Balanced Crystalloid Solution Versus Saline in Deceased Donor Kidney Transplantation (BEST-Fluids)

Summary by Morgan Keegan, MD 11.29.23
https://www.thelancet.com/article/S0140-6736(23)00642-6/fulltext

Clinical Hypothesis: Intraoperative use of the balanced crystalloid solution, Plasmalyte, would lead to a lower incidence of delayed graft function following deceased donor kidney transplantation compared to the use of normal saline. 

Take Home Message:

· Administration of balanced crystalloid solution leads to a lower incidence of delayed graft function following deceased donor kidney transplantation compared to normal saline.

· There were no observed differences in the incidence of hyperkalemia or volume overload, length of hospitalization, graft survival, or mortality between patients who received balanced crystalloid versus normal saline.

Summary:

Background: 30-50% of patients who undergo deceased donor kidney transplantation are at risk of delayed graft function (DGF), as defined as a need for dialysis within 7 days following transplantation. DGF is thought to occur due to ischemia-reperfusion injury. Intravenous fluids are administered to maintain graft perfusion for optimal graft function. Normal saline is the most commonly used fluid in kidney transplantation, however, large volumes may lead to hyperchloremic metabolic acidosis which contributes to reduced kidney perfusion and kidney injury. In 2021, a meta-analysis demonstrated lower risks of acidosis and hyperkalemia with the use of balanced solutions compared to normal saline, though with uncertain evidence on the risk of DGF. This study compared the use of Plasmalyte and 0.9% sodium chloride solutions in patients undergoing deceased donor kidney transplantation to determine if balanced solutions reduce the risk of DGF. 

Study Design: double-blinded randomized controlled trial

Methods: Patients were randomized to receive Plasma-Lyte or 0.9% Sodium Chloride for maintenance, replacement, and resuscitation intraoperatively and postoperatively until 48h after transplant or cessation of IV fluids (whichever occurred first). Clinicians involved in the patients’ care made decisions regarding the rate and volume of administration as well as when to discontinue administration. 807 patients were included in the intention-to-treat analysis, with 404 in the Plasmalyte group and 403 in the normal saline group.

Inclusion criteria: any age patient admitted for deceased donor kidney transplantation across 16 hospitals in Australia and New Zealand

Exclusion criteria: multi-organ transplantation, weight < 20kg in pediatric patient, if physician deemed the patient too small for a blind fluid study

Primary outcome: incidence of delayed graft function as defined by the need for dialysis within 7d of transplantation

*note: primary outcome in the original version of the trial was a composite of the duration of DGF in days in those requiring dialysis and creatinine reduction ratio of POD#2 (served as a measurement of graft function recovery) in those not requiring dialysis. The primary outcome was changed due to concern that this outcome would be challenging to interpret and would not change clinical practice. 

Secondary outcomes: number of dialysis treatments to day 28, a composite of DGF duration and creatinine reduction ratio on day 2, creatinine reduction ratio on day 2 and creatinine reduction of 10% or more in the first 3 days, post-transplant hyperkalemia (K > 5.5mmol), treatment required for hyperkalemia and peak potassium, fluid overload (>5% weight gain by POD#2), urine output to POD#2, use of inotropes or vasopressors during and after surgery, acute rejection, the incidence of kidney biopsy performed, mortality, graft survival, graft function (eGFR), duration of hospitalization 

Results: Delayed graft function occurred in 121 of 404 participants (30%) of the balanced crystalloid and 160 of 403 participants (40%) in the normal saline group with a relative risk of 0.74 (P<0.0001) with effect modification noted when comparing donor type where a greater effect was seen in recipients of a kidney after circulatory death compared to after brain death. The most common indications for dialysis were hypervolemia, uremia, and hyperkalemia. In a subgroup analysis of the participants requiring dialysis, there were no differences in the number of sessions to day 28 or the total duration of dialysis between the two groups. 

Mean fluid volume was higher in the balanced crystalloid group (8143mL vs 7180mL).

There was increased mean urine output during the first 48 hours following transplantation in the balanced crystalloid group compared to the normal saline group (6011mL vs 4948mL).

No other significant differences were observed in the secondary outcomes between the groups. 

Adverse events were similar in the two groups, except fewer participants were admitted to the ICU for ventilatory support in the balanced group. 

Discussion/conclusion:

The use of balanced crystalloid solution for maintenance and fluid resuscitation in the intraoperative and postoperative period leads to a lower incidence of delayed graft function following deceased donor kidney transplantation compared to normal saline without observed differences in the incidence of hyperkalemia or volume overload, length of hospitalization, graft function at 1y, graft survival or mortality between patients who received balanced crystalloid versus normal saline. Adverse outcomes were similar in both groups, however, more patients who received normal saline were admitted to intensive care units. The reduced incidence of DGF in the balanced crystalloid group is hypothesized to be due to the avoidance of hyperchloremic metabolic acidosis, thereby decreasing renal vasoconstriction and ultimately reducing ischemia to the grafted organ. This study was not powered to detect differences in graft function at 1y or mortality, and observational analyses have shown differences in graft function in patients who receive balanced crystalloid vs normal saline are not evident until 3y post-transplantation. Therefore, larger and longer-term studies are necessary to investigate differences in mortality and long-term graft function.