Questions about the BEST-Fluids trial
Authors: Christophe Masset, Agnès Chapelet, Romain Dumont, Simon Ville, Claire Garandeau, Aurélie Houzet, Delphine Kervella, Jacques Dantal, Gilles Blancho, Diego Cantarovich, Magali Giral, Lucile Figueres
Journal: The Lancet (2024)

In The Lancet, Michael G Collins and colleagues presented the results of a multicentre, randomised, clinical trial showing the benefit of a balanced crystalloid solution versus a saline solution in relation to delayed graft function (DGF) occurrence in deceased donor kidney transplantation.1Collins MG Fahim MA Pascoe EM et al.Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.Lancet. 2023; 402: 105-117Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar Although we assume these findings are of importance, we were somewhat surprised by the high rate of DGF observed in both groups (ie, 40% for the control saline solution group and 30% for the balanced solution group), which does not align with global trend. According to a 2019 report from the US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients, a 30% rate of DGF is usual among recipients of kidneys,2Hart A Lentine KL Smith JM et al.OPTN/SRTR 2019 annual data report: kidney.Am J Transplant. 2021; 21: 21-137Summary Full Text Full Text PDF PubMed Scopus (261) Google Scholar with a cold ischaemia time of more than 16 h in a majority of patients. A study from the French multicentre DIVAT cohort, which used the same definition of DGF,3Debout A Foucher Y Trébern-Launay K et al.Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation.Kidney Int. 2015; 87: 343-349Summary Full Text Full Text PDF PubMed Scopus (269) Google Scholar reported a 20% DGF rate in recipients of kidneys with less than 16 h of cold ischaemia time. In the BEST-Fluids trial, the average cold ischemia time was 10 h, which is relatively low, making the observed 30–40% DGF rate quite unexpected. As acknowledged by the authors, the widespread absence of machine perfusion use in expanded criteria donors might have affected the DGF rate in their trial. Indeed, a randomised trial conducted in Europe comparing static cold storage and machine perfusion reported DGF rates of 26·5% and 20·8%, respectively.4Moers C Smits JM Maathuis MH et al.Machine perfusion or cold storage in deceased-donor kidney transplantation.N Engl J Med. 2009; 360: 7-19Crossref PubMed Scopus (824) Google Scholar These results conduced to a wide use of machine perfusion by transplant teams, even if we assume that its usage might not be available for all patients. The statistical significance of the primary endpoint of the BEST-Fluids trial is driven by the donation after circulatory death (DCD) subgroup, which represents only 25% of the total study population. Further information on these donations would have been useful, as the donor organ's recovery could largely influence post-transplantation outcomes. Indeed, the use of normothermic regional perfusion in DCD populations was shown to be beneficial in the prevention of DGF occurrence, which was less than 20% in this at-risk population.5Savoye E Legeai C Branchereau J et al.Optimal donation of kidney transplants after controlled circulatory death.Am J Transplant. 2021; 21: 2424-2436Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar The fluid choice during a donor's resuscitation could also affect the recovery of kidney allograft function. Additionally, several papers have highlighted the potential effect of induction therapy on DGF occurrence. Early T-cell depletion, when administered intraoperatively, might reduce leukocyte sequestration in the allograft.6Chapal M Le Borgne F Legendre C et al.A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors.Kidney Int. 2014; 86: 1130-1139Summary Full Text Full Text PDF PubMed Scopus (80) Google Scholar The use of anti-IL-2 receptor antibodies in nearly 90% of the BEST-Fluids trial's participants could have contributed to the unexpected DGF rate (especially in DCD donors), although there are discrepancies on this specific subject. Finally, interpreting DGF occurrence in pre-emptive patients (2%) and in patients with peritoneal dialysis (30%) could be difficult, even if their balanced repartition probably did not influence comparison between groups. Nevertheless, despite these concerns, we believe that the issues we have raised should not discount the use of balanced crystalloids in kidney transplantation. As shown in the BEST-Fluids trial, their use was completely safe and contributed to an improved electrolytic profile in the postoperative period. Other studies have reported a reduced incidence of hyperkalaemia despite potassium supplementation due to a decreased occurrence of metabolic acidosis.7Wagener G Bezinover D Wang C et al.Fluid management during kidney transplantation: a consensus statement of the Committee on Transplant Anesthesia of the American Society of Anesthesiologists.Transplantation. 2021; 105: 1677-1684Crossref PubMed Scopus (21) Google Scholar Importantly, no differences were observed in graft function, rejection rates, or graft failure between groups in the study by Collins and colleagues. To conclude, if the results support the use of balanced crystalloid solutions during surgery and in the early postoperative period following kidney transplantation, further research is needed to explore their potential benefits in preventing DGF, particularly when considering current organ recovery strategies, such as machine perfusion. To further reduce the occurrence of DGF, which is a multifactorial condition, additional efforts should be made, including minimising ischaemic time, expanding the use of machine perfusion, optimising immunosuppression protocols, and exploring targeted treatments for donors and organs, such as the use of complement inhibitors. We declare no competing interests. Members of the Nantes DIVAT Consortium are listed in the appendix. Download .pdf (.13 MB) Help with pdf files Supplementary appendix Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trialAmong 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. Full-Text PDF Questions about the BEST-Fluids trial – Authors' replyWe thank Emmanuel Canet and Lara Zafrani, Charles Verney and colleagues, Christophe Masset and colleagues, and Gildas Gueret and Marc Laffon for their interest and comments on our Article.1 The Better Evidence for Selecting Transplant Fluids (BEST-Fluids) trial found that intravenous fluid therapy with a balanced crystalloid solution (Plasma-Lyte 148), compared with saline, reduced the incidence of delayed graft function (DGF) after deceased donor kidney transplantation. Full-Text PDF