Department of Hospital Pharmacy, Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands; Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
Department of Nephrology, Radboud university Medical center, Postbus 9101, 6500 HB Nijmegen, The Netherlands.
Pharmacol Res. 2021 May;167:105565. doi: 10.1016/j.phrs.2021.105565. Epub 2021 Mar 17.
Breakthrough cytomegalovirus (CMV) disease during valganciclovir prophylaxis is rare but may cause significant morbidity and even mortality. In order to identify patients at increased risk the incidence of CMV disease was studied in a large population of renal transplant recipients who underwent a kidney transplantation in the Radboud University Medical Center between 2004 and 2015 (n = 1300). CMV disease occurred in 31/1300 patients. Multivariate binary linear regression analysis showed that delayed graft function (DGF) (p = 0.018) and rejection (p = 0.001) significantly and independently increased the risk of CMV disease, whereas CMV status did not. Valganciclovir prophylaxis was prescribed to 281/1300 (21.6%) high-risk patients (defined as CMV IgG-seronegative recipients receiving a kidney from a CMV IgG-seropositive donor (D+/R-)). Of these 281 patients, 51 suffered from DGF (18%). The incidence of breakthrough CMV disease in D + /R- patients with DGF was much higher than in those with immediate function (6/51 (11.8%) vs 2/230, (0.9%), p = 0.0006 Fisher's exact test), despite valganciclovir prophylaxis. This higher incidence of CMV disease could not be explained by a higher incidence of rejection (and associated anti-rejection treatment) in patients with DGF. D + /R- patients with DGF are at increased risk of developing CMV disease despite valganciclovir prophylaxis. These findings suggest that underexposure to ganciclovir occurs in patients with DGF. Prospective studies evaluating the added value of therapeutic drug monitoring to achieve target ganciclovir concentrations in patients with DGF are needed.
巨细胞病毒（CMV）突破性疾病在缬更昔洛韦预防中较为罕见，但可能导致严重的发病率，甚至死亡率。为了确定高风险患者，研究人员对 2004 年至 2015 年间在拉德堡德大学医学中心接受肾移植的 1300 例肾移植受者进行了一项大规模人群研究，以确定 CMV 疾病的发生率。31/1300 例患者发生 CMV 疾病。多变量二元线性回归分析表明，延迟移植物功能（DGF）（p=0.018）和排斥反应（p=0.001）显著且独立地增加了 CMV 疾病的风险，而 CMV 状态没有。281/1300（21.6%）高危患者（定义为 CMV IgG 阴性受者接受 CMV IgG 阳性供者的肾脏（D+/R-））接受了缬更昔洛韦预防。在这 281 例患者中，51 例发生 DGF（18%）。尽管进行了缬更昔洛韦预防，但 DGF 患者的 D+/R-患者突破性 CMV 疾病的发生率明显高于肾功能立即恢复的患者（6/51（11.8%）与 2/230（0.9%），p=0.0006Fisher 确切检验）。尽管在 DGF 患者中发生了排斥反应（和相关的抗排斥治疗），但 CMV 疾病的更高发生率无法得到解释。尽管进行了缬更昔洛韦预防，但 DGF 的 D+/R-患者发生 CMV 疾病的风险增加。这些发现表明，DGF 患者接受更昔洛韦的暴露不足。需要前瞻性研究评估治疗药物监测在实现 DGF 患者目标更昔洛韦浓度方面的附加值。
