Department of Nephrology, Dialysis and Multiorgan Transplantation, University Hospital, Toulouse, France.
Clin J Am Soc Nephrol. 2011 Nov;6(11):2696-704. doi: 10.2215/CJN.00270111. Epub 2011 Sep 15.
Renal transplant recipients with pre-existing diabetes (PD) have reduced graft survival and increased risk of mortality and ischemic heart disease compared with nondiabetic transplant recipients. To assess the effect of belatacept in this high-risk group, we evaluated outcomes of the subpopulation with PD from previously published BENEFIT and BENEFIT-EXT trials.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis evaluated pooled data from BENEFIT (living donors or standard criteria donors) and BENEFIT-EXT (extended criteria donors). Patients were randomized to receive cyclosporine or a more intensive (MI) or less intensive (LI) belatacept regimen.
Of 1209 intent-to-treat patients, 336 had PD. At 12 months, the belatacept LI arm demonstrated a numerically higher rate of patients surviving with a functioning graft (90.4% MI [103 of 114], 92.8% LI [90 of 97], and 80.8% cyclosporine [101 of 125]), and fewer serious adverse events than cyclosporine or MI patients. Three cases of posttransplant lymphoproliferative disorder were reported in LI patients, one involving the central nervous system. Higher rates (% [95% confidence interval]: 22.8% MI [15.1 to 30.5]; 20.6% LI [12.6 to 28.7]; 14.4% cyclosporine (8.2 to 20.6]) and grades of acute rejection were observed with belatacept. Measured GFR (ml/min per 1.73 m(2), 59.8 MI; 62.5 LI; 45.4 cyclosporine), and cardiovascular risk profile were better for belatacept versus cyclosporine.
In post hoc analysis of patients with PD, patient/graft survival and renal function at 12 months were numerically higher with belatacept versus cyclosporine, but not statistically significant. Further study is necessary to confirm the benefits belatacept may provide in these patients.
与非糖尿病移植受者相比，患有预先存在糖尿病（PD）的肾移植受者移植物存活率降低，死亡率和缺血性心脏病风险增加。为了评估贝那普利特在这一高危人群中的效果，我们评估了先前发表的 BENEFIT 和 BENEFIT-EXT 试验中 PD 亚组的结果。
设计、地点、参与者和测量：一项事后分析评估了 BENEFIT（活体供者或标准标准供者）和 BENEFIT-EXT（扩展标准供者）的汇总数据。患者被随机分配接受环孢素或更强化（MI）或更弱强化（LI）贝那普利特方案。
在 1209 名意向治疗患者中，336 例患有 PD。在 12 个月时，贝那普利特 LI 组显示出具有更高功能移植物存活率的患者数量（MI[103/114]为 90.4%，LI[90/97]为 92.8%，环孢素[101/125]为 80.8%），且严重不良事件发生率低于环孢素或 MI 患者。LI 患者报告了 3 例移植后淋巴增殖性疾病，其中 1 例涉及中枢神经系统。更高的发生率（%[95%置信区间]：MI[15.1 至 30.5]为 22.8%；LI[12.6 至 28.7]为 20.6%；环孢素[8.2 至 20.6]为 14.4%）和急性排斥反应的等级与贝那普利特有关。与环孢素相比，贝那普利特的估算肾小球滤过率（ml/min/1.73m2，59.8 MI；62.5 LI；45.4 环孢素）和心血管风险状况更好。
在 PD 患者的事后分析中，与环孢素相比，贝那普利特在 12 个月时的患者/移植物存活率和肾功能更高，但无统计学意义。需要进一步研究来证实贝那普利特在这些患者中的益处。
