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Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients.
Transplantation. 2008 Nov 15;86(9):1214-21.
Billing H, Rieger S, Ovens J, Süsal C, Melk A, Waldherr R, Opelz G, Tönshoff B.
Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
BACKGROUND:
Chronic antibody-mediated rejection (CAMR) of renal allografts has
recently been recognized as a defined nosologic entity. The outcome of
CAMR is poor; there is no established treatment protocol for this
condition. We therefore initiated a pilot study on treatment of CAMR
with an antihumoral regimen consisting of high-dose intravenous
immunoglobulin (IVIG) and the chimeric anti-CD20 antibody rituximab.
METHODS: Six pediatric renal transplant recipients with CAMR received
four weekly doses of IVIG (1 g/kg body weight per dose), followed by a
single dose of rituximab (375 mg/m2 body surface area) 1 week after the
last IVIG infusion.
Renal allograft biopsies were evaluated using the
Banff '05 classification. Human leukocyte antigen-specific antibodies
were detected by panel-reactive lymphocytotoxicity and solid phase
ELISA assays. RESULTS: Median glomerular filtration rate during 6
months before intervention dropped by 25 (range, 11-26) mL/min/1.73 m2
(P<0.05) and increased in response to antihumoral therapy by 21 (-14
to +30) 6 months (P<0.05) and by 19 (-14 to +23) mL/min/1.73 m2 12
months (P=0.063) after start of treatment. Glomerular filtration rate
improved or stabilized in 4 patients; the two nonresponders had the
highest degree of transplant glomerulopathy, the highest degree of C4d
deposition in peritubular capillaries and pronounced interstitial
inflammation. The treatment regimen was well tolerated. CONCLUSION:
This pilot study demonstrates that CAMR in pediatric renal transplant
recipients can be treated successfully and safely with a combination of
IVIG and rituximab. This observation should encourage more extensive
studies to evaluate this new treatment strategy.
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