Effects Of The Type Of Intraoperative Fluid in Living Donor Kidney Transplantation: A Single-Center Retrospective Cohort Study

Purpose: 

Perioperative fluid management in kidney transplant recipients is crucial to supporting the fluid, acid-base, and electrolyte balance required for graft perfusion. However, the choice of intraoperative crystalloids in kidney transplantation remains controversial. We conducted a single-center retrospective cohort study to evaluate the impact of intraoperative fluids on acid-base and electrolyte balance and graft outcomes.

Materials and Methods: We included 282 living donor kidney transplant recipients from January 2010 to December 2017. Patients were classified into two groups based on the type of intraoperative crystalloids used (157 patients in the half-saline group and 125 patients in the balanced crystalloid solutions group, Plasma-Lyte). 

Results: Compared with the half-saline group, the Plasma-lyte group showed less metabolic acidosis and hyponatremia during surgery. Hyperkalemia incidence was not significantly different between the two groups. Changes in postoperative graft function assessed by blood urea nitrogen and creatinine were significantly different between the two groups. Patients in the Plasma-lyte group exhibited consistently higher glomerular filtration rates than those in the half-saline group at 1 month and 1 year after transplantation after adjusting for demographic differences. 

Conclusion: Intraoperative Plasma-lyte can lead to more favorable results in terms of acid-base balance during kidney transplantation. Patients who received Plasma-lyte showed superior postoperative graft function at 1 month and 1 year after transplantation. Further studies are needed to evaluate the superiority of intraoperative plasma-Lyte over other types of crystalloids about graft outcomes. 

Key Words: Kidney transplantation, fluid therapy, Plasma-lyte, acid-base balance, glomerular filtration rate

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INTRODUCTION 

Perioperative fluid management in patients undergoing kidney transplantation is crucial to maintain adequate intravascular volume, as well as acid-base and electrolyte balance, and may also affect graft tissue perfusion and function.1-3 Crystalloids, such as normal saline (NS) or balanced low-chloride solutions, are the most common and widely used fluids for intraoperative management to maintain optimal intravascular volume.4,5 Popotassium-containing fluids may theoretically cause hyperkalemia in patients during kidney transplantation; therefore, NS, which lacks potassium, is typically used during the perioperative period of kidney transplantation. However, rapid administration of a large volume of NS may lead to hyperchloremic metabolic acidosis and subsequent hyperkalemia.6-9 Hyperchloremia itself has also been reported as a risk factor associated with acute kidney injury.10-13

Considering the potential risk factors for acute kidney injury and adverse clinical outcomes, NS is being replaced with balanced crystalloid solutions as both resuscitation and maintenance crystalloids in critical care and perioperative fluid management.14-16 Half saline has been used as an intraoperative fluid during kidney transplantation instead of NS to prevent sodium retention and hyperchloremic metabolic acidosis in our hospital. Half saline may theoretically reduce the risk of hyperchloremic metabolic acidosis but may cause dilutional hyponatremia. Plasma-Lyte, one of several balanced crystalloids, is an isotonic, buffered solution with an electrolyte composition similar to that of human plasma.14 Plasma-lyte has a pH of 7.4 and has a lowerer chloride concentration than NS. In our hospital, there was a change in the intraoperative fluid from 0.45% half saline to Plasma-lyte.

Previous studies have compared the clinical effects of NS and balanced crystalloids in kidney transplantation.4,9,17-19 Balanced crystalloids showed a better metabolic profile. The effect of the type of intraoperative fluid type on postoperative graft function, however, remains uncertain. Meanwhile, tight control of intraoperative metabolic acidosis was reported to improve early kidney graft function.20 This study aimed to compare the effects of half saline and Plasma-lyte on acid-base and electrolyte balance and postoperative kidney graft function after living donor kidney transplantation.

MATERIALS AND METHODS 

Ethical considerations

This study was approved by the Institutional Review Board (IRB) of Severance Hospital (IRB No. 4-2020-0850). The requirement for informed consent was waived by the IRB due to the retrospective nature of this study.

