The Efficacy of Rabbit Anti-Thymocyte Globulin for Acute Kidney Transplant Rejection in Patients Using Calcineurin Inhibitor and Mycophenolate Mofetil-Based Immunosuppressive Therapy

Abstract

BackgroundT cell depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney allograft rejection (AR) and is used as first-line therapy in severe AR. Almost all studies investigating the effectiveness of rATG for this indication were conducted at the time when cyclosporine A and azathioprine were the standard of care. Here, the long-term outcome of rATG for AR in patients using the current standard immunosuppressive therapy (i.e., tacrolimus and mycophenolate mofetil) is described.Material/MethodsBetween 2002 to 2012, 108 patients were treated with rATG for AR. Data on kidney function in the year following rATG and long-term outcomes were collected.ResultsOverall survival after rATG was comparable to overall survival of all kidney transplantation patients (P=0.10). Serum creatinine 1 year after rATG was 179 μmol/L (interquartile range (IQR) 136–234 μmol/L) and was comparable to baseline serum creatinine (P=0.22). Early AR showed better allograft survival than late AR (P=0.0007). In addition, 1 year after AR, serum creatinine was lower in early AR (157 mol/L; IQR 131–203) compared to late AR (216 mol/L; IQR 165–269; P<0.05). The Banff grade of rejection, kidney function at the moment of rejection, and reason for rATG (severe or glucocorticoid resistant AR) did not influence the allograft survival.ConclusionsTreatment of AR with rATG is effective in patients using current standard immunosuppressive therapy, even in patients with poor allograft function. Early identification of AR followed by T cell depleting treatment leads to better allograft outcomes.

Comparison of Alemtuzumab and Anti-Thymocyte Globulin Treatment for Acute Kidney Allograft Rejection

“…MMF was started at 1,000 mg twice daily and subsequent dosing was based on C 0 (target C 0 was 1.5-3.0 mg/L). Glucocorticoids were given as an intravenous dose of 100 mg on days 0-3 and followed by a dose of 20 mg/day (days [4][5][6][7][8][9][10][11][12][13][14]. Thereafter, glucocorticoids were tapered off and completely withdrawn around month 4.…”

“…All patients received prophylaxis for Pneumocystis jirovecii (sulfamethoxazole/trimethoprim) and cytomegalovirus (CMV; valganciclovir, except for CMV seronegative recipients with CMV seronegative donors) until the T cell count was >200 × 10 6 /L. Patients with aABMR or mixed type AR could additionally be treated with intravenous immunoglobulins (IVIg), plasma-exchange, or both according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline (9).…”

“…Currently, rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant, recurrent or severe (Banff grade IIA or higher) acute T cell-mediated rejection (aTCMR) (9). Although effective, rATG has several limitations, for instance infusion-related side effects (10-12).…”

Comparison of Alemtuzumab and Anti-thymocyte Globulin Treatment for Acute Kidney Allograft Rejection

“…Currently, rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant, recurrent or severe (Banff grade IIA or higher) acute T cell-mediated rejection (aTCMR) ( 9 ). Although effective, rATG has several limitations, for instance infusion-related side effects ( 10 – 12 ). Alemtuzumab might be an alternative T cell-depleting therapy for AR with fewer infusion-related side effects ( 1 – 5 ).…”

“…Factors that influenced allograft survival were investigated, and we focused on the occurrence of infections, malignancies and autoimmune diseases. Patient-, allograft-, and infection-free survival of alemtuzumab-treated patients were compared with those of patients treated with rATG for AR ( 10 ).…”