BK 바이러스 이식 신병증에서 바이러스의 정량 측정과 Cidofovir 치료 = Quantitative Viral Load Monitoring and Cidofovir Therapy in BK Virus Nephropathy

다국어 초록 (Multilingual Abstract)

Background:BK virus nephropathy (BKVN) has been increasingly recognized as an important cause of renal transplant dysfunction, but no specific antiviral therapy is currently available. Furthermore, a method evaluating the degree of viral infection has not been developed yet. Recently, there have been several case reports in which BKVN was successfully treated with cidofovir injection. In the current study, we report a case with BKVN successfully treated with cidofovir injection. In addition, we assessed the usefulness of quantitative viral load monitoring using a competitive polymerase chain reaction (PCR) in the treatment of BKVN.
Methods:A renal allograft recipient with BKVN was injected with cidofovir. To monitor BK viral load in urine and plasma, we developed a competitive PCR assay and followed the patient prospectively.
Results:A 49 year old renal transplant recipient developed a progressive rise in serum creatinine reaching 1.9 mg/dL at 15 months post-transplantation. Subsequently, the patient was diagnosed as BKVAN by allograft biopsy. At this time, BKV DNA was detected in plasma and urine. Despite a reduction of the dose of mycophenolate mofetil, serum creatinine continued to rise, which prompted the initiation of cidofovir trial. The patient was given intravenous cidofovir. After cidofovir treatment, BK virus associated findings disappeared on repeat biopsy, and BK virus in plasma was decreased to the undetectable level. For 7 months after cidofovir treatment, her renal function remained stable.
Conclusion:Cidofovir therapy may be effective in the treatment for BKVN. Viral load in plasma reflected well the clinical and pathological course of the BK virus infection.

국문 초록 (Abstract)

배 경:BK 바이러스 신병증으로 인한 이식신의 소실은 최근 증가하고 있으나, 아직 항바이러스 약제가 없고, 또한 BK 바이러스 감염정도의 변화를 관찰할 수 있는 방법도 없다. 최근 cidofovir의 항 BK 바이러스 효과가 소수의 환자에서 보고 되었으며, 또한 BK 바이러스 신병증의 정도는 혈청 혹은 소변의 BK바이러스 DNA 양과 연관이 있다는 연구결과가 외국에서 보고되었다. 이에 저자들은 cidofovir를 BK 바이러스 신병증 환자 1예에서 투여하고 환자의 혈액과 소변에서 BK 바이러스 DNA를 정량적 측정치로 추적 관찰한 경험을 보고하고자 한다.
방 법:Cidofovir를 BK 바이러스 신병증 환자 1예에서 투약하고 환자의 혈액과 소변에서 BK virus의 DNA를 경쟁적 중합효소연쇄반응을 이용한 정량적 측정치로 추적 관찰하였다.
결 과:대상 환자는 49세 여환으로, 15개월째 혈중 크레아티닌이 1.9 mg/dL로 상승되어 이식신 조직 검사를 시행하였고, BK 바이러스 감염에 의한 신병증으로 진단되었다. 이때 혈청 BK 바이러스 수는 5 copies/µL였고, 소변에서는 5.5×105 copies/µL이었다. 면역 억제제 감량에도 불구하고 신이식 18개월 후 혈청 크레아티닌은 2.4 mg/dL로 증가하였고 혈청 BK 바이러스 수도 9 copies/µL로 증가하여 cidofovir를 정맥 투여하였고, 이 후 신조직에서 BK 바이러스에 의한 병변과 혈청 BK 바이러스는 소실되었다. Cidofovir 치료 후 혈청 크레아티닌 증가도 안정되었다.

참고문헌 (Reference)

• 1 "이식신에 발생한 Polyoma Virus 간질성 신염 1예" 18 : 1017-1021, 1999
• 2 "Vistide Drug Information" Gilead Sciences Inc. USA
• 3 "Treatment of refractory BK virus-associated nephropathy with cidofovir" 3 : 186-191, 2003
• 4 "Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir" 26 : 347-350, 2000
• 5 "The use of vidarabine in the treatment of human polyomavirus associated acute haemorrhagic cystitis" 7 : 481-483, 1991
• 6 "Retinoic acid suppresses polyoma virus transformation by inhibiting transcription of the c-fos proto-oncogene" 9 : 3557-3563, 1994
• 7 "Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults" 75 : 105-112, 2003
• 8 "Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients" 347 : 488-496, 2002
• 9 "Prospective stu dy of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients" 37 : 578-86, 1984
• 10 "Polyomavirus infection of renal allograft recipients : from latent infection to manifest disease" 10 : 1080-1089, 1999
• 11 "Polyomavirus BK nephropathy : a (re-) emerging complication in renal transplantation" 2 : 25-23, 2002
• 12 "Polyomavirus BK infection in pediatric kidney-allograft recipients : a single-center analysis of incidence, risk factors, and novel therapeutic approaches" 75 : 1266-1270, 2003
• 13 "Polyomavirus BK DNA quantification assay to evaluate viral load in renal transplant recipients" 28 : 265-274, 2003
• 14 "New human papova virus(BK)isolated from urine after renal transplantation" 1 : 1253-, 1971
• 15 "Human polyoma virus- associated interstitial nephritis in the allograft kidney" 67 : 103-109, 1999
• 16 "Human polyoma virus in renal allograft biopsies : morphological findings and correlation with urine cytology" 30 : 970-977, 1999
• 17 "Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients" 68 : 1279-1288, 1999
• 18 "Clinical course of polyoma virus nephropathy in 67 renal transplant patients" 13 : 2145-2151, 2002
• 19 "BK virus infection in a kidney allograft diagnosed by needle biopsy" 26 : 671-673, 1995
• 20 "BK transplant nephropathy successfully treated with cidofovir" 18 : 1013-1014, 2003
• 21 "Activation of human polyomavirus infection-detection by cytologic technics" 74 : 326-332, 1980
• 22 "A serological investigation of BK virus and JC virus infections in recipients of renal allografts" 158 : 176-181, 1988