Effect of donor and recipient preoperative serum sodium on prognosis of liver transplantation

In this study, LT donor and recipient sodium dysnatremia did not affect postoperative survival, liver and renal function, but in recipients with higher serum sodium concentrations than the donor, 1-week post-operative TBIL and DBIL were found to be significantly higher at time point.

A systematic review including 25 cohort studies involving 19,389 patients found that donor dysnatremia was associated with liver graft dysfunction in the early postoperative phase but had a negative impact on recipient survival. were shown to be unrelated.⁷. However, a study of 212 patients showed that donor hypernatremia was a poor prognostic factor for LT survival in donors older than 70 years.¹⁸. The prognostic impact of donor hypernatremia is related to the duration of serum sodium elevation, with duration <36 hours having no effect on graft and recipient 1-year postoperative survival However, duration less than 36 hours had a significant negative effect on prognosis. 36 hours or more⁸. Our finding that donor serum sodium did not influence the prognosis of LT was consistent with the results of several previous clinical studies^{8, 10}. Inconsistent criteria for defining hypernatremia may account for the differences in results. Immunosuppressive therapy after LT plays an important role in preventing postoperative rejection, and using too little or too much anti-rejection drug may cause abnormal liver function. Currently, each transplant center's immunosuppressive regimen is different, and our center's immunosuppressive regimen is detailed in the methods section. However, we do not know whether our regimen is better than other regimens, and we believe that this may be one of the reasons for the difference in study results.

Approximately 22% of patients with cirrhosis progress to hyponatremia, primarily due to dilutional hyponatremia followed by hypoproteinemia and inappropriate diuretic administration.^17,19. Hyponatremia is an independent risk factor for death in patients on the LT waiting list¹¹MELD-Na score after adding serum sodium to MELD score can better predict mortality risk in recipients awaiting transplantation.^14,20. Our study shows that preoperative hyponatremia in recipients is associated with decreased preoperative liver and renal function, but does not affect prognosis, which may be associated with many This is consistent with the results of the study.^{twenty one}. However, some studies have also reported that elevated preoperative serum sodium levels increase mortality in recipients awaiting LT.^{twenty two}hypernatremia is associated with preoperative renal failure.^{twenty three}. Inconsistent classification criteria for serum sodium and different durations of serum sodium abnormalities may be some of the reasons for the differences in study results.

Many studies have reported that preoperative donor hypernatremia has a negative effect on postoperative liver function, and preoperative recipient hyponatremia is also a factor in poor prognosis. It is one. Therefore, we speculated that transplanting a hypernatremic donor liver into a hyponatremic recipient might have a more negative impact on prognosis, but the results were contrary to our speculation. In this study, we combined preoperative donor and recipient serum sodium to analyze for the first time the effect of delta serum sodium on LT. The results showed that donor liver transplantation into recipients with high serum sodium concentrations resulted in significantly higher TBIL and DBIL after 1 week. However, delta serum sodium did not affect long-term prognosis. In a study of 54,311 LT patients, recipient preoperative hypernatremia significantly reduced patient and graft survival at 90 days postoperatively, whereas recipient preoperative hyponatremia was shown to have no effect on postoperative patient or graft survival.¹²This was associated with our finding that serum sodium increased after LT, leading to a poor prognosis. Further pairwise comparisons of TBIL and DBIL at 1 week postoperatively were made between the delta sodium groups.< 0 mmol/L 群と 0 ～ 10 mmol/L 群で有意差が示された。デルタナトリウム > TBIL and DBIL in the 10 mmol/L group were not significantly different from other groups, but the mean values ​​were higher than those in the 0-10 mmol/L group. Sodium concentrations between donor and recipient can also negatively impact postoperative liver function.

The mechanism of elevated serum sodium leading to liver dysfunction has not been reported. A possible molecular mechanism is that increased serum sodium exacerbates liver inflammation and apoptosis. Elevated serum sodium has been shown to activate epithelial sodium channels (ENaC), which promote sodium entry into cells.^{twenty four,twenty five,26}. Compared with rats fed with normal water, rats fed with high sodium water had more severe renal ischemia-reperfusion injury and significantly higher expression of ENaC in the kidney. Application of amiloride, an ENaCs inhibitor, may effectively alleviate renal damage exacerbated by hypernatremia^{twenty five}. In cystic fibrosis, excessive activation of ENaC increases intracellular sodium in airway epithelial cells, increases levels of NLRP3 inflammasome, IL-18, and IL-1β, and worsens airway inflammation.^{twenty four}. Hypernatremia promotes the expression of NLRP3 inflammasome and IL-1β in vascular endothelial cells, leading to hypertension and cardiovascular disease. Its effect is achieved by activating ENaC and Na.⁺/Ca²⁺ Exchange (NCX)²⁶. NCX is a channel that mediates calcium and sodium exchange within the cell membrane, and after cardiac ischemia-reperfusion, the expression of NCX in cardiomyocytes increases significantly, and application of NCX inhibitors inhibits cardiac ischemia-reperfusion injury. can be clearly reduced.²⁷. A possible mechanism is that when a liver is transplanted into a recipient with a higher serum sodium concentration than the donor, the sodium concentration within the hepatocyte environment increases, resulting in activation of ENaC, and extracellular sodium transfer via ENaC. It means entering cells. rose. Elevated intracellular sodium increases intracellular calcium via NCX, and intracellular calcium excess activates apoptotic and inflammatory signaling pathways, resulting in exacerbation of liver inflammation and increased hepatocyte death.

At the same time, increased extracellular sodium can enter cells through other sodium channels such as sodium hydrogen exchanger-1.²⁸ Sodium-glucose cotransporter-2²⁹resulting in an increase in intracellular sodium. Sodium is very important for maintaining cell morphology and mass exchange.^30,31an increase in intracellular sodium leads to an imbalance in ion homeostasis and impaired cellular metabolism, which may be one of the mechanisms of worsening liver injury.

As this is a single-center study, the number of included cases is limited and may introduce bias. This study did not further investigate postoperative complications that may need to be improved. There is no internationally uniform classification standard for donor and recipient serum sodium, which can lead to some degree of confusion. This study on serum delta sodium in donor-recipient pairs is suggestive and further studies on serum delta sodium in larger samples are needed.

In conclusion, this study shows that TBIL and DBIL are significantly elevated early postoperatively in recipients with higher serum sodium concentrations than the donor, which may influence how donor livers should be allocated. may provide some guidance regarding