Long-Term Outcomes After Treatment of Chronic and Late Renal Antibody Mediated Rejection With IVIg and Rituximab.

Abstract

Aim: Chronic and late antibody mediated rejection (clAMR) are the major causes of premature renal allograft loss and appear refractory to current therapies with graft loss occurring in up to 50% at 1 year. We aimed to determine long-term graft survival in patients with combined clAMR treated with IVIg and Rituximab and the predictors of graft failure. Methods: Patients >6 months post-transplant with at least 3 years follow-up since clAMR diagnosis were included if they had biopsy evidence of both late AMR defined by peritubular capillaritis (PTCitis) and chronic AMR defined by Banff criteria including presence of at least one donor specific antibody (DSAb). Patients received high dose IVIg (1gm/kg) monthly for 3 months followed by repeat biopsy. Those with persistent PTCitis received a single dose of rituximab (500mg) and further IVIg. Outcomes to 5 years are reported. Results: 24 patients were included. Their mean age was 43.5yrs, 50% were male. The median (range) time from transplant to clAMR diagnosis was 59 (7-267) months and the median (range) time from diagnosis to analysis was 60 (40.5-60) months. 22 were primary grafts. 8 were deceased donor, 14 live donor and 2 were simultaneous kidney and pancreas transplants. 13 had an early rejection episode. DSAb were class I in 5, class II in 15 and both in 4. Eight had positive C4d staining on the initial biopsy. Five-year graft survival from clAMR diagnosis was 75%. At clAMR diagnosis eGFR was significantly lower (mean difference 15ml/min, p=0.009) and urine protein to creatinine ratio significantly higher (median difference 0.12gm/mmol, p=0.008) in those who developed graft failure relative to those who did not. Individually or grouped no acute nor chronic Banff parameter was different between those with and without graft loss, nor was class or MFI of DSAb. Conclusion: Graft survival in clAMR is governed by the degree of graft dysfunction at diagnosis. The graft survival of patients in the current cohort are superior to those described in previous reports suggesting that this treatment regimen warrants randomised study to further assess efficacy.