Infect Chemother.  2009 Apr;41(2):72-77. 10.3947/ic.2009.41.2.72.

Clinical Usefulness of Human Cytomegalovirus Antigenemia Assay after Kidney Transplantation

• Kim T
• Sung H
• Park KT
• Kim SC
• Kim SH
• Choi SH
• Kim YS
• Woo JH
• Park SK
• Han DJ
• Lee SO

• KMID: 2170253
• DOI: http://doi.org/10.3947/ic.2009.41.2.72

Abstract

BACKGROUND
This study was performed to determine the cut-off value and the predictability of symptomatic human cytomegalovirus (HCMV) infection according to the peak value of HCMV antigenemia assay in kidney transplant recipients. MATERIALS AND METHODS: We reviewed the results of HCMV antigenemia assay (Chemicon, CA, USA) in patients who received kidney transplantation at our institution from May 2003 through May 2008, and investigated the existence and the type of HCMV infection by the medical record review. Patients who underwent the test only once during the episode or those who received ganciclovir for more than 48hrs before the test were excluded. The receiver-operator characteristic curve was drawn and the point showing maximum likelihood ratio (LR) was chosen as the cut-off value of symptomatic HCMV infection. RESULTS: A total of 689 episodes were screened and 134 episodes were enrolled. Thirty-three (24.6%) episodes were symptomatic HCMV infection, 23 (17.2%) episodes were associated with HCMV syndrome, and 10 (7.5%) episodes were tissue-invasive diseases. The maximum LR was 7.5 (95% confidence interval, 4.014.2) and the cut-off value was 29.5 cells/200,000 WBC. The sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 91.1%, 71.0%, and 89.3%, respectively. CONCLUSIONS: The cut-off value of symptomatic HCMV infection by the peak value of HCMV antigenemia assay in our study was similar with previous results, although the sensitivity was relatively low.

Keyword

Human cytomegalovirus; Antigenemia; Kidney transplantation

MeSH Terms

Cytomegalovirus
Ganciclovir
Humans
Kidney
Kidney Transplantation
Medical Records
Sensitivity and Specificity
Ganciclovir

Figure

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  Figure 1 Receiver operator characteristic curve of the peak value of human cytomegalovirus (HCMV) antigenemia assay. The likelihood ratio (LR) was highest at point A (LR, 7.5; 95% confidence interval, 4.0-14.2). The peak value of HCMV antigenemia assay in point A was 29.5 cells/200,000 WBC (sensitivity 66.7% and specificity 90.1%).

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  Figure 2 The peak value of human cytomegalovirus (HCMV) antigenemia assay by ganciclovir prophylaxis in patients with symptomatic HCMV infection within 6 months after kidney transplantation. A total of 28 events were enrolled within 6 months. Among them, 5 patients received ganciclovir iv 1.25-10 mg/kg/day for 2 weeks (closed circle) and only one patient received ganciclovir iv 0.625 mg/kg/day for 3 weeks (closed diamond) as primary prophylaxis.

Reference

1. Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007. 357:2601–2614.

2. Holdinka RL. Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Human cytomegalovirus. Manual of clinical microbiology. 2007. 9th ed. Washington DC: ASM Press;1549.

3. Gerna G, Percivalle E, Torsellini M, Revello MG. Standardization of the human cytomegalovirus antigenemia assay by means of in vitro-generated pp65-positive peripheral blood polymorphonuclear leukocytes. J Clin Microbiol. 1998. 36:3585–3589.

4. Mhiri L, Kaabi B, Houimel M, Arrouji Z, Slim A. Comparison of pp65 antigenemia, quantitative PCR and DNA hybrid capture for detection of cytomegalovirus in transplant recipients and AIDS patients. J Virol Methods. 2007. 143:23–28.

5. Machado CM, Dulley FL, Boas LS, Castelli JB, Macedo MC, Silva RL, Pallota R, Saboya RS, Pannuti CS. CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy. Bone Marrow Transplant. 2000. 26:413–417.

6. Ki HK, Sohn KM, Rhee JY, Wi YM, Moon CS, Oh WS, Peck KR, Lee NY, Cho JW, Lee SK, Song JH. Usefulness of cytomegalovirus (CMV) antigenemia assay after liver transplantation. Infect Chemother. 2005. 37:199–207.

7. Niubò J, Pérez JL, Martínez-Lacasa JT, García A, Roca J, Fabregat J, Gil-Vernet S, Martín R. Association of quantitative cytomegalovirus antigenemia with symptomatic infection in solid organ transplant patients. Diagn Microbiol Infect Dis. 1996. 24:19–24.

8. Yang CW, Kim YO, Kim YS, Kim SY, Moon IS, Ahn HJ, Koh YB, Bang BK. Clinical course of cytomegalovirus (CMV) viremia with and without ganciclovir treatment in CMV-seropositive kidney transplant recipients. Longitudinal follow-up of CMV pp65 antigenemia assay. Am J Nephrol. 1998. 18:373–378.

9. Kim CK, Song JH, Kim SM, Peck KR, Oh W, Huh W, Kim YG, Kim SJ, Joh JW, Lee NY, Park CG, Hwang ES, Cha CY, Oh HY. Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation. Transplantation. 2003. 75:2151–2155.

10. Sagedal S, Nordal KP, Hartmann A, Degré M, Holter E, Foss A, Osnes K, Leivestad T, Fauchald P, Rollag H. A prospective study of the natural course of cytomegalovirus infection and disease in renal allograft recipients. Transplantation. 2000. 70:1166–1174.

11. Piiparinen H, Höckerstedt K, Grönhagen-Riska C, Lappalainen M, Suni J, Lautenschlager I. Comparison of plasma polymerase chain reaction and pp65-antigenemia assay in the quantification of cytomegalovirus in liver and kidney transplant patients. J Clin Virol. 2001. 22:111–116.

12. Humar A, Michaels M. AST ID Working Group on Infectious Disease Monitoring. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006. 6:262–274.

13. Kahng KW, Kang CM. Study of cytomegalovirus infection in renal transplant recipients who had IgG CMV antibody in the pretransplantation period. Korean J Nephrol. 1997. 16:123–135.

14. Ki HK, Kim CK, Kim SW, Lee H, Kim S, Peck KR, Oh HY, Joh JW, Song JH. Cytomegalovirus infections after renal transplantation. Korean J Infect Dis. 1999. 31:341–345.

15. van den Berg AP, van der Bij W, van Son WJ, Anema J, van der Giessen M, Schirm J, Tegzess AM, The TH. Cytomegalovirus antigenemia as a useful marker of symptomatic cytomegalovirus infection after renal transplantation-a report of 130 consecutive patients. Transplantation. 1989. 48:991–995.

16. Meyer-Koenig U, Weidmann M, Kirste G, Hufert FT. Cytomegalovirus infection in organ-transplant recipients: diagnostic value of pp65 antigen test, qualitative polymerase chain reaction (PCR) and quantitative Taqman PCR. Transplantation. 2004. 77:1692–1698.

17. Degré M, Kristiansen KI, Rollag H, Holter E, Nordal KP. Detection of human cytomegalovirus (HCMV) pp67-mRNA and pp65 antigenemia in relation to development of clinical HCMV disease in renal transplant recipients. Clin Microbiol Infect. 2001. 7:254–260.

18. Brennan DC, Garlock KA, Singer GG, Schnitzler MA, Lippmann BJ, Buller RS, Gaudreault-Keener M, Lowell JA, Shenoy S, Howard TK, Storch GA. Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients. Transplantation. 1997. 64:1843–1846.