APM Anesthesia and Pain MedicineAnesth Pain Med 1975-5171 2383-7977 Korean Society of Anesthesiologists 10.17085/apm.24180 apm-24180 Review Selection of intraoperative fluid for kidney transplantation Fluid management during kidney transplantation http://orcid.org/0000-0002-7069-6264 LeeJeong Eun http://orcid.org/0000-0003-2488-5221 JungHoon Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea Corresponding author: Hoon Jung, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea Tel: 82-53-200-3867 Fax: 82-53-426-3868 E-mail: wing2392@naver.com 31 1 2025 25 1 2025 20 1 14 22 9 12 2024 12 1 2025 13 1 2025 © The Korean Society of Anesthesiologists, 2025 2025 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The kidney, the most frequently transplanted organ, represents the optimal treatment for end-stage renal disease. Transplanted kidneys are highly vulnerable to perioperative injuries such as hypotension and hypovolemia, which can be influenced by perioperative fluid management. Postoperatively, delayed graft function increases the risk of graft failure. Although adequate volume administration can reduce delayed graft function, the type of intraoperative fluid most likely to benefit and support graft function remains unclear. Traditionally, crystalloids have been the primary choice for fluid management during kidney transplantation. Among these, 0.9% sodium chloride is the most commonly used, as its potassium-free composition minimizes the risk of hyperkalemia in patients with end-stage renal disease. Albumin is not routinely used, whereas synthetic colloids are discouraged owing to their nephrotoxicity. To date, 0.9% sodium chloride has demonstrated fewer advantages compared with balanced crystalloids, particularly regarding acid-base homeostasis, electrolyte balance, and delayed graft function. This review aims to examine the existing evidence on the effect of crystalloids and colloids on postoperative graft function and to recommend an appropriate fluid regimen, including balanced crystalloids, for kidney transplantation.

 Albumins Crystalloid solutions Delayed graft function Fluid therapy Kidney transplantation Perioperative fluid management INTRODUCTION

Kidney transplantation (KT) has been a viable treatment for end-stage renal disease since the first successful procedure in 1954 [1]. Advances in immunosuppressive therapies and the persistent shortage of donor organ have necessitated the inclusion of expanded criteria donors [2]. The varying functional statuses or ischemic phase characteristics of donor organs are associated with delayed graft function, which is defined as the requirement for dialysis within seven days post-transplantation. Additionally, the impact of delayed graft function is closely related to the short- and long-term outcomes of KT [3,4].

The factors influencing delayed graft function in KT are complex and infinite. Although the risk factors for graft failure are not yet fully controlled, intraoperative fluid management plays a crucial role in maintaining acid-base homeostasis and optimal intravascular volume, aspects that anesthesiologists can directly influence during surgery [4]. The effects of 0.9% sodium chloride (saline), traditionally the most commonly used fluid, and the balanced solution on delayed graft function have been extensively studied. However, the clinical effect of crystalloid selection on delayed graft function and the incidence of graft failure remains inconclusive. Recent reviews by the American Society of Anesthesiologists and Cochrane library have emphasized the importance of cautious intraoperative fluid selection, particularly in cases of acidosis or hyperkalemia [5,6].

Despite the absence of a standardized protocol for fluid management, this review aims to propose a more favorable fluid type, taking into account its impact on the incidence of delayed graft function in KT.

 CRYSTALLOIDS

The primary goal of fluid management during KT is to maintain graft perfusion by administering an appropriate amount of crystalloids while avoiding synthetic colloids or vasoconstrictors, which could induce renal vasoconstriction and subsequent acute kidney injury [7]. A multicenter analysis of KT in the US revealed that 83% of hospitals used saline as the primary crystalloid, with > 90% of recipients receiving saline [8].

