全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Thymoglobulin Induction Dosing Strategies in a Low-Risk Kidney Transplant Population: Three or Four Days?

DOI: 10.1155/2010/957549

Full-Text   Cite this paper   Add to My Lib

Abstract:

The optimal dose and duration of rabbit antithymocyte globulin (rATG) induction has not been defined. Methods. We compared the safety and efficacy of 2 dosing strategies, rATG 1.5?mg/kg for 4 days ( ) versus 2?mg/kg for 3 days ( ), in a retrospective, cohort study. Results. Two-year rejection-free survival was 95% in each group ( ). Renal function and infection rates were similar. The incidence of leucopenia was similar, although the 2?mg/kg group was more likely to be thrombocytopenic on day 2 (4% versus 28%, ). Length of stay tended to be longer for the 1.5?mg/kg group ( versus days ). A cost savings of $920 per patient for rATG were seen in the 2?mg/kg group ( ). Conclusions. Shorter, more intense dosing of rATG is safe and effective. The 3-day dose strategy resulted in a clinically shorter length of stay and may result in cost savings. 1. Introduction Induction therapy, using potent immunosuppressive agents in the critical, early period of allograft placement with the goal of decreasing the risk of acute rejection and potentially allowing lower overall intensity of the maintenance immunosuppressive regimen, is common in kidney transplantation. The induction agent of choice, along with dose and duration is controversial, center-specific, and often based on limited clinical data. Rabbit antithymocyte globulin (rATG, Thymoglobulin, Genzyme, Cambridge, MA) is FDA approved for treatment of acute rejection at a dose of 1.5?mg/kg for 7–14 days based on the results of a multicenter, double-blind randomized trial [1, 2]. Although rATG is not currently FDA approved as induction therapy in kidney transplantation, it is the most commonly administered agent for this purpose. Over one-half of the 70% of patients that receive an induction agent at the time of kidney transplantation receive rATG. Induction doses have ranged from 1–6?mg/kg/dose over 1–10 days with a more typical regimen of 1.5?mg/kg for 3–5 days [3–11] with a cumulative target of 4.5–10?mg/kg. In animal models, higher initial doses of shorter duration approximating a human-equivalent dose of 6?mg/kg were associated with more peripheral and central lymphocyte depletion and better allograft survival [12]. In humans, total doses of 5.7?mg/kg on average given as 1.5?mg/kg per day have been shown to produce similar outcomes in high risk recipients who received an average of 10.3?mg/kg [9]. Based on these models the optimal induction dose is felt to approximate 6?mg/kg [4, 7–10, 12]. Higher doses and prolonged duration of induction agents are thought to be associated with an increased risk of infection

References

[1]  Thymoglobulin Prescribing Information, Genzyme, Cambridge, Mass, USA, 2005.
[2]  A. O. Gaber, M. R. First, R. J. Tesi et al., “Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation,” Transplantation, vol. 66, no. 1, pp. 29–37, 1998.
[3]  D. C. Brennan, K. Flavin, J. A. Lowell et al., “A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients,” Transplantation, vol. 67, no. 7, pp. 1011–1018, 1999.
[4]  I. A. Agha, J. Rueda, A. Alvarez et al., “Short course induction immunosuppression with thymoglobulin for renal transplant recipients,” Transplantation, vol. 73, no. 3, pp. 473–475, 2002.
[5]  V. R. Peddi, M. Bryant, P. Roy-Chaudhury, E. S. Woodle, and M. R. First, “Safety, efficacy, and cost analysis of thymoglobulin induction therapy with intermittent dosing based on CD3+ lymphocyte counts in kidney and kidney-pancreas transplant recipients,” Transplantation, vol. 73, no. 9, pp. 1514–1518, 2002.
[6]  T. E. Starzl, N. Murase, K. Abu-Elmagd et al., “Tolerogenic immunosuppression for organ transplantation,” Lancet, vol. 361, no. 9368, pp. 1502–1510, 2003.
[7]  R. J. Stratta, A. K. Sundberg, A. C. Farney, M. S. Rohr, E. L. Hartmann, and P. L. Adams, “Experience with alternate-day thymoglobulin induction in pancreas transplantation with portal-enteric drainage,” Transplantation Proceedings, vol. 37, no. 8, pp. 3546–3548, 2005.
[8]  W. Wong, N. Agrawal, M. Pascual et al., “Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation,” Transplant International, vol. 19, no. 8, pp. 629–635, 2006.
[9]  C. Gurk-Turner, R. Airee, B. Philosophe, D. Kukuruga, C. Drachenberg, and A. Haririan, “Thymoglobulin dose optimization for induction therapy in high risk kidney transplant recipients,” Transplantation, vol. 85, no. 10, pp. 1425–1430, 2008.
[10]  R. B. Stevens, D. F. Mercer, W. J. Grant et al., “Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report,” Transplantation, vol. 85, no. 10, pp. 1391–1399, 2008.
[11]  W. C. Goggins, M. A. Pascual, J. A. Powelson et al., “A prospective, randomized, clinical trial of intraoperative versus postoperative thymoglobulin in adult cadaveric renal transplant recipients,” Transplantation, vol. 76, no. 5, pp. 798–802, 2003.
[12]  X. Préville, M. Flacher, B. LeMauff et al., “Mechanisms involved in antithymocyte globulin immunosuppressive activity in a nonhuman primate model,” Transplantation, vol. 71, no. 3, pp. 460–468, 2001.
[13]  L. Murray, Ed., Drug Topics Red Book, Thomson PDR, Montvale, NJ, USA, 2009.
[14]  D. C. Brennan, K. A. Garlock, G. G. Singer et al., “Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients,” Transplantation, vol. 64, no. 12, pp. 1843–1846, 1997.
[15]  D. C. Brennan, K. A. Garlock, B. A. Lippmann et al., “Control of cytomegalovirus-associated morbidity in renal transplant patients using intensive monitoring and either preemptive or deferred therapy,” Journal of the American Society of Nephrology, vol. 8, no. 1, pp. 118–125, 1997.
[16]  L. C. Racusen, K. Solez, R. B. Colvin et al., “The Banff 97 working classification of renal allograft pathology,” Kidney International, vol. 55, no. 2, pp. 713–723, 1999.
[17]  A. S. Levey, J. P. Bosch, J. B. Lewis, T. Greene, N. Rogers, and D. Roth, “A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation,” Annals of Internal Medicine, vol. 130, no. 6, pp. 461–470, 1999.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133