Concomitant basiliximab with low‐dose calcineurin inhibitors in children post‐liver transplantation

Abstract

Orthotopic liver transplantation (OLT) is effective therapy for end-stage liver disease but immunosuppression with calcineurin inhibitors (CNI) leads to significant nephrotoxicity, resulting in either a reduction of dosage to below the therapeutic level or omission of the drug altogether. Basiliximab (Bx) is a human/mouse chimeric monoclonal antibody that inhibits binding of interleukin-2 (IL-2) to IL-2 receptors and thus prevents proliferation of T cells, which is the main step in the development of acute cellular rejection. The aim of this study was to identify the role of Bx in the prevention of acute cellular rejection and in the reduction of nephrotoxicity in children post-liver transplantation. We evaluated three children (19 months, 22 months, and 11 yr of age; one male, two female) who were treated with Bx post-OLT on compassionate grounds. The indications were: nephrotoxicity in two children, requiring re-transplantation for hepatic artery thrombosis and recurrent giant cell hepatitis, respectively; and nephrotoxicity secondary to chemotherapy for hepatoblastoma in the third child. All patients received 10 mg of Bx, at OLT and on Day 4. Tacrolimus (0.15 mg/kg/day) was started at 48 h (n = 2) and cyclosporin (5 mg/kg/day) at 2 weeks (n = 1). Trough levels of tacrolimus were maintained at 5-8 ng/mL and trough levels of cyclosporin at 100-150 mg/L for the first 3 months. All patients received methylprednisolone (2 mg/kg) with azathioprine (1.5 mg/kg) (n = 2) and/or mycophenolate mofetil (20 mg/kg) (n = 1). The glomerular filtration rate (cGFR) was calculated using the Schwartz formula before and 10 weeks after transplant. Bx was found to be easy to administer and no major side-effects were reported. One child had two episodes of mild acute rejection at 5 and 9 weeks post-OLT and one developed chronic rejection requiring re-transplantation at 9 weeks post-OLT. One child did not develop rejection. The mean pretransplant cGFR was 58.1 (54.6-64.1) mL/min/m2. Within 10 weeks of transplantation, the cGFR had improved by 69% to a mean of 116 (88-157.6) mL/min/m2. To conclude, Bx was well tolerated in all children and had a renal sparing effect. It was effective in preventing early acute rejection, but the combination of Bx and low-dose CNI drugs did not prevent late acute or chronic rejection. Further studies to evaluate the appropriate levels of CNI immunosuppression with Bx are required.

Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

“…Single-center studies suggest that renal function is stable for most pediatric LT recipients 1 to 5 years after transplantation [169][170][171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186] and that only a small subgroup develops progressive deterioration. In a recent multicenter, cross-sectional study of the measured GFR in 397 pediatric patients 1 or more years (mean 5 5.2 years) after LT, 17.6% had a measured GFR < 90 mL/ minute/1.73 m 2 .…”

Current Concepts in Pediatric Liver Transplantation

“…A multicenter adult study comparing daclizumab induction, mycophenolate mofetil, corticosteroids, and delayed reduced‐dose tacrolimus with a standard‐dose tacrolimus and corticosteroids schedule reported less nephrotoxicity with equal efficacy in acute rejection incidence, as well as graft and patient survival 75. A similar study was also done in the pediatric patient population with similar results 76…”

Optimizing use of basiliximab in liver transplantation

“…47,48 The most common cause of ESRD after OLT is CNI-induced nephrotoxicity (75%) followed by progression of underlying renal disease (11%), hepato-renal syndrome (7%), and focal sclerosing glomerulosclerosis (7%). 49 The impact of CNIs on renal function and the fact that early kidney dysfunction is a predictor of late chronic renal failure after OLT, 50 have led to a number of studies exploring the use of antibody induction to delay or minimize CNI exposure [51][52][53][54][55][56] In a prospective, open-label, nonrandomized study using basiliximab induction followed by delayed initiation (median delay 36 hours) and reduced dose (trough level of 5 to 10 ng/mL) of Tac with maintenance MMF and steroid taper, Lin et al 54 demonstrated a "renal-sparing" effect of basiliximab induction in adult living donor OLT. They reported a significantly lower incidence of renal insufficiency at the third post-OLT month in the basiliximab group compared to the control (no induction) group (26% vs 67%) with similar incidence of ACR, CMV infection, and new-onset diabetes mellitus.…”