Crystalloids are broadly classified into balanced and unbalanced solutions, with saline being an unbalanced crystalloid (Table 1). Over the past two decades, a substantial number of studies have demonstrated an association between continuous saline administration and acute kidney injury in various patient populations. Chowdhury et al. [9] first demonstrated a reduction in the renal artery blood flow velocity, assessed via magnetic resonance imaging, by up to 13% following the infusion of 2 L of saline over 1 h in healthy male volunteers. The Saline Against Lactated Ringer’s or Plasmalyte in the Emergency Department trial, which included noncritically ill adults, reported a higher incidence of adverse kidney injury within 1 month in the saline group than in the balanced crystalloids group (5.6% vs. 4.7%, P = 0.01) [10]. Similarly, the Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit trial reported a 1.1% lower incidence of major adverse kidney events in patients receiving balanced crystalloids compared with saline (14.3% vs. 15.4%; P = 0.04) [11]. In contrast, the Saline or Lactated Ringer’s (SOLAR) trial, conducted in patients undergoing elective non-KT surgeries, found no effect of fluid type on acute kidney injury [12]. The notable differences in SOLAR trial were the surgical patient's physical status and the volume of intraoperatively administered fluid. The SOLAR trial focused on patients undergoing elective colorectal or orthopedic surgery, all of whom had a relatively stable physical condition, and excluded those undergoing urgent or emergent surgeries. Additionally, when compared with the fluid management in the emergency department or intensive care unit, the median fluid volume administered over a short period of 2 to 4 h was approximately 2 L; therefore, differences in the volume of fluid administered and the duration of infusion should also be considered.

0.9% sodium chloride (saline) 1. Hyperchloremic acidosis

Normal saline, commonly referred to as saline, is considered an abnormal fluid. It consists of 154 mmol/L of sodium and chloride in equal concentration, without potassium. The chloride concentration in saline is higher than that found in the human serum (98–107 mmol/L), making it non-physiological. Plasma chloride is a crucial electrolyte, as it is the main anion of extracellular fluid and plays a critical role in maintaining the acid-base balance of the extracellular fluid [13].

Administering a substantial amount of saline alone can lead to metabolic acidosis, primarily recognized as dilutional acidosis, due to decreased bicarbonate levels and extracellular volume expansion [14]. In contrast, the Stewart acid-base balance approach suggests that hyperchloremia, resulting from saline administration, is responsible for metabolic acidosis. This approach accurately quantifies hyperchloremic metabolic acidosis [15-17]. pH is determined by the strong ion difference, defined as the difference between strong cation (Na+ + K+) and strong anion (Cl- + lactate-). After administering intravenous saline, equal concentrations of sodium and chloride are introduced in the serum, with the accumulation of chloride occurring at a much higher rate. Consequently, the strong ion difference decreases, leading to hyperchloremic metabolic acidosis. In gynecological surgery, hyperchloremic acidosis occurs in a dose-dependent manner following the infusion of 30 ml/kg of 0.9% saline within 2 h of surgery [18]. Furthermore, intraoperative fluid management in KT necessitates the infusion of large volumes of intravascular crystalloids to maintain graft perfusion [19]. The required intraoperative fluid volume for KT ranges from approximately 2.5 to 6 L of crystalloids over 2–5 h, and this amount of saline infusion inevitably leads to hyperchloremic metabolic acidosis [20-22].

Saline-induced hyperchloremic metabolic acidosis can potentiate intraoperative electrolyte imbalance in recipients with end-stage renal disease and in grafts with ischemic reperfusion injury. Additionally, severe metabolic acidosis can lead to significant inflammation, vasodilatory hypotension, and coagulopathy [23-25].

 2. Hyperchloremia

Similar to its impact on plasma acid-base balance, saline-induced hyperchloremia can directly affect renal hemodynamics (Table 2). Wilcox et al. [26] demonstrated in an animal study that plasma chloride-regulated renal vascular resistance and hyperchloremia resulted in decreased glomerular filtration. Even in healthy individuals, saline has consistent effects on kidney functions, including delayed first urination, increased antidiuretic hormone secretion, and decreased natriuresis [27,28]. The mechanism by which hyperchloremia causes acute kidney injury in critically ill patients aligns with findings from animal studies. When chloride concentration increases in the distal tubule, tubuloglomerular feedback is activated, leading to afferent arteriole vasoconstriction. This, in turn, reduces glomerular blood flow, decreases the glomerular filtration rate, and contributes to acute kidney injury [16,29].

