In the present study, we found that higher baseline AST/ALT ratio may carry an increased risk of CVD and all-cause mortality in PD patients. Also, even though we excluded those patients with chronic liver disease, or a history of CVD, PD patients at the commencement of PD may have a higher prevalence of high AST/ALT ratio. PD patents have high risk of CVD episodes and liver disease, suggesting patients may have unknown underlying cardiovascular disease or liver disease. We should cautiously explain the association between AST/ALT ratio and CVD mortality.
Aminotransferase, including AST and ALT, is a well-known marker for liver injury. AST is in both the liver and myocardial tissue, but ALT is only in the liver . The elevation of the AST/ALT ratio is due to induction by alcohol consumption and cardio-hepatic interaction [16, 24]. As compared to participants with a lower AST/ALT ratio, those with a high AST/ALT ratio had a higher pre-existing CVD prevalence, indicating a higher AST/ALT ratio may implicit heart damage and overload, as well as underlying CVD episodes . The Japanese study of 3,494 participants more than 40 years found that the high AST/ALT ratio had an independent association with all-cause and CVD mortality, with a 10-year follow-up . In this study, participants with end-stage renal disease, incomplete data, or study withdrawal were excluded, but those with alcohol habits or pre-existing CVD were not excluded, suggesting less convincing of their findings due to selective bias. The Italy 6-year follow-up study with 2529 diabetes showed that the AST/ALT ratio had an independent association with all-cause and CVD mortality. Patients with a known history of drug-induced liver injury, viral hepatitis, cirrhosis of any etiology, and hemochromatosis were also excluded, but those with a history of CVD failed to be excluded in this study . More recently, a 10-year follow-up prospective study of 29,316 participants aged between 25 and 84 years from the United Kingdom showed that an increased AST/ALT ratio were at significant risk of developing CVD episodes in male participants but not those female, with no baseline pre-existing CVD . Nonetheless, when added to the traditional CVD prediction tools such as Framingham Risk Scores, the AST/ALT ratio did not contribute to any extra benefits in predicting the CVD accuracy. The major limitation was that patients with chronic liver disease were not excluded from this study. In the present study, to reduce selection bias, we excluded those current drinking, liver disease, and those with a history of CVD. We found that a higher AST/ALT ratio was independently associated with an increased risk for CVD and all-cause mortality. PD patients with a high AST/ALT ratio may have a 1.43-fold higher risk of CVD mortality and a 1.45-fold higher risk of all-cause mortality compared with their counterparts, even after adjustment for confounding factors. Subgroup analyses showed that a high AST/ALT ratio remained an independent predictor for CVD mortality in those male and non-hyperlipidemias, and all-cause mortality in those non-diabetes, hypertension, and non-hyperlipidemias. These findings suggested, along with previous studies, that PD patients with a higher AST/ALT ratio may have more CVD and all-cause involvement, and a preprocedural AST/ALT ratio, a widely available and inexpensive biomarker, might be helpful for risk stratification of CVD and all-cause mortality in PD patients.
A previous study reported that the prevalence of high AST/ALT ratio ≥1.0 was 37.9% in 2529 type 2 diabetes patients with a 6-year follow-up . Patients with chronic liver diseases were excluded, but those with a history of CVD were not excluded from this study, which may lead to an over-estimated prevalence of high AST/ALT ratio. To date, the prevalence of the high AST/ALT ratio in dialysis patients has received little attention. In the present study, we excluded those with chronic liver disease or a history of CVD, which may be considered as an essential reason to increase the AST/ALT ratio. Nonetheless, the prevalence of a high AST/ALT ratio was 76.6% in the cohort study and ranged from 68.4% to 86.9% among all subgroups. Thus, there might be a higher prevalence of high AST/ALT ratio in PD patients. These findings suggested, along with previous studies, that future studies should further investigate the prevalence of the AST/ALT ratio in dialysis patients and whether the prognosis of PD patients might be improved by the management of the high AST/ALT ratio.
ALT has potential value as a novel biomarker of aging . Decreased ALT resulted from a reduced liver size and liver blood flow and was associated with aging, frailty, and higher mortality in the general elderly population [26, 27]. There is a correlation between ALT levels and the severity of renal failure . Patients on dialysis had reduced serum levels of aminotransferases, which suggested that the ALT levels were reduced concomitantly with the progression of renal dysfunction [14, 15]. Previous study demonstrated that ALT levels have a negative correlation with the severity of renal failure, resulting in high AST/ALT ratio in PD patients. In the present study, The ALT levels were reduced concomitantly with the progression of renal dysfunction, resulting in high prevalence of AST/ALT in PD patients. Thus, whether management of AST/ALT ratio can improve the prognosis of PD patients is worth further evaluation.
This study has some limitations. First, we retrospectively reported the independent association, but not causal relationships, between the AST/ALT ratio and the interesting points. We can not adjust all confounding factors of CVD and all-cause mortality, and not eliminated completely the residual confounding effect. Nonetheless, given the effect of residual confounding on the interesting outcomes, we adjusted for potential risk factors using multiply regression analysis. Second, PD patients usually took multiple drugs simultaneously due to other complications. So, it was difficult to determine which drugs may influence liver aminotransferase because of the interaction of drugs. Although we failed to exclude those patients whose liver aminotransferase may influence by multiple drugs, those with AST or ALT values ≥two times higher than normal values were excluded. Thus, the effect of drugs on liver aminotransferase may be minimized. Third, rare chronic diseases such as hemochromatosis, which may influence aminotransferase activity, failed to be excluded in the present study. Fourth, we only evaluated baseline variables rather than changes over time in these variables of CVD and all-cause mortality. Additionally, With the development of PD technique, medications, and the treatment of other complications, the prognosis of PD patients have been dramatically improved. Thus, changes over time may affect the results of PD patients, suggesting those receiving more advanced composited managements may gain more benefits than those ante-counterparts. Finally, because PD patients were all Chinese in the present study, the results may not apply to other ethnic PD patients.