Study design and patients 

This was a single-center, retrospective cohort study. Data were obtained from electronic medical records. Patients who underwent living donor kidney transplantation between January 2010 and December 2017 were enrolled, while those who underwent multi-organ transplantation were excluded. Patients were classified into two groups based on intraoperative fluid (half saline vs. Plasma-Lyte).

Demographics, perioperative fluid intake, and acid-base and electrolyte balance were compared between the two groups. Acid-base and electrolyte balance during surgery were recorded after induction of anesthesia (T0), reperfusion (T1), and during the immediate postoperative period (T2). Postoperative electrolyte concentrations were recorded on postoperative days (PODs) 1, 2, and 7. Daily urine volume and fluid balance were recorded until POD 2. Postoperative kidney graft function on PODs 1, 2, and 7 was assessed using serum blood urea nitrogen (BUN), creatinine, and estimated glomerular filtration rate (eGFR). eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.21 The eGFR values were calculated until 1 year post-transplantation to monitor graft outcomes. Delayed graft function was defined as the need for dialysis during the first week after transplantation. Renal biopsies were performed in cases of acute allograft dysfunction (>30% increase in serum creatinine levels, compared with the baseline value or proteinuria of >500 mg/day). Allograft biopsy samples were processed using light, immunofluorescent, and electron microscopy. All biopsy-proven acute rejections within the first 3 months post-transplantation were taken into account in the statistical analyses.

Intraoperative care 

Intraoperative anesthetic management was performed according to the standard protocols of the center. General anesthesia was induced with 1.5–2.5 mg/kg propofol and 0.6 mg/kg of rocuronium and was maintained with sevoflurane or desflurane (0.85–1.2 minimum alveolar concentration). Remifentanil was continuously infused at a rate of 0.1–0.3 μg/kg/min during surgery. The radial artery was catheterized for continuous blood pressure monitoring and arterial blood gas analysis. Either 0.45% half saline or Plasma-Lyte was used as an intraoperative maintenance fluid. The half-saline solution included sodium (77 mEq/L) and chloride (77 mEq/L). Plasma-Lyte (Plasma solution A, CJ Pharmaceutical, Seoul, Republic of Korea) contained sodium (140 mEq/L), potassium (5 mEq/L), magnesium (3 mEq/L), chloride (98 mEq/L), acetate (27 mEq/L), and gluconate (23 mEq/L). The intraoperative fluid choice was determined by our institute's protocol, which was changed from 0.45% half saline to Plasma-lyte after a discussion with surgeons and anesthesiologists. Fluid administration was guided by central venous pressure and adjusted by urine output after reperfusion of the kidney graft.

Postoperative care

Postoperative care was performed according to the standard protocols of our institute. Until discharge, 0.45% half saline and 0.9% NS with sodium bicarbonate (6 mEq/L) were used alternately during the postoperative period in both groups, depending on serum sodium levels. The immunosuppressive regimens used in our hospital are presented in Supplementary Table 1 (only online).

Statistical analyses Continuous variables are presented as means±standard deviations or medians (interquartile ranges). Categorical variables are presented as frequencies and proportions. Intergroup comparisons were performed using an independent t-test or a Mann-Whitney U test for continuous variables and Fisher's exact test or a chi-square test for categorical variables. Linear mixed models were used adjusting the first measured values between the two groups to analyze changes in perioperative acid-base balance, electrolytes, and parameters associated with kidney graft function. The first values of each parameter were taken as covariates. If there were differences in baseline characteristics between the two groups, we adjusted the differences by including baseline variables as covariates in the model. Nonparametric longitudinal analyses using the nparLD package in R were conducted. Bonferroni correction was used for multiple comparisons. Univariable and multivariable linear regression analyses were conducted to evaluate factors associated with graft function at 1 month and 1 year after transplantation. Risk factors found to be associated with kidney graft function in univariable analysis or those considered to be clinically relevant factors were included in the multivariable analysis. All analyses were performed using Statistical Analysis System (SAS) statistical software (version 9.1.3. SAS Institute Inc., Cary, NC, USA) and R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria). P values <0.05 were considered statistically significant.