Nevertheless, the clinical impact of intraoperative saline-induced hyperchloremia or hyperchloremic acidosis on delayed graft function still remains inconclusive. In a retrospective observational study of deceased donor KT using saline, 11% of cases developed hyperchloremia or hyperchloremic metabolic acidosis, whereas the incidence of delayed graft function was 20% [30]. The incidence of hyperchloremia or hyperchloremic acidosis was comparable regardless of whether delayed graft function developed. The delayed graft function group received more saline volume in the operating room and intensive care unit than the non-delayed group (5,240 L vs. 4,732 L, P = 0.03), although intraoperative fluid volume was not different between the groups (2,397 L vs. 2,058 L, P = 0.19). In patients who developed delayed graft function, donor terminal creatinine levels were significantly lower, and cold ischemic time was significantly longer. Additionally, in major abdominal surgery, the amount of intraoperative fluid administered was observed to follow a U-shaped distribution, which resulted in postoperative kidney injury [31]. Hence, these results were interpreted as a decrease in glomerular filtration rate due to kidney congestion caused by the large volume of fluid, rather than acute kidney injury resulting from saline-related hyperchloremia. Consistent results regarding the effect of saline chloride on transplanted kidneys have yet to be established. Therefore, further studies, particularly those investigating the effect of saline on delayed graft function, are needed.

 3. Hyperkalemia

Hyperkalemia is a common occurrence during KT surgery and may even require postoperative renal replacement therapy. Saline was previously considered as the only option to prevent hyperkalemia; however, it can also contribute to hyperkalemia owing to saline-induced metabolic acidosis [8,20]. In hyperchloremic metabolic acidosis, hydrogen ions enter cells as a compensatory mechanism, simultaneously causing the release of potassium into the extracellular space. Potassium is the major cellular cation, accounting for only 2% of the total potassium present in the extracellular space. Therefore, even a small shift of potassium from the intracellular to the extracellular space can lead to hyperkalemia, which not only impairs cardiovascular stability but also increases the risk of cardiac arrhythmia [32].

Weinberg et al. [21] reported that administration of saline in deceased donor KT resulted in a higher incidence of hyperkalemia compared with Plasmalyte (80% vs. 50%, P = 0.037). The peak serum potassium concentration was 6.1 mmol/L after saline administration, compared with 5.4 mmol/L following Plasmalyte infusion (P = 0.009). Furthermore, chloride concentration was significantly higher in the saline group.

 Balanced crystalloids

Balanced crystalloids contain sodium and chloride at slightly lower concentrations than saline, more closely resembling human plasma. Balanced crystalloids are primarily used in Ringer’s lactate and Plasmalyte. They also include potassium, calcium, and buffers (gluconate, acetate, and lactate). Ringer’s lactate contains 4 mmol/L potassium, and Plasmalyte contains 5 mmol/L potassium. Balanced crystalloids have not been associated with hyperkalemia even after the administration of large volumes during KT [20,22]. Additionally, the infusion of balanced crystalloids is associated with a lower incidence of hyperchloremia and metabolic acidosis, owing to lower chloride concentrations and buffers, compared with saline [20,22].

