Dept. of Internal Medicine, Nephrology section, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Dept. of Internal Medicine, Nephrology section, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
Br J Clin Pharmacol. 2023 Dec;89(12):3629-3636. doi: 10.1111/bcp.15871. Epub 2023 Aug 16.
Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.
In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.
Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.
This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.
肾移植过程中的缺血再灌注损伤（IRI）与不良结局相关。碱性磷酸酶（AP）是一种具有减轻 IRI 潜力的酶。在此研究之前，尚未在肾移植中进行过测试。本研究旨在评估在活体供肾移植中应用 AP 的安全性和可行性。
在这项双盲、随机、安慰剂对照、单中心的初步研究中，所有符合条件的活体供肾受者均被要求给予知情同意。AP（bRESCAP）或安慰剂在移植手术后 24 小时内静脉输注。主要结局-1 年后的移植物功能-用碘海醇测量的肾小球滤过率（mGFR）表示。术后 7 天内的血清和尿液生物标志物被用作肾功能和损伤的替代标志物。
共纳入 11 例患者，其中 5 例接受 bRESCAP 治疗，6 例接受安慰剂治疗。1 年后，两组的 mGFR 无差异。bRESCAP 组未观察到特定的不良事件。bRESCAP 组在第 7 天尿液损伤生物标志物 CCL14、NGAL 和胱抑素 C 的表达较低，这具有统计学意义。
本研究表明，bRESCAP 治疗在肾移植中是可行的，可能对 IRI 诱导的肾炎症具有抑制作用，且不引起安全性问题。未来的研究将评估 bRESCAP 治疗在 IRI 更为明显的心脏死亡后供肾移植中的效果。
