Perioperative intravenous fluid therapy with balanced crystalloid solution reduces delayed graft function (DGF) risk compared with standard saline solution in patients undergoing deceased donor kidney transplantation, a new study finds.

“Saline (0.9% sodium chloride) is the most commonly used fluid in clinical practice but due to its supraphysiological chloride concentration (154 mmol/L), might cause hyperchloraemic metabolic acidosis, which can lead to reduced kidney perfusion and acute kidney injury,” Michael Collins, MBBS, PhD, of Royal Adelaide Hospital in Adelaide, Australia, and colleagues suggested in the Lancet.

In the double-blind Better Evidence for Selecting Transplant Fluids trial (BEST-Fluids, ClinicalTrials.gov, NCT03829488), the investigators randomly assigned 808 adults and children undergoing deceased-donor kidney transplantation at 16 hospitals to receive perioperative intravenous infusions of balanced crystalloid (Plasma-Lyte 148) or saline solution. Clinicians guided the rate and volume of fluid each patient received.

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DGF, defined as dialysis within the first 7 days of transplantation, occurred in 30% of the balanced crystalloid group compared with 40% of the saline group. Dialysis treatments were similar among patients with DGF. The risk for DGF was a significant 26% lower with use of balanced crystalloid, Dr Collins’ team reported. These results were consistent in subgroup analyses, including recipients of kidneys from donors after brain death or circulatory death, kidney donor risk index, and ischemic times.

At 1 year, graft function and graft failure rates also did not differ significantly between groups, the investigators reported.

Study investigators estimated that 1 case of delayed graft function would be prevented for every 10 patients treated with balanced crystalloid solution.

While lower in sodium, balanced crystalloids contain potassium (4-5 mmol/L) prompting concerns about hyperkalemia. Hyperkalemia within 2 days after transplantation, however, occurred in similar proportions of the balanced crystalloid and saline groups: 56% vs 57%. Significantly fewer patients in the balanced crystalloid group were admitted to intensive care units for continuous ventilatory support than in the saline group: less than 1% vs 3%. Serious adverse events rates were comparable between groups: less than 1% vs 1%, respectively.

“Because of the substantial morbidity and costs associated with DGF and subsequent need for dialysis, our finding of a substantial benefit for balanced crystalloid solution over saline without any concerning signals for harm provides a strong justification for a change to clinical practice,” Dr Collins and colleagues wrote.

In an accompanying editorial, Adnan Sharif, MD, PhD, of University Hospitals Birmingham in Birmingham, United Kingdom, agreed:

“The results from BEST-Fluids can be adopted by the international transplant community for attenuation of DGF risk after kidney transplantation, with evidence supporting the use of balanced crystalloid solutions as the standard of care for intravenous fluid replacement therapy before and after transplantation.”

Dr Sharif pointed out that further studies are needed to determine if the reduction in DGF is driven by the use or avoidance of 0.9% sodium chloride. He also pointed out that static cold storage was the predominant method of kidney preservation in this study. Whether the same reduction in DGF would be observed with deceased donor kidneys preserved via hypothermic machine perfusion or novel preservation technologies such as normothermic machine perfusion remains to be seen.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References

Collins 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. Published online June 18, 2023. doi:10.1016/S0140-6736(23)00642-6

Sharif A. Choosing fluids to reduce the risk of delayed graft function after deceased donor kidney transplantation. Lancet. Published online June 18, 2023. doi: 10.1016/S0140-6736(23)00770-5