Optimal Dose of Thymoglobulin for Induction Therapy in High Risk Kidney Transplant Recipients

Yaerim Kim; Seong Sik Kang; Woo Yeong Park; Kyubok Jin; Sung Bae Park; Ui Jun Park; Hyoung Tae Kim; Seungyeup Han

doi:10.4285/jkstn.2016.30.2.82

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Kim, Kang, Park, Jin, Park, Park, Kim, and Han: Optimal Dose of Thymoglobulin for Induction Therapy in High Risk Kidney Transplant Recipients

Original Article

J Korean Soc Transplant 2016;30(2):82-85.

Published online: 19 January 2016

DOI: https://doi.org/10.4285/jkstn.2016.30.2.82

Optimal Dose of Thymoglobulin for Induction Therapy in High Risk Kidney Transplant Recipients

Yaerim Kim, M.D.^1,², Seong Sik Kang, M.D.^1,², Woo Yeong Park, M.D.^1,², Kyubok Jin, M.D.^1,², Sung Bae Park, M.D.^1,², Ui Jun Park, M.D.^2,³, Hyoung Tae Kim, M.D.^2,³, Seungyeup Han, M.D.^1,^2,

¹Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea

²Keimyung University Kidney Institute, Daegu, Korea

³Department of Surgery, Keimyung University School of Medicine³, Daegu, Korea

Corresponding author: Seungyeup Han Department of Internal Medicine, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea Tel: 82-53-250-7399, Fax: 82-53-253-7976 E-mail: hansy@dsmc.or.kr

Received 8 March 2016 Revised 13 May 2016 Accepted 19 May 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Thymoglobulin has been used for induction therapy to prevent acute rejection and delayed graft function (DGF) in kidney transplant patients. However, the usual dose of thymoglobulin is considered to be related with frequent infection. We compared the efficacy and safety of low-dose thymoglobulin to high-dose treatment in high risk recipients with kidney transplantation.

Methods:

Twenty-one kidney transplant recipients underwent induction treatment with thymoglobulin and were divided into two groups: patients treated with low-dose (<6.0 mg/kg) and high-dose thymoglobulin (≥6.0 mg/kg). All patients showed one or more risk factors for acute rejection or DGF. The risk factors were re-transplantation, recipient or donor age over 60 years, human leukocyte antigen full mismatch, and panel-reactive antibody more than 50%. We compared incidence of acute rejection, infection, hematologic complications, and graft survival between two groups.

Results:

The demographic characteristics of the two groups were comparable. Mean follow-up duration was 11.9±4.3 months, and cumulative thymoglobulin dosage was 6.3±1.6 mg/kg. The incidence rates of acute antibody-mediated rejection (AMR), DGF and infectious events as cytomegalovirus disease, or urinary tract infection were not significantly different between the two groups. Neutropenia occurred more frequently in the high-dose thymoglobulin group, but there was no statistically significant difference. The rate of graft loss were similar between the two groups.

Conclusions:

There were no differences in graft survival, infectious disease, and hematologic problems between the two groups. We suggest to lower the dose of thymoglobulin to less than 6 mg/kg for prevent acute AMR and DGF in high risk patients.

Keywords: Immunosuppressive agents, Kidney transplantation, Thymoglobulin

REFERENCES

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2). Lentine KL., Schnitzler MA., Xiao H., Brennan DC. Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 study participants. Trials. 2015. 16:365.

3). Brennan DC., Daller JA., Lake KD., Cibrik D., Del Castillo D. Thymoglobulin Induction Study Group. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med. 2006. 355:1967–77.

4). Chen G., Gu J., Qiu J., Wang C., Fei J., Deng S, et al. Efficacy and safety of thymoglobulin and basiliximab in kidney transplant patients at high risk for acute rejection and delayed graft function. Exp Clin Transplant. 2013. 11:310–4.

5). Sancho Calabuig A., Gavela Martinez E., Kanter Berga J., Beltran Calatan S., Avila Bernabeu AI., Pallardo Mateu LM. Safety and efficacy of induction treatment with low thymoglobulin doses in kidney transplantation from expanded-criteria donors. Transplant Proc. 2015. 47:50–3.

6). Clesca P., Dirlando M., Park SI., Garcia R., Ferraz E., Pinheiro-Machado PG, et al. Thymoglobulin and rate of infectious complications after transplantation. Transplant Proc. 2007. 39:463–4.

7). Laftavi MR., Alnimri M., Weber-Shrikant E., Kohli R., Said M., Patel S, et al. Low-dose rabbit antithymocyte globulin versus basiliximab induction therapy in low-risk renal transplant recipients: 8-year follow-up. Transplant Proc. 2011. 43:458–61.

8). Laftavi MR., Patel S., Soliman MR., Alnimri M., Kohli R., Said M, et al. Low-dose thymoglobulin use in elderly renal transplant recipients is safe and effective induction therapy. Transplant Proc. 2011. 43:466–8.

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Table 1.

Comparison of demographic characteristics by thymoglobulin dosage

Characteristic	Low-dose group^a (n=8)	High-dose group^b (n=13)	P-value
Thymoglobulin dose (mg/kg)	4.64±0.22	7.31±0.26	0.000
Follow-up duration (mo)	9.8±1.53	13.2±1.06	0.074
Recipient age (yr)	55.0±2.24	50.6±3.62	0.586
Donor age (yr)	49.1±3.41	43.4±3.63	0.231
Recipient male, sex	2 (25.0)	7 (53.8)	0.367
Deceased donor	7 (87.5)	11 (84.6)	1.000
DSA (+)	3 (42.9)	4 (57.1)	1.000
Re-transplantation	3 (37.5)	3 (23.1)	0.631
Recipient age ＞60 yr	2 (25.0)	3 (23.1)	1.000
Donor age ＞60 yr	0	2 (15.4)	0.505
HLA full mismatch	0	4 (30.8)	0.131
PRA I or II ＞50%	6 (75.0)	5 (38.5)	0.183
PRA I ＞50%	2 (25.0)	4 (30.8)	1.000
PRA II ＞50%	4 (50.0)	2 (15.4)	0.146
Serum creatinine (mg/dL)	1.27±0.21	1.45±0.39	0.885

Data are presented as mean±SD or number (%).

Abbreviations: DSA, donor specific antibody; HLA, human leukocyte antigen; PRA, panel-reactive antibody.

^a Low-dose group: thymoglobulin ＜6.0 mg/kg;

^b High-dose group: thymoglobulin ＞6.0 mg/kg.

Table 2.

Comparison of outcomes between low-dose and high-dose groups

Variable	Low-dose group^a (n=8)	High-dose group^b (n=13)	) P-value
Delayed graft function	1 (12.5)	5 (38.5)	0.336
Antibody-mediated rejection	3 (37.5)	1 (7.7)	0.253
Cytomegalovirus infection	4 (50.0)	5 (38.5)	0.673
Urinary tract infection	2 (25.0)	4 (30.8)	1.000
Lymphocele	0	1 (7.7)	1.000
Neutropenia	5 (62.5)	11 (84.6)	0.325
Thrombocytopenia	3 (37.5)	4 (30.8)	0.557
Graft loss	0	1 (7.7)	1.000

Data are presented as number (%).

^a Low-dose group: thymoglobulin ＜6.0 mg/kg;

^b High-dose group: thymoglobulin ≥6.0 mg/kg.

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