
질병관리본부, 2011 장기이식통계연보
3,845 3,191 1,763 1,244
36
107
국립장기이식관리센터(KONOS)
37
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
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
Risk evaluation of infection
Donor-derived
infection
Epidemiologic
exposure
Recipientderived
infection
Nosocomial
infection
Community
acquired
infection
Risk of
infection
Net state of
immunosuppr
ession
Risk evaluation of infection
Epidemiologic
exposure
• Immunosuppressive therapy: type,
dose, duration
• Integrity of the mucocutaneous
barrier: catheters, epithelial surfaces
Risk
• Neutropenia, lymphopenia
of
infection
• Metabolic conditions
Net state of
immunosuppr
ession
Uremia, malnutrition, diabetes.
Alcoholism with cirrhosis
• Infection with immunomodulating
viruses
CMV, EB virus, HBV, HCV, HIV
I.
서론
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
Timeline of Infection after Organ
TPL
Fishman JA, NEJM 2007
I.
서론
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
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
• 98-100% (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;357:2601-14
Cytomegalovirus Infection – Indirect effects
Fishman JA. NEJM 2007;357:2601-14
Diagnosis of CMV
Diagnosis
Cytopathology
Giant cell
with inclusion body
Culture
Serologic test
(IgG, IgM)
Measure of viremia
Antigenemia assay
(pp65 in leukocytes)
PCR/Hybrid-capture
DNA
Treatment of CMV
Immunomodul
ation
Antiviral
therapy
• Reduction of immunosuppressive agents
• Ganciclovir (TOC) 5mg/kg twice daily
• For a minimum of 2 -3 weeks or longer if
CMV viremia persists
Prevention of CMV
• Two main strategies
Universal
prophylaxis
• Administration of antiviral medication bef
ore onset
• Used for all patients at risk
• Ganciclovir, valganciclovir
Preemptive
strategy
• Periodic screening for occult CMV viremia
and initiation of early treatment
I.
서론
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
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 (2nd 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
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
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 0.35-1.2%, Korea 4.5- 7.7%
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
Disseminated
33%
Pulmonary
Extrapulmona
51%
ry
16%
• 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
< Latent TB Infection Treatment Regimens >
I.
서론
II. 이식 후 감염병의 접근
III. 신장 이식 후 시기별 감염병
IV. 우리나라에서 중요한 기회감염병
1
Cytomegalovirus
2
Pneumocystis jirovecii
3
Tuberculosis
V. 결론
Conclusion
• 신장 이식 후 감염병은 이식환자의 중요한 사망원인이자 이식신의
기능 유지에도 중요한 인자이다.
• 신이식 후 감염병을 진단할 때는 epidemiologic exposure와 net
state of immunosuppression을 고려해야 한다. 또한 이식 후 시기별
로 한달 이내/ 1-6개월 사이/ 6개월 이후에 따라 다른 유형의 감염
을 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.