Use of Intravenous Immune Globulin and Rituximab for Desensitization of Highly HLA-Sensitized Patients Awaiting Kidney Transplantation

Abstract

BACKGROUND.: We have shown that high-dose intravenous immune globulin (IVIG; 2 g/kg x2 doses)+rituximab (1 g x2 doses) was effective in lowering anti-human leukocyte antigen (HLA) antibodies and improving rates of transplantation. The aim of this report was to evaluate the efficacy of IVIG+rituximab on reduction of anti-HLA antibodies to a level that was permissive for living donor (LD) or deceased donor (DD) transplantation without incurring the risk of antibody-mediated rejection and immediate graft loss. METHODS.: From July 2006 to February 2009, 76 HLA-sensitized (HS) patients who met strict sensitization criteria received kidney transplants after desensitization using IVIG 2 g/kg (days 1 and 30)+rituximab (1 g, day 15). Parameters evaluated included rates of transplantation, previous transplants, panel reactive antibodies, donor specific antibody, crossmatches (CMXs), patient and graft survival, acute rejection, serum creatinines, and infections. RESULTS.: Seventy-six HS CMX treated patients (31 LD/45 DD) were transplanted. For LD and DD recipients, significant reductions were seen in T-cell flow cytometry CMXs from pretreatment (T cell 183.5+/-98.4 mean channel shifts (MCS) for LD and 162.8+/-41 MCS for DD) to time of transplant (T cell 68.2+/-58 MCS for LD [P<0.00006] and 125+/-49 for DD [P=0.05]), respectively. Time on wait list for DD recipients was reduced from 95+/-46 months to 4.2+/-4.5 months after treatment. Twenty-eight patients (37%) experienced acute rejection (29% C4d/8% C4d). Patient and graft survival up to 24 months was 95% and 84%, respectively. The mean serum creatinines, at 12 and 24 months were 1.5+/-1.1 and 1.3+/-0.3 mg/dL, respectively. Viral infections were seen in six patients. CONCLUSIONS.: IVIG and rituximab seems to offer significant benefits in reduction of anti-HLA antibodies allowing improved rates of transplantation for HS patients, especially those awaiting DD, with acceptable antibody-mediated rejection and survival rates at 24 months.

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“…Some authors have reported good outcomes using rituximab, PEX, and IVIG, which are effective in the treatment of rejection in immunologically high-risk patients. [11][12][13][14][15] These 3 methods were designed to inhibit existing antibodies. Rituximab is a chimeric anti-CD20 (anti-B cell) monoclonal antibody approved for the treatment of lymphoma.…”

“…Good outcomes using rituximab, plasma exchange (PEX), and intravenous immunoglobulin (IVIG) have been reported in immunologically high-risk patients. [11][12][13][14][15] We achieved better outcomes using a unique protocol that combined these methods including the use of retuximub, PEX, and IVIG in patients who were FCXM-positive for both T and B cells (FCXM T+B+). In the present study, we investigated the clinical course of FCXM T+B+ patients to validate our strategy.…”

Transplanting Against Histocompatibility Barriers

“…In these studies rejection rates were 31-59% and patient and graft survival was 96-100% and 75-100% respectively. Four of the studies included rituximab as a part of their pre-transplant conditioning regimens [62][63][64][65]. Despite the addition of rituximab, AMR rates remained high, 37-50% and patient and graft survival were similar to the IVIG alone groups 86-100% and 79-94% respectively.…”

The Impact of Donor Type and Quality on Renal Transplant Outcomes

“…In this cohort, desensitized patients waited for an additional 4.2±4.5 months before receiving a deceased donor graft. Overall graft failure and death at 2 years were 80% and 91% respectively, but almost 30% of graft loss was directly attributed to AMR (Vo, Peng et al 2010). …”