Year : 2014 | Volume
: 25 | Issue : 4 | Page : 819--822
Low-dose rabbit anti-thymoglobin globulin versus basiliximab for induction therapy in kidney transplantation
Himanshu V Patel1, Vivek B Kute1, Aruna V Vanikar2, Pankaj R Shah1, Manoj R Gumber1, Divyesh P Engineer1, Hargovind L Trivedi1,
1 Department of Nephrology and Clinical Transplantation, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, India
2 Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, India
Himanshu V Patel
Department of Nephrology and Clinical Transplantation, Institute of Kidney Diseases and Research Centre, Dr. H. L. Trivedi Institute of Transplantation, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
We conducted a single-center prospective double-arm open-labeled study on kidney transplant patients from 2010 to 2011 to evaluate the efficacy of induction therapy using low, single-dose rabbit-antithymocyte globulin (r-ATG), 1.5 mg/kg on Day 0 (n = 80, 60 males, mean age 35.9 years), versus basiliximab (Interleukin-2 blocker) 20 mg on Days 0 and 4 (n = 20, 12 males, mean age 45.1 years) on renal allograft function in terms of serum creatinine (SCr), rejection and infection episodes and patient/graft survival and cost. Demographic and post-transplant follow-up including immunosuppression was similar in both groups. In the r-ATG group, donors were unrelated (spouse, n = 25), deceased (n = 31) and parents/siblings (others), with a mean HLA match of 1.58. Donors in the basiliximab group were living unrelated (spouse, n = 15) and deceased (n = 5), with a mean HLA match of 1.56. No patient/graft was lost in the r-ATG group over a mean of one year follow-up, and the mean SCr was 1.28 mg/dL with 7.5% acute rejection (AR) episodes; infections were also not observed. In the basiliximab group, over the same period of follow-up, there was 95% death-censored graft survival, and the mean SCr was 1.23 mg/dL with 10% AR episodes. One patient died due to bacterial pneumonia and one succumbed to coronary artery disease; one graft was lost due to uncontrolled acute humoral and cellular rejection. The cost of r-ATG and basiliximab were $600 and $2500, respectively. We conclude that induction immunosuppressive therapy with a low-dose r-ATG may be a better option as compared with basiliximab in terms of graft function, survival and cost benefit in kidney transplant patients.
|How to cite this article:|
Patel HV, Kute VB, Vanikar AV, Shah PR, Gumber MR, Engineer DP, Trivedi HL. Low-dose rabbit anti-thymoglobin globulin versus basiliximab for induction therapy in kidney transplantation.Saudi J Kidney Dis Transpl 2014;25:819-822
|How to cite this URL:|
Patel HV, Kute VB, Vanikar AV, Shah PR, Gumber MR, Engineer DP, Trivedi HL. Low-dose rabbit anti-thymoglobin globulin versus basiliximab for induction therapy in kidney transplantation. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Aug 15 ];25:819-822
Available from: http://www.sjkdt.org/text.asp?2014/25/4/819/135057
Kidney transplantation (KTx) using conventional triple-immunosuppression (IS) and induction practiced worldwide has disadvantages of graft/patient loss due to drug toxicity, infections and malignancies apart from financial burden. Induction therapy with thymoglobulin does result in a lower acute rejection rate, but with a higher risk of infections and malignancies. However, the optimal dose of rabbit anti-thymoglobin (r-ATG) is still not defined despite the clinical use for a long time. The meta-analysis from Cochrane database reported a benefit of r-ATG therapy over inter-leukin-2 (IL-2) receptor antibodies for biopsy-proven acute rejection (BPAR) at one year, but at an increased cost of 75%, an increase in the incidence of malignancy and a 32% increase in cytomegalovirus (CMV) disease.  These complications are due to over-immunosuppression and depletion of peripheral T cells  and low pre-transplant thymic function. 
To reduce the r-ATG-related side-effects, it is useful to explore the potential of a lower dosage of this drug. However, only few studies are reported using induction doses lower than 6 mg/kg, ,,,, and none described total dosages lower than 3 mg/kg.
We aim in our present study to compare r-ATG and basiliximab (IL-2 blocker) for induction IS therapy in KTx recipients in terms of the efficacy and safety of these two drugs.
Materials and Methods
This single-center, prospective, double-arm, open-labeled study was undertaken on KTx recipients from January 2010 to December 2011 to evaluate the effect of induction therapy using a low-dose r-ATG versus basili-ximab on renal allograft function and patient and graft survival.
We studied 100 KTx recipients; group-1 included 80 patients who received r-ATG induction and group-2 included 20 patients who received basiliximab induction IS. All the patients had lymphocyte cross-match negative before KTx. Written informed consent from all patients and approval by the Internal Review Board was obtained. Post-transplant follow-up including immunosuppression was similar in both groups. Their demographics were compared and function was evaluated in terms of SCr, rejection episodes, infections as well as survival.
