BK virus infection after Kidney transplantation 신장내과 R1. 김 명

Kidney transplantation

Deceased-donor (formerly known as cada veric) transplantation living-donor transplantation –genetically related (living-related) –non-related (living-unrelated) transplants Kidney transplantation

Treatment of choice in ESRD Better 5YSR, QOL than ESRD Opportunistic infection occurs due to Immunosuppresive therapy –BK virus, CMV, Herpes, … Kidney transplantation

Polyomavirus family. Double strand DNA JC virus, simian virus Ubiquitous virus 1ry infection -> remain uroepithelium Seroprevalence - over 90%, reactivate periodically 5-10% of urine in Immunocompetent adults asymptomatically removed BK virus Infection

-Icosahedral with double circular chain -Type I BKV 70-80%, Type IV 12-20% -reactivated latent polyomavirus disease in immunosuppresive patients(viral activation in pregnancy, DM, KT -PCR 로 확인, urine cytology 에서 decoy cell 관찰 BK virus

Polyomavirus family. Double strand DNA JC virus, simian virus Ubiquitous virus 1ry infection -> remain uroepithelium Seroprevalence - over 90%, reactivate periodically 5-10% of urine in Immunocompetent adults asymptomatically removed BK virus Infection

1ry BKV infection 은 4-5 세 때 발생. airborne 전파. mild or no symptom. fecal to oral route, urinary-oral route Blood transfusion, vertical transmission 한번 감염되면 kidney tubular epithelium, GU tract 에 잠복. 인구의 90% 이상이 BKV 에 감염되어있음. 면역능력있는 성인에서 주기적으로 재활성화되고 무증상적으로 제거됨. 임신 여성의 25% 에서 소변에서 검출

Human renal proximal tubular epithelial cells(HRPTEC) are the main natural tarket of BKV infection Studies employing Vero cells derived from the kidney of an African green monkey - BK virus enter target cells via caveolae-mediated endocytosis Experiments with 1ry HRPTEC - depletion of cholesterol, Caveolin-1 levels by caveolin-1 siRNA inhibit cellular infection by BKV

interstitial nephritis a/w BKV infection - acute cellular rejection 과 구분하기 힘듦 Ascending infection along uroepithelium - treteral stenosis, allograft obstruction 유발 higher level of BKV a/w hemorrhagic cystitis, BKV nephropathy

Diagnosis of BKV Decoy cells - BKVN pts 의 urine cytology 에서 검출. BKVN diagnosis 에 있어서 low positive predictive value(29%) BK viruria> 10^7 copies/ml, viremia > 10^4 copies/ml - criteria for diagnosing BKVN transplant kidney biopsy - G/S for diagnosing BKVN

KT 환자에서 BKN 유발. graft loss 가능. BMT 환자에서 hemorrhagic cystitis 가능 Disease 재활성화는 SLE, AIDS, solid organ transplant 에서 관찰 Level of BK viruria 는 면역저하 정도와 연관. viral replication 은 재감염보다는 지속감염의 재활성화와 연관 Acute T-cell mediated rejection 이 sustained BK viruria 와 연관. BKV 는 extrarenal disease( 폐렴, 뇌염, 간염, 망막염, 모세 혈관누출증후군, 암 ) 과 관련성 적음.

cyclosporine, azathioprine - BKN was forgotten 1990s, 3 세대 면역억제제 소개 후 BKN 1-10% of KT pts. Emergence of this opportunistic infection coincided with the reduction in the incidence of acute rejection after KT BKV screening 이 면역억제를 단계적으로 감소하는데 있 어서 중요한 지표

organ, organ donor factor: HLA mismatch, mechanical injury, ischemic reperfusion, abscence of HLA-C7, female sex, older age(>60), african-american recipient factor: 면역억제 치료, 낮은 BKV Ab titer, HLA, ABO mismatch, HLA-B44, HLA-DR no matching, CMV, delayed graft function, DM, male sex, White, Asian race modulation factor: ureteral stent, steroid 노출력, tacrolumus,mycophenolate high drug level, Low T cell response, BKN 으로 graft loss 후 재이식 most accepted RF: immunosuppressive Tx

BKVN treatment principal - reduction in immunosuppression discontinuation of immunosuppresive agent, steroid avoidance

cidofovir - decreases CMV replication by inhibiting viral DNA polymerase Leflunomide - undergoing this treatment must have laboratory tests once a month for blood counts and liver function, and every 2 weeks for BKV loads. Fluoroquinolones - inhibit bacterial replication by inhibiting type II topoisomerases and have activity against BKV helicase –when BKN has already been established, fluoroquinolones may not be effective IVIG - available preparations of IVIG contain high titers of neutralizing antibodies against BKV. It has direct neutralizing activity, although it is not enough to limit BKV replication

Screening, management of KT

urine cytology for decoy cells evry 2 weeks in 1st 3 months. monthly until month 6, then every 3 months to 2 years, annually until 5 years after KT

It would allow sufficient reconstitution of specific T cells against BKV to control replication and infection and, by maintaining an adequate level of immunosuppression, graft rejection risk would be minimal