The most important finding in this study was the correlation between renal function and PTHL, which may be of great help in better understanding the pathogenesis of PTHL, and as much as possible, preventing its development. It was demonstrated that post-transplant serum creatinine had a significant positive correlation with serum triglycerides both in the first and third post-transplant month. More importantly, using multivariate regression analysis, ERD was found to be an independent risk factor for PTHL. Patients with ERD usually had a relatively long-term and severe renal insufficiency before transplantation, and impaired renal function resolved very slowly during the first six months after transplantation. Here, we provide the first evidence that delayed recovery of renal function after transplantation, which was probably due to chronic kidney injury before transplantation, can result in PTHL, especially hypertriglyceridemia.
In fact, it is well known that chronic kidney disease is associated with hyperlipidemia. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma proteins[19
]. Therefore, hyperlipidemia induced by impaired renal function is characterized by abnormal metabolism of plasma lipoproteins[20,21
]. The reduced catabolic rate of triglyceride-rich lipoproteins and the growing hepatic production of triglyceride-high lipoproteins may explain why hypertriglyceridemia is one of the most common quantitative lipid abnormalities in patients with chronic kidney disease[22,23
]. Consistent with previous findings, the impaired renal function and recovered liver synthetic function in patients with ERD during the early post-transplant period may explain the development of hypertriglyceridemia in this study. Therefore, more emphasis should be placed on this issue, as more and more patients are undergoing liver transplantation with higher serum creatinine levels in the era of MELD.
Another finding in this study was that graft function was associated with cholesterol metabolism after LDLT. Our results showed the smooth recovery of decompensated liver function during the early post-transplant period. Furthermore, elevated serum cholinesterase level, which represents the recovery of hepatic cellular synthetic function, was significantly correlated with an increase in cholesterol level within the normal range. It is noteworthy that cholesterol plays an active role during liver regeneration. It is not only a structural component, but also a significant regulator in the control of the intermediate metabolism of different liver cell types[24
]. This implies that there may be mutual benefits between improved graft synthetic function and cholesterol homeostasis.
Since donor pre-transplant serum lipid level may play an essential role in the development of PTHL[25
], we also analyzed the association between pre-transplant donor serum lipid level and post-transplant recipient serum lipid level. No significant difference in the incidence of PTHL was found between the recipients receiving grafts from pre-transplant hyperlipidemic and non-hyperlipidemic donors. The pre-transplant serum triglyceride and cholesterol levels of donors in the PTHL group were not significantly higher than those in the non-PTHL group. Therefore, in this study, there was no obvious evidence to show that pre-transplant donors’ serum lipid level or fatty liver exerted crucial effects on the development of PTHL.
High BMI was found to be another independent risk factor for PTHL in this study. As a main component of the metabolic syndrome, high BMI or obesity before LT has been reported to be associated with an increased prevalence of PTHL[26
]. It seems unlikely that dietary habits and unhealthy lifestyle can be changed and thus patients retain their obesity status, resulting in abnormalities in lipid metabolism. It was notable that some patients had pre-transplant hyperlipidemia, but did not have PTHL in this study. A possible reason for this is that pre-transplant hyperlipidemia, which resulted mainly from hepatorenal syndrome due to end-stage liver disease, could be improved or resolved by the recovery of liver and kidney function after liver transplantation.
A high blood concentration of tacrolimus has been reported to contribute to PTHL in LDLT[27
]. However, in the present study, we did not find an association between immunosuppressive drugs and PTHL. This may be due to the early steroid withdrawn and low tacrolimus concentration protocol. Furthermore, reduced-dose tacrolimus with or without an IL-2 receptor blocker was given to patients who developed post-transplant renal impairment, which also minimizes the side-effects of immunosuppressive drugs on lipid metabolism.
There were some limitations in this study. Firstly, it was not a prospective study. The impact of graft and kidney function on the development of PTHL requires confirmation in prospective studies with larger samples. Secondly, a longer period of follow-up is necessary to identify the natural history of PTHL and to determine the influence of PTHL on a recipient’s prognosis. Thirdly, a study at the molecular level should be performed as the donor’s genotype may play a role in the development of metabolic diseases.
In conclusion, renal and graft function correlated with lipid metabolism after LDLT. Severe pre-transplant renal insufficiency may lead to long-term post-transplant renal dysfunction, and consequently cause PTHL, especially hypertriglyceridemia. Appropriate clinical treatment such as the prophylactic use of fibrates or statins may be considered to prevent PTHL in patients who develop ERD or have longstanding pre-transplant renal dysfunction. Well-designed and large-sample studies are needed to verify these results.