探讨胰岛素目标血糖管理对脑死亡器官捐献供肾炎症反应及移植肾预后的影响。

选取内蒙古包钢医院器官获取组织于2015年7月至2020年7月维护的脑死亡供者50例，采用随机数字表法分为对照组和强化组，每组各25例。所有供者确诊脑死亡后且评估为潜在捐献者时开始进行维护，常规组和强化组24 h平均血糖控制目标范围分别为4.4~10.0 mmol/L和4.4~6.1 mmol/L。记录两组供者开始维护时及器官获取时平均动脉压(MAP)、血管活性药物评分(VIS)、中心静脉血氧饱和度(ScvO₂)、血清乳酸和尿量等血流动力学和组织灌注相关参数，血清肌酐、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和胱抑素C等肾损伤指标，以及炎症因子IL-1β、IL-6、IL-18和TNF-α浓度变化。观察两组供者供肾移植受者住院时间、移植肾原发性无功能(PNF)和移植肾功能延迟恢复(DGF)发生情况，以及术后3、6和12个月估算肾小球滤过率(eGFR)和移植肾1年存活率。

两组供者性别、年龄、原发病、体质指数、维护时间以及开始维护时血白细胞、降钙素原和初始血糖水平差异均无统计学意义(P均>0.05)，维护过程中强化组胰岛素用量高于常规组[(10.5±2.0)和(6.5±2.2)U/h]，维护期间血糖低于常规组[(5.0±1.2)和(8.5±2.8)mmol/L]，差异均有统计学意义(t＝6.727和5.745，P<0.05)。开始维护时，两组MAP、VIS、血清乳酸、ScvO₂、尿量、IL-1β、IL-6、TNF-α、IL-18、血清肌酐、NGAL和胱抑素C水平差异均无统计学意义(P均>0.05)。器官获取时，强化组VIS、IL-1β、IL-6、TNF-α、IL-18、NGAL和胱抑素C水平均低于常规组，差异均有统计学意义(t＝3.71、4.29、4.18、5.41、4.41、2.43和2.05，P均<0.05)。常规组和强化组供者均分别捐献肾脏50例，均成功移植。两组受者均未发生PNF，移植肾术后1年存活率均为100%。常规组和强化组受者DGF发生率分别为30%(15/50)和12%(6/50)，差异有统计学意义(χ²＝4.883，P<0.05)。强化组受者术后3个月eGFR优于常规组受者，差异有统计学意义(t＝3.998，P<0.05)；两组受者术后6和12个月eGFR差异无统计学意义(P均>0.05)。

脑死亡器官捐献供者维护期间强化胰岛素目标血糖管理，将血糖控制于4.4~6.1 mmol/L，有助于减轻供肾炎症反应和肾损伤，降低肾移植术后DGF发生率。

This research aims to study the impacts of target blood glucose control with insulin therapy on donor kidney inflammatory response and prognosis of transplanted kidney from donation after brain death (DBD).

Fifty DBD donors maintained by organ procurement organization of Inner Mongolia Baogang Hospital from July 2015 to July 2020 were selected as study subjects. The fifty donors were divide into control group (n=25) and strength group (n=25), with random number table method. Maintenance was initiated after all donors were diagnosed with brain death and assessed as potential donors, and the mean 24 h target range of glucose control was 4.4 to 10.0 mmol/L and 4.4 to 6.1 mmol/L in the control and strength groups, respectively. At the beginning of organ maintenance and donation, the parameters of hemodynamics and tissue perfusion including arterial pressure (MAP), vasoactive drug score (VIS), central venous oxygen saturation (ScvO₂), serum lactic acid and urine volume, and the renal injury indexes including serum creatinine, neutrophil gelatinase-associated lipid carrier protein (NGAL) and Cystatin-C as well as changes in the concentration of inflammatory cytokines, including IL-1β, IL-6, IL-18 and TNF-α were recorded. Then the hospital stay, and the primary nonfunction (PNF) and delayed graft function of transplant kidney as well as postoperative estimated glomerular filtration rate (eGFR) at 3, 6 and 12 months and 1-year survival rates of transplanted kidneys in the two groups were observed.

There were no significant differences in sex, age, primary disease, body mass index, maintenance time, white blood cell, procalcitonin and initial blood glucose levels between the two groups (all P>0.05). Insulin dosage during maintenance in the strength group was higher than that in the control group [(10.5±2.0) and (6.5±2.2) U/h], and blood glucose during maintenance was lower than that in the control group [(5.0±1.2) and (8.5±2.8) mmol/L], which has statistical significance (t=6.727 and 5.745, all P<0.05). At the beginning of maintenance, there were no significant differences in MAP, VIS, serum lactic acid, ScvO₂, urine volume, IL-1β, IL-6, TNF-α, IL-18, serum creatinine, NGAL and Cystatin-C levels between two groups (all P>0.05). At the time of donation, VIS, IL-1β, IL-6, TNF-α, IL-18, NGAL and cystatin-C levels in the strength group were significantly lower than those in the control group (t=3.71, 4.29, 4.18, 5.41, 4.41, 2.43 and 2.05, all P<0.05). Fifty donor kidneys were obtained in the control and strength groups, respectively, and all of them were successfully transplanted. No PNF occurred in both groups, and the 1-year survival rate after kidney transplantation was 100%. The incidence of DGF was 30% (15/50) in the control group and 12.0% (6/50) in the strength group, and the difference was statistically significant (χ²=4.883, P<0.05). The eGFR of the strength group was better than that of the control group 3 months after surgery, the difference was statistically significant (t=3.998, P<0.05). There was no significant difference in eGFR between the two groups at 6 and 12 months after surgery (all P>0.05).

During the maintenance of donors from DBD, the enhancement of target blood glucose control with insulin therapy and the control of blood glucose between 4.4 to 6.1 mmol/L can alleviate donor nephritis and kidney injury, and reduce the incidence of DGF after kidney transplantation.