Immunosuppressive regimen: All patients received induction immunosuppressive therapy with methylprednisolone (500 mg intravenously × 3 days) and r-ATG (Genzyme, Cambridge, USA) 1.5 mg/kg single dose in group-1 or basiliximab (Simulect from Novartis Pharma AG, Basel, Switzerland) 20 mg during kidney transplant surgery and on Day 4 after surgery in group-2. r-ATG was dissolved in 250 mL NaCl 0.9% and administered during a 4-6-h period through a peripheral venous cannula started 30 min before the start of arterial anastomosis. We compared also the cost of both drugs.
The maintenance IS consisted of predniso-lone (20 mg/day, tapered to 5-10 mg/day at 1- 3 months post-transplant and continued thereafter), a calcineurin inhibitor (CNI) [cyclos-porine (CsA) (3 mg/kg/day) or tacrolimus (TaC) (0.06-0.08 mg/kg/day)] and/or mycophenolate mofetil (MMF) (1.5-2 g/day) or azathioprine (AZA) 1-2 mg/kg/day. The doses of AZA and MMF were adjusted according to complete blood counts. The doses of CNI were adjusted according to the serum trough levels (C0), measured by fluorescence polarization immuno-assay (FPIA) technology during the first two to three months; subsequently, adjustments were made only in case of graft dysfunction. This decision was due to financial constraints. Cyclosporine dosing was adjusted to achieve the target C0 concentration of 200-250 ng/mL during the first two to three months post-transplantation, 100-200 ng/mL three to six months post-transplantation and ~100 ng/mL thereafter. Tacrolimus dosing was adjusted to achieve target T0 concentrations of 4-7 ng/mL.
All patients received prophylaxis against CMV, fungal and Pneumocystis jerovicii pneumonia infection. Graft biopsy was performed in cases of acute graft dysfunction to evaluate for possible rejection.
There were 60 male and 20 female recipients in group-1 with a mean age of 35.9 years. The donors for this group were unrelated (spouse, n = 25), deceased (n = 31) and parents/siblings (others) with a mean age of 45.3 years and a mean HLA match of 1.58. There were 12 male and eight female recipients in group-2 with a mean age of 45.1 years and mean donor age of 49.6 years. The donors for this group were living unrelated (spouse, n = 15) and deceased (n = 5), with a mean age of 49.5 years and a mean HLA match of 1.56.
In group-1, no patient/graft was lost over a mean of one year follow-up, and the mean SCr was 1.28 mg/dL with 7.5% acute rejection (AR) episodes. Infections were also not observed.
In group-2, over a mean one year of follow-up, there was 90% patient survival and 95% death-censored graft survival. The mean SCr was 1.23 mg/dL and 10% BPAR episodes were documented. One (5%) patient died due to bacterial pneumonia and one (5%) succumbed to coronary artery disease. One graft was lost due to uncontrolled acute humoral and cellular rejection. All donors underwent laparoscopic donor nephrectomy and none of them developed delayed graft function.
The cost of r-ATG was approximately $600, while the cost of basiliximab was approximately $2500.
Low, single-dose ATG can be used as induction agents in immune-conditioned recipients with better apparent results than using basiliximab induction. We found excellent graft outcome even in deceased donor recipients. The infection rate was not higher than expected using a low-dose r-ATG induction protocol.
Kho et al  reported that patients with end-stage renal disease have significantly lower peripheral T and B cell counts than healthy persons. Ultra-low thymoglobulin schedules deplete peripheral lymphocytes in a dose-dependent manner. The T cell-depleting effect of a total dose of 1.5, 3 and 6 mg/kg r-ATG lasts at least for one week, one month and one year, respectively, after transplantation. With a low dose of 1.5 mg/kg ATG, the patient and graft survival and acute rejection were 90%, 90% and 40%, respectively, with no reported chronic rejection, and infections (bacterial/ viral infections) leading to hospitalization at one year post-transplantation were 100% and 0%. Infections requiring hospitalization were observed in six patients, one included pneumonia due to Klebsiella and E. coli, three with urinary tract infection (UTI) and two with invasive fungal candidiasis. CMV antigenemia occurred in six patients by six weeks post-transplant, and they were all given anti-CMV drugs. Wound-related complications were also observed.
Ravichandran et al  reported that low-dose ATG with rituximab and high-dose sirolimus can be used as induction agents in immune-conditioned recipients with better apparent results than using high-dose induction ATG. Khosroshahi et al  reported that prophylactic administration of a single and low-dose ATG (SangStat, Lyon, France; 4-5 mg/kg) the night before KTx could reduce the risk of acute allograft rejection in renal transplant recipients. As peripheral lymphocyte counts reflect the overall immunosuppressive state, but could not be performed, duChen et al  reported that thymoglobulin (1 mg/kg/d) may improve short-term outcomes compared with basiliximab in patients who had KTx and are at high risk for acute rejection and delayed graft function. However, long-term outcomes are similar with thymoglobulin and basili-ximab to resource limitation. Our report has shown that low-dose ATG is safe and devoid of any deleterious effect on graft and patient survival.
Additional prospective and randomized studies with a greater number of patients and long-term evaluation are warranted to confirm these results and further compare the efficacy of thymoglobulin- and basiliximab-receiving kidney transplants.
We conclude that low-dose r-ATG is a better option as compared with basiliximab in terms of graft function, survival and cost benefit in Ktx patients.
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