Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection

Abstract Background Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. Methods To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF’17 classification, was identified. Results We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. Conclusions Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. Trial registration Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance.

Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients