Successful renal transplantation with desensitization in highly sensitized patients: a single center experience

Abstract

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.

Keywords: Desensitization; Immunoglobulins, Intravenous; Plasmapheresis, Kidney Transplantation; Rituximab.

Fig. 1

Change in PRA before and after PP/IVIG treatment. Of eight patients who had pretransplant PRA levels ≥20%, seven showed a decrease in PRA levels. The mean decreases in class I and class II PRA levels were 61.5% and 100%, respectively.

Fig. 2

Change in PRA and DSA in patients who received rituximab. In patient 9, the level of class I PRA decreased by 64.2%, the level of class II PRA decreased by 100%, and DSA (anti-A1) became undetectable. In patient 10, both class I and class II PRA levels decreased by 100%, and DSA (anti-A11, anti-A33) became undetectable. The reduction in PRA levels lasted for 2-4 months in both patients.

Fig. 3

Change in peripheral blood CD19 cells in patients who received rituximab. After infusion of rituximab (RTX), CD19⁺ cells in the peripheral blood were selectively depleted, while CD4⁺ or CD8⁺ cells were not affected.

Fig. 4

Change in mean serum creatinine concentration in functioning allografts. Nine patients are currently dialysis free after a median follow-up of 22.6 months (range: 6.9-52.0), and there have been no more AR episodes. The latest serum creatinine concentration is 1.0±0.2 mg/dL (range: 0.7-1.4).