In this population-based observational study, we found that moderate alcohol consumption was negatively associated with a significant decline in kidney function in men with nonalcoholic fatty liver disease. Results were only slightly attenuated after adjusting for a potential covariates in model 4, suggesting that these factors (diabetes, BMI, ALT, AST, SBP, and DBP) may not totally explain the connection between alcohol consumption and CKD. In fact, unadjusted ORs were also significantly lower in binge alcohol drinkers(drinking more than or equal to 1.4 drinks per day ); however, this association was not observed in models adjusted for diabetes mellitus, ALT, AST, BUN and other laboratory parameters. The lower risk of adverse renal outcomes was not found in binge drinkers. These findings suggest that metabolic conditions are important determinants of the relationship between alcohol consumption and CKD progression in NAFLD. However, we failed to find any effect of moderate alcohol consumption on kidney function in women with NAFLD.
CKD remains a worldwide public health burden, which affects up to 10–15% of the general population and over 25% of individuals older than 65 years27. The features of the metabolic syndrome, especially obesity, diabetes, and hypertension, are risk factors for NAFLD, making it difficult to represent a relative association between the diagnosis of fatty liver disease and the development and progression of renal disease28.However, there is accumulating evidence to support NAFLD play a causative role in the development of chronic kidney disease.A recent meta-analysis of thirty-three studies with a total of over 2000 participants found that NAFLD was associated with an increased prevalence odd ratio (OR) 2.12 as well as incidence hazard ratio (HR) 1.79 of CKD. An abdominal ultrasonography-based cross-sectional investigation of Chinese people found a high correlation between NAFLD and the risk of CKD prevalence and abnormal albuminuria.29. A increasing amount of epidemiological research indicates that NAFLD exacerbates visceral obesity, atherogenic dyslipidemia, and hepatic insulin resistance, which results in the release of several proinflammatory cytokines and hepatokines that may aid in the onset and progression of CKD.30,31.
Prior research on the impact of alcohol in NAFLD patients typically assessed the prevalence or severity of liver disease. Even though there is evidence that suggests people with NAFLD may benefit from moderate alcohol use, the relationship between alcohol use and kidney function in these patients has not been sufficiently researched. Our findings in this cross-sectional study regarding the protective effects of moderate alcohol consumption on a slower decline in eGFR in this population are in line with the findings of these studies, which demonstrate a protective effect of moderate alcohol consumption on the onset and severity of kidney disease. A study recruiting 4664 participants from the China Health and Nutrition Survey(CHNS) found that alcohol consumption showed a U-shaped association with CKD and moderate drinkers exhibited a lower CKD prevalence compared with non-drinkers and heavy drinkers20.More regular alcohol use and binge drinking were linked to a smaller reduction in eGFR over 12 years, especially in men, according to a recent population-based prospective cohort study in Korea.32.A meta-analysis included 20 studies with 292431 patients to assess the relationship between high alcohol consumption and progression of kidney damage. It indicated an inverse association between high alcohol consumption and CKD in healthy adult males, with an overall 0.72-fold decreased risk of CKD compared to those who did not regularly consume alcohol. However, there is no significant association between high alcohol consumption and proteinuria33.Similarly, In our study, there were significant gender differences in the correlation between modest alcohol consumption with the development of CKD, where the favorable effect was observed among only men with nonalcoholic fatty liver disease. In light of our findings, it is possible that moderate alcohol use can help lower the risk of incident CKD in both NAFLD patients and the general population.
The physiological mechanisms of the protective effect of alcohol on the decline in kidney function are not fully illuminated, but several reasonable evidences may explain this interesting phenomenon. Firstly, some researchers have demonstrated that alcohol intake may play a role in increasing high-density lipoprotein (HDL) levels34,35.One prospective study reported that low HDL cholesterol increased CKD risk36. To some extent, the increase in HDL effect may play an important role in the inverse association of CKD with high alcohol consumption. Secondly, modest alcohol consumption is associated with plasminogen activator inhibitor-1declining, which means higher plasma endogenous tissue-type plasminogen activator levels and decreasing platelet aggregation to prevent extracellular matrix accumulation and finally improve renal function37.Thirdly, red wine and other alcoholic beverages include polyphenolic chemicals that exhibit anti-oxidant and anti-inflammatory characteristics in animal models. These features may both preserve kidney function by activating the enzymes glutathione peroxidase, catalase, and superoxide dismutase.38–40. Fourthly, alcohol consumption has beneficial effects on insulin and insulin sensitivity in postmenopausal women41,42.The improvement in insulin sensitivity brought on by alcohol use may be advantageous to kidney function, given that insulin resistance and the attendant hyperinsulinemia are linked to renal impairment in the general population43,44. Other mechanisms may be mediated by the positive influences of alcohol on antioxidant enzymes, atherosclerosis, as well as renal arteriolar hyalinization45–48.While the exact biochemical mechanism underlying the sex differences in the consequences of alcohol intake is still unknown, oxidative stress, which is known to be more prevalent in men than women, can help to explain some of the disparities. Furthermore, male rats had much higher renal indicators of oxidative stress than female rats49,50. As a result, men may benefit more from the antioxidant effects of alcoholic beverages on the kidney.
One must be aware of the possible adverse effects associated with moderate drinking despite these potential benefits mentioned above, such as risk of breast and colon cancer51,52.Alcohol consumption may also be associated with a wide range of social problems, including traffic injuries, and a risk of progression to problem drinking53.Considering these potential risks, the World Health Organization recommends that alcohol consumption should not be utilized as a preventive strategy for other health benefits54. In summary, heavy alcohol consumption has many harmful effects and should be discouraged regardless of whether a person has NAFLD or not. However, emerging epidemiological data suggest that light to moderate drinking may have favorable effects. The current study is cross-sectional, and prospective studies should be used to further evaluate the temporal association or causality between moderate alcohol intake and incidence CKD in NAFLD. As a result, it is safe to advise NAFLD patients who have never used alcohol to do so going forward. The question of whether abstinence from alcohol should be advised to NAFLD patients who are moderate drinkers, particularly for those with mild (10 g/d) drinking, still has to be answered.
It is important to recognize that our study has a number of limitations. First, even though the models were corrected for potential confounders, there might still have been residual confounding due to the observational character of our study.The power and generalizability of our study, however, have increased since we were able to analyze a sizable sample of the American population using a model based on readily available anthropometric and laboratory data. Alcohol cannot be used in human studies as an experimental intervention due to ethical concerns, hence the hypothesis must be carefully examined using high-quality prospective observational data.Second, the amount or frequency of alcohol consumption was self-reported, which is subject to reporting bias and may have been under-reported due to negative sociocultural perceptions about heavy drinking. Additionally, alcohol use frequency and/or volume may alter over time. Our estimations should be modest, nevertheless, given that higher alcohol consumption seems to be linked to improved kidney function preservation. Third, because the diagnosis of NAFLD was established using the HSI biochemical model rather than a tissue biopsy, some of the study subjects may have been misclassified. Additionally, we only evaluated daily alcohol use; nonetheless, determining drinking patterns or habits is crucial for determining alcohol use. Therefore, the ideal cutoff level for moderate drinking in NAFLD men cannot be determined by this investigation. It is yet unknown how much alcohol is safe for NAFLD guys to consume.