What’s the best solution to use during kidney transplantation?
Myron Yaster MD and Jayant K. Deshpande MD
I’ve always joked that there is nothing NORMAL about normal (0.9%) saline…it really should be called Abnormal saline because it simply has way too much chloride (154 mmol/L). This high chloride concentration may cause a hyperchloremic acidosis which can lead to reduced kidney perfusion and acute kidney injury. In today’s PAAD, Collins et al.1 hypothesized that using a balanced, more physiologic, low chloride salt solution (Plasma-Lyte 148), a solution that more closely approximates human plasma instead of normal saline, would reduce the incidence of delayed graft function in children and adults receiving deceased donor kidney transplantation. The results of this study have enormous implications in perioperative fluid management in this patient population and perhaps in all of our patients. Indeed, isn’t it time we retire (ab)normal saline and switch to a balanced solution in all of our patients? Myron Yaster MD
PS: Jay and I will revisit this issue over the next few days with another article on the same topic by another investigator group. Stay tuned!
Original article
Collins MG, Fahim MA, Pascoe EM, Hawley CM, Johnson DW, Varghese J, Hickey LE, Clayton PA, Dansie KB, McConnochie RC, Vergara LA, Kiriwandeniya C, Reidlinger D, Mount PF, Weinberg L, McArthur CJ, Coates PT, Endre ZH, Goodman D, Howard K, Howell M, Jamboti JS, Kanellis J, Laurence JM, Lim WH, McTaggart SJ, O'Connell PJ, Pilmore HL, Wong G, Chadban SJ; BEST-Fluids Investigators; Australasian Kidney Trials Network. Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2023 Jul 8;402(10396):105-117. doi: 10.1016/S0140-6736(23)00642-6. Epub 2023 Jun 18. Erratum in: Lancet. 2023 Jul 1;402(10395):26. PMID: 37343576.
“Patients who receive a kidney transplant from a deceased donor are at risk of delayed graft function (DGF), defined as the requirement for dialysis within the first week after transplantation due to poor kidney function.2 DGF occurs as a consequence of ischaemia-reperfusion injury of the transplanted kidney and affects 30–50% of recipients or more.2 DGF is associated with inferior outcomes, including increased health-care costs, driven primarily by requirement for dialysis and prolongation of hospital stay, and increased risks of acute rejection, graft failure, and death3.”1
Balanced crystalloids have been associated with a lower risk of DGF compared with saline in observational studies even though they contain potassium which could exacerbate preexisting hyperkalemia. Today’s PAAD was “a pragamatic, investigator-initiated, registry-based, double-blind, randomised, controlled trial conducted at 16 hospitals in Australia (12 sites) and New Zealand (four sites).”1 The volume and rate of fluid administration and when to stop fluid administration was determined by the treating clinical physicians. As a review: Plasma-Lyte 148 used in this trial consisted of an isotonic buffered crystalloid solution containing sodium (140 mmol/L), potassium (5 mmol/L), magnesium (1·5 mmol/L), chloride (98 mmol/L), acetate (27 mmol/L), and gluconate (23 mmol/L) in sterile water, balanced to a pH of 7·4. Normal saline consists of a solution of 154 mmol/L of sodium and 154 mmol/L of chloride in sterile water.
OK, what did they find? “A total of 808 participants (404 in the balanced crystalloid group and 404 in the saline group) were enrolled in the trial.”1 Compared with the saline group, the balanced crystalloid group had lower mean serum chloride and sodium concentrations and higher mean serum bicarbonate concentrations and blood pH from transplantation to postoperative day 2. Mean serum concentrations of potassium, urea, and haemoglobin did not differ between the groups. Mean serum creatinine concentrations measured up to day 7 were similar in both groups”1
“The primary outcome of DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group and 160 (40%) of 403 participants in the saline group (adjusted relative risk [RR] 0·74, 95% CI 0·66–0·84; p<0·0001),”1 The authors conclude; “Patients receiving a kidney transplant from a deceased donor are at lower risk of delayed graft function if they receive intravenous fluid therapy with balanced crystalloid solution rather than saline, with approximately one case of DGF prevented for every ten patients treated. Use of balanced crystalloids does not increase the risk of serious adverse events or hyperkalaemia. The available evidence suggests that balanced crystalloid solution should be the standard of care intravenous fluid in deceased donor kidney transplantation.”1
Isn’t it time we retire (ab)normal saline and switch to a balanced solution for our default perioperative IV fluid in all of our patients and not just for cadaveric kidney transplant patients? We think this study and conclusions should make us all rethink which fluid we administer perioperatively in all of our patients. Clearly, we should be using PlasmaLyte in cadaveric kidney transplants. But, why do we continue to use (ab)normal saline and ringers lactate in any of our patients? Why not simply administer PlasmaLyte to everyone. We have no idea what the cost differences are between these various solutions, but surely stocking a single fluid instead of multiple different solutions may make cost differences irrelevant. What do you think? Send your responses to Myron who will post in a Friday reader response.
References
1. 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 (London, England) 2023;402(10396):105-117. (In eng). DOI: 10.1016/s0140-6736(23)00642-6.
2. Mallon DH, Summers DM, Bradley JA, Pettigrew GJ. Defining delayed graft function after renal transplantation: simplest is best. Transplantation 2013;96(10):885-9. (In eng). DOI: 10.1097/TP.0b013e3182a19348.
3. Butala NM, Reese PP, Doshi MD, Parikh CR. Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis. Transplantation 2013;95(8):1008-14. (In eng). DOI: 10.1097/TP.0b013e3182855544.