RESULTS 

Of the 282 patients included in this study, 157 received half aline and 125 received Plasma-lyte during kidney transplantation. Significant demographic differences were observed between the groups, including recipient age, donor eGFR, ABO-incompatible donors, graft kidney weight to recipient body weight ratio, and amount of fluid administration during surgery (Table 1). There were no significant differences in delayed graft function and acute rejection between the groups.

Perioperative acid-base balance showed significant differences between the two groups after adjusting the first measured values by the linear mixed model (Table 2). Preoperative total CO2 levels were significantly higher in the half-saline group (p= 0.003). However, total CO2 levels during surgery were significantly higher in the Plasma-lyte group. The mean serum bicarbonate concentration (reference range, 21–28 mmol/L) was significantly higher in the Plasma-lyte group than in the half-saline group, even under physiologic ranges during the reperfusion (19.29±2.46 mmol/L vs. 22.93±3.48 mmol/L, p<0.001) and immediate postoperative periods (18.68±2.53 mmol/L vs. 21.85± 2.84 mmol/L, p<0.001). Base excess in the extracellular fluid was also significantly higher in the Plasma-lyte group than in the half-saline group during surgery. Sodium bicarbonate was administered in one patient in the half-saline group and no patients in the Plasma-lyte group (data not shown).

Hyponatremia (sodium <130 mmol/L) occurred more frequently in the half-saline group during the reperfusion period (p<0.001), immediate postoperative period (p<0.001), and POD 1 (p=0.032) (Table 3). Hyperchloremia (chloride >110 mmol/L) occurred more frequently in the half-saline group on POD 2 and 7, although there were no significant differences between the groups (p=0.163 and 0.067, respectively). Hyperkalemia (potassium >5.5 mmol/L) at the reperfusion period occurred in five patients in the half-saline group and one patient in the Plasma-lyte group, although the difference was not statistically significant (p>0.999).

Parameters associated with postoperative kidney graft function are shown in Table 4. We made a linear mixed model after adjusting for differences in baseline characteristics between the two groups to compare the parameters. Recipient age, donor eGFR, ABO-incompatible donors, graft kidney weight to recipient body weight ratio, amount of fluid administration during surgery, and the type of intraoperative fluid (half saline vs. Plasma-lyte) were included as fixed effects to evaluate the effect of fluid type on postoperative kidney graft function over time. BUN was lower at the immediate postoperative period (p<0.001), and creatinine was lower at the immediate postoperative period (p<0.001) and POD 1 (p=0.024). Urine volume was higher in the Plasma-lyte group at PODs 1 and 2 (p<0.001 for both). A significant difference was observed in BUN (p<0.001) and creatinine (p<0.001) change between groups over time (Fig. 1). As shown in Fig. 2, we found a significant difference between groups in eGFR change over time until 1-year after transplantation (p=0.006).

eGFR at 1 month was higher in the Plasma-lyte group (72.77± 23.67 vs. 61.83±20.05, p<0.001). Graft function measured by eGFR at 1 month after transplantation was associated with sex, intraoperative Plasma-lyte use, recipient age, donor age, donor graft kidney weight to recipient body weight ratio, acute rejection, and donor eGFR in the univariable model. In the adjusted model, patients who received Plasma-lyte during the intraoperative period exhibited a 9.156 mL/min/1.73 m2 higher eGFR at 1 month after transplantation (Table 5). eGFR at 6 months and 1 year was also higher in the Plasma-lyte group (74.04±19.27 vs. 63.92±18.64, p<0.001 and 71.83±19.65 vs. 66.20±19.80, p=0.018, respectively). Follow-up eGFR measured at 1 year post-transplantation was associated with sex, intraoperative Plasma-lyte use, donor age, donor graft kidney weight to recipient body weight ratio, acute rejection, and donor eGFR in the univariable model. Multivariable analysis revealed that intraoperative Plasma-lyte use was associated with a 4.452 mL/min/1.73 m2 higher eGFR at 1 year after transplantation (Table 6). Male sex was not significantly associated with eGFR at 1 month and 1 year after transplantation in multivariable analysis (p=0.093 and p=0.842, respectively).

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