Nevertheless, Ringer’s lactate is a moderately hypo-osmolar solution with an electrolyte composition that differs from human plasma. Certain issues may still arise when large amounts of Ringer’s lactate are injected. Large volumes of Ringer’s lactate may cause metabolic alkalosis, with a marked increase in lactate levels [22]. Lactate is also converted to glucose. Despite no differences in blood sugar changes during surgery, perioperative glucose levels should be monitored when large amounts of Ringer’s lactate are administered. In particular, avoiding Ringer’s lactate in patients with diabetes taking metformin is safe because lactate metabolism may be delayed in these patients [33]. Another adverse effect of administering large volumes of Ringer’s lactate is related to the central nervous system. In recipients with end-stage renal disease, uremia may affect the blood-brain barrier, and the administered hypo-osmolar Ringer’s lactate may increase its permeability, potentially leading to cerebral edema [34,35].

Plasmalyte has an electrolyte composition that is closest to that of plasma among crystalloids. The acetate and gluconate present in Plasmalyte act as bicarbonate precursors, which can help attenuate acidosis [14]. Theoretically, Plasmalyte should offer a superior electrolyte balance; however, clinical studies have shown no differences in pH, bicarbonate, potassium, and chloride levels when compared with Ringer’s lactate [22,36]. Since the effect of balanced crystalloids on KT has been investigated mostly in comparison with saline, further studies are required to identify a more beneficial fluid for KT among balanced crystalloids.

 Saline vs. balanced crystalloids in KT

Over the past few decades, numerous studies have compared saline and balanced crystalloids in KT surgery (Table 3). However, the donors’ conditions are inconsistent, as the studies include both living and deceased donors. Furthermore, the methods for evaluating delayed graft function and the timing of measurement are diverse.

In 2016, a Cochrane [5] review analyzed six studies (477 patients with KT) that compared saline and balanced crystalloids. The authors reported a higher prevalence of hyperchloremic acidosis in patients receiving saline infusions. However, no significant differences were observed in the potassium concentration or delayed graft function. The reviewed studies indicated that the majority of participants had living donors.

Although studies on brain-dead organs, which typically have a relatively longer cold ischemic time, have been lacking, the 2023 BEST-Fluids study [37], a multicenter randomized controlled trial, investigated 808 deceased donor KT patients. The results showed that Plasmalyte significantly lowered the incidence of delayed graft function compared with saline, with higher postoperative urine output, lower serum chloride, and higher levels of bicarbonate and pH. Additionally, the incidence of hyperkalemia in Plasmalyte was comparable to that in saline. However, no differences in serum creatinine levels, graft failure, or mortality were detected between the balanced Plasmalyte and saline groups.

As balanced crystalloids evolve to have a composition closer to that of plasma, fluid therapy is gradually shifting from the routine use of saline to low-chloride-balanced crystalloids. Saline is still widely used in KT owing to the absence of a single established fluid regimen. Patients with KT often have an acid-base imbalance due to renal failure and are vulnerable to metabolic acidosis from the massive fluid therapy. Moreover, normalization of hyperchloremic acidosis is difficult because there is no established regimen for postoperative treatment [38]. A Consensus Statement of the Committee on Transplant Anesthesia of the American Society of Anesthesiologists addressed the favorable metabolic profiles with balanced crystalloid administration [6]. Therefore, despite concerns about hyperkalemia, balanced crystalloids can be recommended because they maintain the acid-base balance and prevent hyperkalemia through their alkalizing properties, even though they contain potassium.

 COLLOIDS

A large intravascular volume of crystalloids is required to maintain blood flow in a transplanted kidney. However, crystalloids remain in the intravascular space for only approximately 20% of the volume, and their plasma half-life is only approximately 30 min [45]. Additionally, increased microvascular permeability in an ischemic kidney affects renal perfusion. In the case of crystalloids, maintaining plasma volume expansion at a level that can increase tissue perfusion is burdensome and difficult. In cases of severe intravascular volume deficits, colloids may be considered volume expanders along with crystalloids; however, the routine use of colloids is not recommended in KT [46].

