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Efficacy and safety of low-dose valganciclovir prophylaxis among renal transplant recipients

Year 2020, Volume: 45 Issue: 1, 347 - 351, 31.03.2020
https://doi.org/10.17826/cumj.632257

Abstract

Purpose: Cytomegalovirus (CMV) infection is one of the most common infections observed following kidney transplantations. Transplantations between cytomegalovirus (Immunoglobulin G)-seropositive donor and CMV-seropositive recipient (D+/R+) are considered to be of moderate risk. In our study, we investigated the efficacy of low-dose (450 mg/g) valganciclovir in CMV chemoprophylaxis in renal transplant patients over their first post-transplant year.
Materials and Methods: A total of 68 consecutive patients aged over 18 years who underwent renal transplantation between January 2016 and June 2019 were included in this retrospective study. All patients were administered valganciclovir 450 mg/g, for 100 days. The efficacy of low-dose valganciclovir was determined by whether the patients developed a CMV disease during their first post-transplant year.
Results: Only one patient (n=1/68) (1.5%) developed CMV disease. CMV DNA titer was positive on post-transplant day 134 of the patient who had unexplained loss of GFR. CMV disease-related acute rejection, graft loss, leukopenia, post-transplant diabetes mellitus, opportunistic infection, or patient loss was not observed.
Conclusion: There are many studies comparing CMV prophylaxis with low and standard dose (450 vs. 900 mg/g) valganciclovir treatment in transplant patients. The results of this study show that low-dose valganciclovir is sufficient for the prophylaxis of CMV disease in D+/R+ medium-risk patients without leading to any side effects. Further clinical studies with larger patient participation are needed.

Supporting Institution

The authors declared that this study has received no financial support.

Thanks

The authors have no conflict of interest to declare.

References

  • Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Snydman DR, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 2010;89(7):779-95.
  • Sagedal S, Hartmann A, Nordal KP, Osnes K, Leivestad T, Foss A, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int 2004;66(1): 329-37.
  • Razonable RR, Rivero A, Rodriguez A, Wilson J, Daniels J, Jenkins G, et al. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis 2001;184(11):1461-64.
  • Wiltshire H, Hirankarn S, Farrell C, Paya C, Pescovitz MD, Humar A, et al. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet 2005; 44(5):495-507.
  • Humar A, Limaye AP, Blumberg EA, Hauser IA, Vincenti F, Jardine AG, et al. Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is associated with long-term reduction in cytomegalovirus disease: two-year results of the IMPACT study. Transplantation 2010; 90(12):1427-31.
  • Trevillyan J, Angus P, Shelton E, Whitlam J, Ierino F, Pavlovic J, et al. Electronic estimations of renal function are inaccurate in solid-organ transplant recipients and can result in significant underdosing of prophylactic valganciclovir. Antimicrob Agents Chemother 2013; 57(8):4058-60.
  • Gabardi S, Asipenko N, Fleming J, Lor K, McDevitt-Potter L, Mohammed A, et al. Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients. Transplantation 2015; 99(7):1499-505.
  • Gheith O, Halim MA, Al-Otaibi T, Mansour H, Mosaad A, Atteya HA, et al. Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir. Exp Clin Transplant 2017; 15(Suppl 1):156-63.
  • Halim MA, Al-Otaibi T, Gheith O, Adel H, Mosaad A, Hasaneen AA, et al. Efficacy and Safety of Low-Dose Versus Standard-Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Intermediate-Risk Kidney Transplant Recipients. Exp Clin Transplant 2016;14(5):526-34.
  • Kalil AC, Mindru C, Florescu DF. Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis. Clin Infect Dis 2011;52(3):313-21.
  • Razonable RR, Humar A, Practice AS. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013;13(Suppl 4):93-106.
  • Heldenbrand S, Li C, Cross RP, DePiero KA, Dick TB, Ferguson K, et al. Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients. Transpl Infect Dis 2016; 18(6):904-12.
  • Halim MA, Gheith OA, Makkeya Y, Nagib AM, Atta AF, Emam M, et al. Extended Efficacy of Low-Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Intermediate-Risk Kidney Transplant Recipients: Two-Year Follow-Up. Exp Clin Transplant 2019;17(3):339-43.
  • Xin W, Hui Y, Xiaodong Z, Xiangli C, Shihui W, Lihong L. Effectiveness of Valganciclovir 900mg Versus 450mg for Cytomegalovirus Prophylaxis in Renal Transplantation: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci 2017; 20(0):168-83.
  • Khan S, Fischman C, Huprikar S. Low-dose valganciclovir prophylaxis for cytomegalovirus in intermediate-risk (R+) renal transplant recipients: Single-center experience. Transpl Infect Dis 2017; 19(6):1-3.

