Dr Michael G. Collins

ORLANDO, Florida — Using a low-chloride, balanced crystalloid solution for all intravenous (IV) fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.

“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” said Michael G. Collins, MBChB, PhD, at Kidney Week 2022, organized by the American Society of Nephrology.

“Balanced crystalloids are cheap, readily available worldwide, and this simple change in kidney transplant practice can easily be implemented in global practice…almost immediately,” said Collins, a nephrologist at Royal Adelaide Hospital, Australia.

A 1-L bag of balanced crystalloid fluid is more expensive; however, it has a US retail cost of about $2-$5 per bag compared with about $1 per bag of saline fluid, Collins added.

Various other commentators had mixed views. Some agreed with Collins and said the switch could be made immediately, although one researcher wanted to see more trials. Another wondered why balanced crystalloid fluid hadn’t seemed to provide benefit in studies in acute kidney injury.

Treating 10 Patients Prevents One Delayed Graft Function

The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Collins reported.

This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.

Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30% to 50% of people who received these organs, Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days as well as increased risk for long-term graft failure and death.

A secondary outcome — the number of dialysis sessions required during the 28 days following transplantation — was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.

Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation compared with controls.

Chloride Is the Culprit

Dr Karen A. Griffin

“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Collins. Specifically, he cited the chloride content of saline — which contains 0.9% sodium chloride — as the culprit by causing reduced kidney perfusion.

“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center in Hines, Illinois. But Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.

However, Pascale H. Lane, MD, a pediatric nephrologist with Oklahoma University Health in Oklahoma City, predicted that based on these results, “I think it will be rapidly embraced” by US clinicians. Lane expressed concern about the availability of an adequate supply of balanced crystalloid fluid, but Collins said he did not believe supply would be an issue based on current availability.  

This was “a beautiful study, very well done, with nice results, and a very easy switch to balanced crystalloid fluids without harm,” commented Richard Lafayette, MD, a nephrologist and professor of medicine at Stanford University, California.

Success Attributed to Early Treatment

Dr Pascale H. Lane

But Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the intensive care unit (ICU)?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.

Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.   

The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.

Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.

During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.

The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.

BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Collins, Griffin, and Lane have reported no relevant financial relationships. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera, and has been an advisor to Akahest and Equillium.

Kidney Week 2022. Abstract FR-OR61. Presented November 4, 2022.

Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler

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