Albumin

Albumin is a natural colloid that does not cause renal tissue accumulation or damage unless injected in excessive amounts. However, studies on the effects of albumin on KT are limited. Albumin administration can help move interstitial fluid into the intravascular space, thereby preventing hypovolemia and reducing tissue edema [47,48]. In studies of deceased donor KT, early graft function was higher when albumin was used alongside crystalloids compared with crystalloids alone [49,50]. In contrast, studies involving living donors have shown no difference in the total amount of goal-directed crystalloids infused when albumin was used. Furthermore, these studies demonstrated no differences in the improved outcomes related to total urine output, serum creatinine, and tissue and pulmonary edema [51,52].

In addition to increasing plasma oncotic pressure, albumin exerts nephroprotective effects in critically ill patients by scavenging reactive oxygen species, antioxidant activity, enhancing protein transport, anti-inflammatory properties, and buffering acid-base capacity [53-55]. In a meta-analysis on acute kidney injury development, serum albumin reduction was shown to be an independent risk factor of acute kidney injury [56].

The disadvantages of albumin include its high cost, the risk of allergic reactions, and the potential for infection, which are rare. Additionally, excessive serum albumin poses the risks of decreased glomerular filtration rate, poor tissue perfusion, pulmonary edema, and interstitial edema due to increased oncotic pressure [57]. Therefore, based on the clinical results to date, there is no indication for the routine use of albumin. Furthermore, albumin administration may be beneficial for kidney function in cases requiring albumin supplementation, such as hypoalbuminemia due to large amounts of crystalloid administration, provided the serum albumin level does not exceed 30 g/L [49,52,56].

 Starches

Because hydroxyethyl starch (HES) is a large molecule, its metabolism and excretion in urine are delayed. Moreover, it may accumulate in the renal tissue, causing osmotic nephrosis. Although osmotic nephrosis is typically a reversible change in the tubular structure, the vacuolar retention of HES in the ischemic kidney is prolonged, whereas its degradation is delayed, which can lead to osmotic nephrosis–related acute kidney injury, such as tubular atrophy and interstitial fibrosis [58]. In addition to nephrotoxicity, HES causes perioperative coagulopathy, e.g., decreased platelet function, factor VIII, and von Willebrand factor. Furthermore, various adverse effects, such as pruritus, anaphylactoid reaction, hepatic dysfunction, and tissue deposition in various organs and tissues, have been reported [59]. Few studies comparing low molecular–weight HES did not show any significant difference in short-term graft function [60,61]. However, evidence for the safe use of HES in KT is lacking. Given the high risk of acute renal failure following HES infusion in critically ill patients with preexisting renal diseases, routine HES use is not recommended for graft function in KT recipients [62,63].

Although the risks of perioperative HES use for optimizing KT fluid management are well-known, administering HES in preoperative critical care in brain-dead donors may also affect delayed graft function. Donors require massive fluid therapy due to polyuria and hypotension caused by diabetes insipidus, decreased sympathetic tone, and vasoplegia. In these conditions, HES is sometimes used as a volume expander in brain-dead donors. Grafts that received HES before surgery had a higher incidence of extrarenal hemodialysis in the acute postoperative phase, as well as higher serum creatinine levels, indicating a worse prognosis [64,65]. Moreover, HES was related to postoperative osmotic diuresis, cytoplasmic vacuolization, tubular swelling, and obstruction. Therefore, HES should be avoided in KT. Additionally, HES administration in brain-dead donors can be associated with delayed graft function.

 CONCLUSION

During KT, appropriate intraoperative fluids should be chosen with the aim of potentiating early graft function. Although the detrimental effects of saline on delayed graft function have not been currently fully elucidated, the risks associated with administering saline cannot be ignored. Balanced crystalloids can be considered a better option as intraoperative fluids in KT without an increased risk of hyperkalemia while ameliorating metabolic acidosis attributed to hyperchloremia. Furthermore, albumin can facilitate the maintenance of plasma colloid osmotic pressure; thus, albumin can be safely administered within the normal serum albumin level without nephrotoxicity. However, the effect of fluid type on long-term graft survival remains unknown, warranting careful observation of the related outcomes.

