Alcohol Consumption and Nonalcoholic Fatty Liver Disease: Effects on Chronic Kidney Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease which is regarded as a separate risk factor for chronic kidney disease (CKD).Moderate alcohol consumption has been shown to reduce all-cause mortality in patients with NAFLD. Participants of ten rounds of the continuous National Health and Nutrition Examination Survey (NHANES:1998-2018) were included in this study. Participants with an HSI score more than 36 were considered to have NAFLD, which was determined using the Hepatic Steatosis Index (HSI) model. Multivariate logistic regression models were used to evaluate the effects of moderate alcohol consumption on CKD in both male and female populations. Subgroup analysis was performed after classifying patients with NAFLD by using the Fibrosis-4 (FIB-4) index.There were 17040 participants that qualified to take part in the study.The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and P <0.001. After further adjustment for diabetes mellitus, ALT, AST, AKP, BUN, UA, HSI, TC and HDL-c, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low-fiber-risk, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, P=0.02), but the association was not significant in the high-fiber-risk group. Interestingly, patients with NAFLD who were at high risk of fibrosis showed a significant trend in favor of consuming more than or equal to 1.4 drinks per day (OR = 0.34, 95% CI 0.13-0.87, P=0.03).In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group. Taken together, moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.

Introduction

NAFLD has become the most common chronic liver disease worldwide, around 25% of the global adult population is being affected¹. Its prevalence is expected to increase each year as urbanization progresses and the prevalence of components such as obesity and diabetes, increases. NAFLD is characterized by the presence of ⩾5% hepatic fat accumulation after excluding excessive alcohol consumption and other common causes of chronic liver disease (e.g., viral or autoimmune hepatitis). NAFLD can proceed to liver fibrosis, cirrhosis, and even hepatocellular cancer. It is classified as either nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver (NAFL).²

As a multi-system disease³, NAFLD is considered as an independent risk factor for cardiovascular disease, while there is growing evidence supporting its pathogenic role in the development of chronic kidney disease (CKD)^4–6, and the development of fibrosis may be associated with increased incidence risk of CKD⁷.

As a risk factor for end-stage renal disease and cardiovascular disease, chronic kidney disease can also lead to considerable morbidity and mortality, making it a major medical challenge worldwide⁸.Both NAFLD and CKD share a number of cardiorearenal risk factors, including diabetes mellitus, obesity, dyslipidemia, and hypertension^9–11. Moreover, many studies have shown that alcohol consumption also affects the prognosis of patients with CKD.

Chronic alcohol consumption has become a major global health threat. However, there is evidence that moderate alcohol consumption is associated with a low incidence of intrahepatic fibrosis and NASH¹², and it also reduces all-cause mortality in patients with NAFLD¹³.Several clinical studies and meta-analyses have shown that in the general population, moderate drinkers have a lower prevalence of CKD when compared with non-drinkers and heavy drinkers^14–20, which may be related to the fact that alcohol can improve insulin sensitivity²¹and protective lipoprotein levels and reduce inflammation²². However, there are no relevant studies about the effect of alcohol consumption on CKD in NAFLD patients, it remains to be verified whether this protective effect can be extended to NAFLD patients.

Therefore, this study aimed to evaluate the effects of alcohol consumption on the development of chronic kidney disease in patients with non-alcoholic fatty liver disease.

Participants And Methods

Participants of ten rounds of the continuous National Health and Nutrition Examination Survey (NHANES:1998–2018) were included in this study. Ethical approval was obtained through the National Center for Health Statistics Research Ethics Review Board (CDC,1999) research ethics review board. All procedures conformed to the tenets of the Helsinki Declaration of 1975 (revised in 2013) and written informed consent was obtained from all participants. The following participant-specific data were gathered: demographics, body mass index (BMI), systolic and diastolic blood pressure, pregnancy, cancer, hepatitis B and hepatitis C virus serology, liver transaminases, alcohol use, serum cotinie, blood glucose, Creatinine, urea nitrogen, eGFR, diagnosis of diabetes mellitus, diagnosis of hypertension, diagnosis of coronary heart disease, use of (such as amiodarone, corticosteroids, methotrexate, tamoxifen and valproate).

Participants in the NHANES who had any of the following conditions were disqualified: significant alcohol use (defined as more than three drinks per day for men and more than two drinks per day for women), hepatitis B or hepatitis C positivity on a serology test, use of steatogenic medications for longer than six months, cancer, and pregnancy (Fig. 1). In the remaining participants, NAFLD was then determined using the Hepatic Steatosis Index (HSI) model. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratios, BMI, gender, and the presence or absence of diabetes are all factors that can be used to predict the presence of NAFLD. The formula for HSI is as follows: HSI = [8 (ALT/AST ratio) + BMI (+ 2 if female; +2 if diabetes mellitus)].

The area under the receiver operating characteristic curve for this model is 0.81 (95% confidence interval [CI] 0.80–0.82), with a specificity of 92.4% for the identification of NAFLD in patients with values > 36^(23,24). Our definition of the existence of NAFLD as an HSI score greater than 36 followed the cutoff values utilized in the validation research.

