Rebellato Lorita M, Parker Karen, Everly Matthew J, Briley Kimberly P, Kendrick William, Kendrick Scott, Haisch Carl E, Terasaki Paul I, Bolin Paul
Clin Transpl. 2014:137-42.
The development of donor specific antibodies (DSA) post transplant has been associated with chronic rejection and graft failure. In a longitudinal study, we have shown that increases in DSA precede rejection by months, thus allowing time for intervention. We hypothesized that mycophenolic acid (MPA) dose increases may reduce and/or stabilize DSA strength and also preserve renal function. Thirty stable DSA positive kidney transplant recipients participated in this Institutional Review Board approved, exploratory, open-label, single center study to assess the efficacy of MPA dose escalation in patients with DSA. MPA escalation was well tolerated and most patients were able to take higher doses for at least two years (duration of the study). In addition, MPA escalation is safe and participants had no significant side effects such as cytomegalovirus and BK infections. Long-term allograft survival of the MPA escalation group was superior when compared with the control group (p = 0.018). This pilot study indicates that escalation of MPA is safe and may stabilize DSA. In addition, five-year follow up demonstrates improved long-term survival with MPA escalation compared with DSA positive recipients receiving the standard of care. Additional studies using larger cohorts are warranted.
移植后供体特异性抗体(DSA)的产生与慢性排斥反应和移植物功能衰竭有关。在一项纵向研究中,我们发现DSA水平升高比排斥反应提前数月出现,从而为干预留出了时间。我们推测,霉酚酸(MPA)剂量增加可能会降低和/或稳定DSA强度,并保护肾功能。30名稳定的DSA阳性肾移植受者参与了这项经机构审查委员会批准的探索性、开放标签、单中心研究,以评估DSA患者中MPA剂量递增的疗效。MPA剂量递增耐受性良好,大多数患者能够服用更高剂量至少两年(研究持续时间)。此外,MPA剂量递增是安全的,参与者没有出现如巨细胞病毒和BK感染等明显副作用。与对照组相比,MPA剂量递增组的长期移植物存活率更高(p = 0.018)。这项初步研究表明,MPA剂量递增是安全的,并且可能稳定DSA。此外,五年随访显示,与接受标准治疗的DSA阳性受者相比,MPA剂量递增可改善长期存活率。有必要使用更大的队列进行进一步研究。