Nicol D L, MacDonald A S, Belitsky P, Lee S, Cohen A D, Bitter-Suermann H, Lowen J, Whalen A
Kidney Transplant Service, Victoria General Hospital, Halifax, Nova Scotia, Canada.
Transplantation. 1993 Apr;55(4):841-6. doi: 10.1097/00007890-199304000-00030.
CMV-seronegative recipients of kidneys from CMV-seropositive donors (D+/R+) are at highest risk for developing clinical CMV disease. Even with routine prophylactic use of low-dose acyclovir we had a CMV disease incidence of 26% (5/19) in these patients. Published studies using either acyclovir or CMV hyperimmune globulin (HIG) alone as prophylaxis have also shown clinical disease in 20-30% of D+/R+ patients--less than controls but still significantly greater than in comparable CMV+ recipients (R+). The purpose of this study was to determine whether the risk of primary CMV disease in D+/R- patients was reduced by prophylaxis with combined CMV-HIG and low-dose acyclovir as follows: CMV-HIG (Immuno) 1 ml/kg i.v. immediately prior to transplantation and at 3-week intervals for 6 months; acyclovir 600 mg/day p.o. for 3 months. A total of 361 consecutive renal transplants were studied prospectively. All D+/R- pts (n = 73) received CMV-HIG and acyclovir, the others (91 D+/R+, 74 D-/R+, 123 D-/R-) received only low-dose acyclovir. The incidence of clinical CMV disease, CMV-related graft loss, graft and patient survival, and the influence of ALG and OKT-3 were analyzed and compared between groups. Of the 361 patients only 18 (5%) developed CMV disease, with 5 CMV-related graft losses. CMV disease occurred in only 10% of the D+/R- patients, lower than in previously reported studies. Significantly the incidence was as low as in CMV+ recipients of kidneys from both CMV+ (6%) and CMV- (7%) donors. Use of OKT-3 for steroid-resistant rejection increased the risk of developing CMV disease: 11/50 (22%) receiving OKT-3 developed CMV disease vs. only 7/311 (2%) who did not (P < 0.001); 11/18 (61%) with CMV disease had received OKT-3. ALG induction immunosuppression did not increase the risk of CMV in patients who subsequently received OKT-3. No patient developed CMV disease after discontinuing prophylaxis. There were no complications related to either CMV-HIG or acyclovir use. Compared with all other patients, the D+/R- group had superior graft survival at 1 and 3 years (94% vs. 87% and 86% vs. 74%, P < 0.05) but similar patient survival. Combined CMV-HIG and low-dose acyclovir appear to be better than either agent alone in preventing primary CMV disease in CMV- patients who receive CMV+ kidneys. Low-dose oral acyclovir (600 mg/day) may be as effective in preventing CMV disease as higher-dose prophylactic regimens, at least when accompanied by CMV-HIG.(ABSTRACT TRUNCATED AT 400 WORDS)
接受来自巨细胞病毒血清学阳性供者肾脏的巨细胞病毒血清学阴性受者（D+/R+）发生临床巨细胞病毒疾病的风险最高。即便常规预防性使用低剂量阿昔洛韦，这些患者的巨细胞病毒疾病发病率仍达26%（5/19）。已发表的研究表明，单独使用阿昔洛韦或巨细胞病毒高效价免疫球蛋白（HIG）进行预防时，20% - 30%的D+/R+患者会出现临床疾病——虽低于对照组，但仍显著高于可比较的巨细胞病毒阳性受者（R+）。本研究的目的是确定如下联合使用巨细胞病毒HIG和低剂量阿昔洛韦进行预防，是否能降低D+/R - 患者发生原发性巨细胞病毒疾病的风险：移植前即刻静脉注射巨细胞病毒HIG（免疫球蛋白）1 ml/kg，之后每3周一次，共6个月；口服阿昔洛韦600 mg/天，共3个月。前瞻性研究了连续的361例肾移植患者。所有D+/R - 患者（n = 73）接受巨细胞病毒HIG和阿昔洛韦，其他患者（91例D+/R+、74例D - /R+、123例D - /R - ）仅接受低剂量阿昔洛韦。分析并比较了各组临床巨细胞病毒疾病的发病率、与巨细胞病毒相关的移植物丢失、移植物和患者生存率，以及抗淋巴细胞球蛋白（ALG）和OKT - 3的影响。361例患者中仅18例（5%）发生巨细胞病毒疾病，5例出现与巨细胞病毒相关的移植物丢失。巨细胞病毒疾病仅在10%的D+/R - 患者中发生，低于先前报道的研究。值得注意的是，其发病率与接受来自巨细胞病毒阳性（6%）和巨细胞病毒阴性（7%）供者肾脏的巨细胞病毒阳性受者一样低。使用OKT - 3治疗激素抵抗性排斥反应会增加发生巨细胞病毒疾病的风险：接受OKT - 3治疗的50例中有11例（22%）发生巨细胞病毒疾病，而未接受OKT - 3治疗的311例中仅7例（2%）发生（P < 0.001）；发生巨细胞病毒疾病的18例中有11例（61%）接受过OKT - 3治疗。ALG诱导免疫抑制并未增加随后接受OKT - 3治疗患者发生巨细胞病毒疾病的风险。停止预防后无患者发生巨细胞病毒疾病。未出现与使用巨细胞病毒HIG或阿昔洛韦相关的并发症。与所有其他患者相比，D+/R - 组在1年和3年时的移植物生存率更高（94%对87%以及86%对74%，P < 0.05），但患者生存率相似。联合使用巨细胞病毒HIG和低剂量阿昔洛韦在预防接受巨细胞病毒阳性肾脏的巨细胞病毒阴性患者发生原发性巨细胞病毒疾病方面似乎优于单独使用任何一种药物。低剂量口服阿昔洛韦（600 mg/天）在预防巨细胞病毒疾病方面可能与高剂量预防方案同样有效，至少在联合使用巨细胞病毒HIG时如此。（摘要截选至400字）