FUNDING

None.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

DATA AVAILABILITY STATEMENT

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

AUTHOR CONTRIBUTIONS

Conceptualization: Sang-Wook Lee, Woo-Jong Choi. Project administration: Sang-Wook Lee. Writing - original draft: Sang-Wook Lee. Writing - review & editing: Sang-Wook Lee, Woo-Jong Choi. Investigation: Sang-Wook Lee. Supervision: Sang-Wook Lee, Woo-Jong Choi.

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Composition of Crystalloids

Solution type pH Na+ Cl- K+ Ca2+ Mg2+ Lactate Acetate Gluconate Osmolarity
Unbalanced Saline 5.5 154 154 - - - - - - 308
Balanced Ringer’s Lactate 6.5 131 111 4 2 - 29 - - 273
Plasmalyte 7.4 140 98 5 - 1.5 - 27 23 295

All electrolyte concentrations are shown in mmol/L. Osmolarity is shown in mOsm/L.

Clinical Conditions Possibly Related to Intraoperative Saline Infusion

Hyperchloremia
Hyperkalemia
Metabolic acidosis
Decrease in plasma bicarbonate
Decreased glomerular filtration rate
Prolonged time to first micturition
Decreased urine output
Poor gastric mucosal perfusion
Subjective mental change

Characteristics of Crystalloids in Kidney Transplantation Studies

Reference Year Study design Country Donor Number of patients Interventions compared Primary endpoint and result
Kim et al. [39] 2013 Double-blind randomized controlled trial Korea Living 60 Saline, Plasmalyte Acid-base balance.
Plasmalyte maintained a stable acid-base balance than saline after postreperfusion period.
Potura et al. [40] 2015 Prospective randomized controlled trial Austria Deceased 150 Acetate-buffered balanced crystalloid, saline Perioperative hyperkalemia (serum potassium level > 5.9 mmol/L).
The incidence of hyperkalemia in balanced crystalloid showed no difference (ns, 17% vs. bc, 21%, P = 0.56)
Weinberg et al. [21] 2017 Prospective randomized double-blind controlled study Australia Deceased 50 Saline, Plasmalyte The incidence of hyperkalemia within 48 h of surgery.
Saline showed higher incidence of hyperkalemia than Plasmalyte (80% vs. 50%, P = 0.037)
Castro et al. [41] 2018 Retrospective cohort analysis Spain Living and deceased 94 Saline Postoperative potassium level.
The injection volume of saline was associated with an increased potassium level 24 h after admission (P = 0.026).
Nesseler et al. [30] 2020 Retrospective observational study France Deceased 359 Saline Delayed graft function.
The incidence of delayed graft function was associated with perioperative saline infusion volume.
Kolodzie et al. [42] 2021 Retrospective cohort study USA Living and deceased 2515 Saline Delayed graft function.
The volume of saline injection and the incidence of delayed graft function increased proportionally.
Saini et al. [43] 2021 Prospective, randomized, double-blind study India Living 180 Saline, Ringer’s lactate, Plasmalyte pH at the end of surgery.
Saline showed the lowest pH at the end of surgery.
Paulo et al. [44] 2022 Single-blind randomized controlled trial Brazil Deceased 104 Saline, Plasmalyte Delayed graft function.
The incidence of delayed graft function did not differ between the groups.
Medeiros et al. [36] 2023 Randomized controlled trial Brazil Living or deceased 53 Saline, Ringer’s lactate, Plasmalyte Postoperative pH and serum potassium level.
Saline showed lower pH. Potassium levels were not different between the groups.
Collins et al. [37] 2023 Multicenter Randomized controlled trial Australia, New Zealand Deceased 808 Saline, Plasmalyte Delayed graft function.
The balanced crystalloid group showed a lower incidence of delayed graft function than the saline group (30% vs. 40%; adjusted relative risk, 0.74; P < 0.0001)