Collins Michael G, Fahim Magid A, Pascoe Elaine M, Hawley Carmel M, Johnson David W, Varghese Julie, Hickey Laura E, Clayton Philip A, Dansie Kathryn B, McConnochie Rachael C, Vergara Liza A, Kiriwandeniya Charani, Reidlinger Donna, Mount Peter F, Weinberg Laurence, McArthur Colin J, Coates P Toby, Endre Zoltan H, Goodman David, Howard Kirsten, Howell Martin, Jamboti Jagadish S, Kanellis John, Laurence Jerome M, Lim Wai H, McTaggart Steven J, O'Connell Philip J, Pilmore Helen L, Wong Germaine, Chadban Steven J
Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, SA, Australia; Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; Australasian Kidney Trials Network, Centre for Health Services Research, University of Queensland, Brisbane, QLD, Australia.
Australasian Kidney Trials Network, Centre for Health Services Research, University of Queensland, Brisbane, QLD, Australia; Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Lancet. 2023 Jul 8;402(10396):105-117. doi: 10.1016/S0140-6736(23)00642-6. Epub 2023 Jun 18.
Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF.
BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488).
Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48).
Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation.
Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.
移植肾功能延迟（DGF）是尸体供肾移植的主要不良并发症。通常会给接受移植的患者静脉输液，以维持血管内容量并优化移植肾功能。生理盐水（0.9%氯化钠）被广泛使用，但由于其高氯含量可能会增加发生DGF的风险。我们旨在验证以下假设：使用平衡的低氯晶体溶液（Plasma-Lyte 148）而非生理盐水可降低DGF的发生率。
BEST-Fluids是一项务实的、嵌入登记系统的、多中心、双盲、随机对照试验，在澳大利亚和新西兰的16家医院进行。接受尸体供肾移植的任何年龄的成人和儿童均符合条件；接受多器官移植或体重不足20 kg的患者被排除。在手术期间及移植后48小时内，使用适应性最小化算法将参与者随机分配（1:1）至静脉输注平衡晶体溶液（Plasma-Lyte 148）或生理盐水组。试验用液体装在相同的袋子中，临床医生确定液体量、输注速度和停用时间。主要结局为DGF，定义为移植后7天内接受透析。所有同意并接受移植的参与者均纳入主要结局的意向性分析。对所有随机分配的、开始手术并接受试验用液体的合格参与者进行安全性分析，无论他们是否接受了移植。本研究已在澳大利亚新西兰临床试验注册中心（ACTRN12617000358347）和美国国立医学图书馆临床试验数据库（ClinicalTrials.gov，NCT03829488）注册。
2018年1月26日至2020年8月10日期间，808名参与者被随机分配至平衡晶体溶液组（n = 404）或生理盐水组（n = 404）并接受了移植（512名[63%]为男性，296名[37%]为女性）。生理盐水组有1名参与者在7天前退出并被排除，平衡晶体溶液组404名参与者和生理盐水组403名参与者纳入主要分析。平衡晶体溶液组404名参与者中有121名（30%）发生DGF，生理盐水组403名参与者中有160名（40%）发生DGF（校正相对风险0.74[95%CI 0.66至0.84；p<0.0001]；校正风险差10.1%[95%CI 3.5至16.6]）。在安全性分析中，两组研究者报告的严重不良事件数量相似，平衡晶体溶液组406名参与者中有3名（<1%）报告，生理盐水组409名参与者中有5名（1%）报告（校正风险差-0.5%，95%CI -1.8至0.9；p = 0.48）。
在接受尸体供肾移植患者中，与生理盐水相比，静脉输注平衡晶体溶液可降低DGF的发生率。平衡晶体溶液应作为尸体供肾移植中静脉输液治疗的标准治疗方案。
医学研究未来基金、澳大利亚国家卫生与医学研究委员会、新西兰卫生研究委员会、澳大利亚皇家内科医师学院和百特公司。