Renal transplant alıcılarında düşük doz valgansiklovir profilaksisinin etkinliği ve güvenilirliği

Year 2020, Volume: 45 Issue: 1, 347 - 351, 31.03.2020
https://doi.org/10.17826/cumj.632257

Abstract

Amaç: Sitomegalovirüs (CMV) infeksiyonu, böbrek nakli sonrasında en sık görülen infeksiyonlardan biridir. Sitomegalovirüs (Immunglogulin G) -seropozitif donör ve CMV-seropozitif alıcı ( D+/A+) arasında yapılan nakiller orta riskli kabul edilmektedir. Çalışmamızda renal transplantasyon yapılmış hastalarda nakil sonrası 1 yıllık dönem için düşük doz (450 mg/g) valgansiklovirin CMV kemoprofilaksindeki etkinliğini araştırdık.
Gereç ve Yöntem: Ocak 2016 ile Haziran 2019 tarihleri arasında böbrek nakli yapılmış 18 yaş üzerinde ardışık 68 hasta retrospektif olarak çalışmaya dahil edildi. Tüm hastalara 100 gün süreyle 450 mg/g valgansiklovir tedavisi verildi. Düşük doz valgansiklovirin etkinliği hastaların posttransplant 1 yıl içerisinde CMV hastalığı geçirip geçirmemeleri dikkate alınarak belirlendi.
Bulgular: Sadece bir hastada (n=1/68) (%1,5) CMV hastalığı gelişti. Nakil sonrası 134. günde nedeni açıklanamayan GFR kaybı olan hastanın CMV DNA titresi pozitif geldi. Tüm grupta CMV hastalığı ilişkili akut rejeksiyon, graft kaybı, lökopeni, PTDM, fırsatçı infeksiyon veya hasta kaybı gelişmedi.
Sonuç: Literatürde transplant hastalarında CMV profilaksisi için düşük doz (450 mg/g) valgansiklovir tedavisinin standart doz (900 mg/g) ile karşılaştıran çok sayıda araştırma mevcuttur. Çalışmamızda düşük doz valgansiklovirin D+/A+ orta riskli hastalarda CMV hastalığının profilaksisi için yeterli olduğu ve yan etkiye yol açmadığını gördük. Bu konu ile ilgili geniş hasta katılımlı klinik çalışmalara ihtiyaç vardır.

References

  • Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Snydman DR, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 2010;89(7):779-95.
  • Sagedal S, Hartmann A, Nordal KP, Osnes K, Leivestad T, Foss A, et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int 2004;66(1): 329-37.
  • Razonable RR, Rivero A, Rodriguez A, Wilson J, Daniels J, Jenkins G, et al. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis 2001;184(11):1461-64.
  • Wiltshire H, Hirankarn S, Farrell C, Paya C, Pescovitz MD, Humar A, et al. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet 2005; 44(5):495-507.
  • Humar A, Limaye AP, Blumberg EA, Hauser IA, Vincenti F, Jardine AG, et al. Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is associated with long-term reduction in cytomegalovirus disease: two-year results of the IMPACT study. Transplantation 2010; 90(12):1427-31.
  • Trevillyan J, Angus P, Shelton E, Whitlam J, Ierino F, Pavlovic J, et al. Electronic estimations of renal function are inaccurate in solid-organ transplant recipients and can result in significant underdosing of prophylactic valganciclovir. Antimicrob Agents Chemother 2013; 57(8):4058-60.
  • Gabardi S, Asipenko N, Fleming J, Lor K, McDevitt-Potter L, Mohammed A, et al. Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients. Transplantation 2015; 99(7):1499-505.
  • Gheith O, Halim MA, Al-Otaibi T, Mansour H, Mosaad A, Atteya HA, et al. Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir. Exp Clin Transplant 2017; 15(Suppl 1):156-63.
  • Halim MA, Al-Otaibi T, Gheith O, Adel H, Mosaad A, Hasaneen AA, et al. Efficacy and Safety of Low-Dose Versus Standard-Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Intermediate-Risk Kidney Transplant Recipients. Exp Clin Transplant 2016;14(5):526-34.
  • Kalil AC, Mindru C, Florescu DF. Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis. Clin Infect Dis 2011;52(3):313-21.
  • Razonable RR, Humar A, Practice AS. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013;13(Suppl 4):93-106.
  • Heldenbrand S, Li C, Cross RP, DePiero KA, Dick TB, Ferguson K, et al. Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients. Transpl Infect Dis 2016; 18(6):904-12.
  • Halim MA, Gheith OA, Makkeya Y, Nagib AM, Atta AF, Emam M, et al. Extended Efficacy of Low-Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Intermediate-Risk Kidney Transplant Recipients: Two-Year Follow-Up. Exp Clin Transplant 2019;17(3):339-43.
  • Xin W, Hui Y, Xiaodong Z, Xiangli C, Shihui W, Lihong L. Effectiveness of Valganciclovir 900mg Versus 450mg for Cytomegalovirus Prophylaxis in Renal Transplantation: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci 2017; 20(0):168-83.
  • Khan S, Fischman C, Huprikar S. Low-dose valganciclovir prophylaxis for cytomegalovirus in intermediate-risk (R+) renal transplant recipients: Single-center experience. Transpl Infect Dis 2017; 19(6):1-3.
There are 15 citations in total.

Details

Primary Language English
Subjects Transplantation
Journal Section Research
Authors

Emel Isiktas Sayilar 0000-0002-8824-6560

İhsan Ergun 0000-0003-2066-5512

Publication Date March 31, 2020
Acceptance Date February 4, 2020
Published in Issue Year 2020 Volume: 45 Issue: 1

Cite

MLA Isiktas Sayilar, Emel and İhsan Ergun. “Efficacy and Safety of Low-Dose Valganciclovir Prophylaxis Among Renal Transplant Recipients”. Cukurova Medical Journal, vol. 45, no. 1, 2020, pp. 347-51, doi:10.17826/cumj.632257.