Department of Pediatrics (Nephrology), Stanford University School of Medicine, Stanford, CA, USA.
Department of Pediatric Nephrolgy, Schneider Children's Medical Center of Israel, 14 Kaplan St., Petah-Tikva, Israel.
Pediatr Nephrol. 2020 Sep;35(9):1729-1736. doi: 10.1007/s00467-020-04561-z. Epub 2020 May 16.
During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF).
Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels.
Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m vs. 80.48 ± 52.1 ml/min/1.73mp = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms.
There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.
在肾移植过程中，移植肾会发生缺血再灌注损伤，而腺嘌呤核苷是主要的介质。本研究旨在评估氨茶碱作为一种腺嘌呤核苷受体拮抗剂，是否能改善早期移植物功能，降低延迟移植物功能障碍（DGF）和缓慢移植物功能障碍（SGF）的发生率。
这是一项单中心、双盲、安慰剂对照的随机临床试验。来自脑死亡供体的接受肾移植的儿科患者被随机分配到氨茶碱治疗组和生理盐水输注的安慰剂组。主要结局是移植后 5 天的估计肾小球滤过率（eGFR）。次要结局是 DGF/SGF 的发生率和尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平。
23 名患者被随机分配到氨茶碱组，27 名患者被分配到安慰剂组。氨茶碱组与安慰剂组在第 5 天 eGFR、DGF/SGF 发生率或尿 NGAL/Creatinine 水平方面无差异（eGFR 67.39±38.9 ml/min/1.73m 与 80.48±52.1 ml/min/1.73mp=0.32；DGF/SGF 5/23（21.7%）与 3/27（11.1%），p=0.31；尿 NGAL/Creatinine 300.5ng/mg IQR 105.5-1464.5ng/mg 与 425.4ng/mg IQR 140.3-1126.2ng/mg，p=0.95）。在 12 个月时，患者存活率为 100%，移植物存活率为 98%。两组的 12 个月 eGFR 相似。
移植前氨茶碱的应用没有获益。我们的结果受到样本量小的限制，因为样本计算是基于第 5 天 eGFR 的主要结局和 DGF/SGF 的低发生率，这可能使我们无法证明疗效。需要进一步的临床研究来确定氨茶碱在肾移植受者中的任何益处，特别是来自高危供体的益处。