Based on the creatinine equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the estimated glomerular filtration rate was used to diagnose CKD. According to the Kidney Disease Outcome Quality Initiative (KDOQI) standards, patients were classified as having CKD if their eGFR was lower than 60 mL/min/1.73 m² at the time of study enrollment²⁵.

Alcohol use is defined according to the references¹³, briefly, Alcohol usage was determined by averaging the number of drinks drunk each day over the preceding 12 months, taking into account both the average number of days that participants reported drinking and the average daily intake. Twelve ounces of beer, five ounces of wine, or eleven and a half ounces of liquor were considered to be one drink. In order to evaluate the effects of alcohol on chronic kidney disease (CKD), alcohol consumption was divided into three categories: less than half a drink per day (reference group, here referred to as nondrinkers), between half a drink and less than one and a half drinks per day (here referred to as moderate alcohol consumption), and more than or equal to 1.4 drinks per day (called excessive drinkers here). Diabetes was regarded as having a fasting plasma glucose level above 126 mg/dL, using oral hypoglycemic medications or insulin, or having been officially diagnosed by the participant's healthcare professional. The race of the participants was divided into Mexican American, Hispanic, Non-Hispanic White, Non-Hispanic Black, and Other Race categories. Based on previous validation studies in patients with NAFLD²⁶, the Fibrosis-4 (FIB-4) index for liver fibrosis was used to divide patients with NAFLD into two groups: low fibrosis risk (FIB-4 1.79; high fibrosis risk (FIB-4 > 1.79; see table below) and high fibrosis risk. Participants with missing covariate data were not included in the study (Fig. 1).

Numbers(%), means(SD), and medians are used to present data (interquartile range [IQR]). To compare groups in a univariate study, student t and chi-squared tests were utilized. Logistic regression analyses were used to assess the association between CKD, alcoholic use, and clinical risk factors. A minimum adjustment for age and ethnicity was determined upon for the analysis. A completely adjusted analysis was also conducted, taking into

account age, ethnicity, BMI, systolic and diastolic blood pressure, diabetes, ALT, AST, AKP, BUN, UA, HSI, TC, and HDL-c All analyses were conducted to account for the complex survey design, and all estimates were weighted. The significance level for each test is alpha = 0.05, and all tests are two-tailed. In R Studio (version 4.2.0; R Studio Team), all statistical calculationswere carried out.

Results

17040 people were qualified to participate in the trial after those with severe alcohol use, hepatitis B or C, steatogenic medication usage, or missing data on variables were disqualified. Of those, 8956 patients (53%) were women and 8075 patients (47%) were men (Fig. 1). A total of 1098 patients had chronic kidney disease(CKD),and CKD occurred in 270 men and 828 women. The characteristics of the study population are given in Table 1. In men with NAFLD, Compared with non-drinkers, moderate drinkers were younger, had lower BMI and systolic blood pressure, lower eGFR and creatinine, and lower fasting blood glucose and glycosylated hemoglobin, and lower alkaline phosphatase(AKP). Conversely, alanine aminotransferase(ALT), aspartate aminotransferase(AST), glutamyl aminotransferase(GGT), serum uric acid(UA), albumin, and total protein were higher than non-drinkers.In men who drink moderately, TC and HDL-c are higher, and HSI is lower. In women with NAFLD, Compared with non-drinkers, moderate drinkers were younger, had lower BMI, AKP, AST, AKP, triglycerides(TG) and HbAlc, and higher total cholesterol(TC) and high-density lipoprotein(HDL-c) levels.UA, HSI, and FIB-4 were lower in moderate drinking women.

A model of logistic regression analysis was performed using the presence of CKD as a dependent variable(Table2).Moderate alcohol use was a protective factor for men with NAFLD, with an unadjusted OR of 0.37 (0.22, 0.65), P < 0.001.After adjusting for age and race, the OR was 0.45 (0.26, 0.79),P = 0.01(model2).After further adjustment for BMI, systolic pressure, and diastolic pressure, the OR value was 0.50 (0.28, 0.87),P = 0.02(model3).The association persisted after finally correcting for diabetes mellitus, ALT, AST, AKP, BUN, UA, HSI, TC and HDL-c, the OR value was 0.36(0.17,0.76),P = 0.01(model4). Moderate alcohol use was also a protective factor for women with NAFLD, with an unadjusted OR of 0.67(0.47,0.95), P = 0.03(model1), but it vanished after other covariates were taken into account.

Furthermore, using the FIB-4 index for liver fibrosis, we evaluated how drinking alcohol affected individuals with NAFLD's CKD risk. Moderate alcohol consumption continued to show a protective effect on CKD in patients with NAFLD who had low risk of fibrosis in men (OR = 0.32, 95% CI 0.12–0.84, P = 0.02) (Table 3).The same analysis in NAFLD patients with high risk of fibrosis failed to show any significant effects for moderate alcohol consumption and showed a nonsignificant trend toward benefit (OR = 0.25,95%CI 0.06–1.06,P = 0.25).Intriguingly, patients with NAFLD and high fibrosis risk exhibited a significant trend toward benefit when they drank more than or equivalent to 1.4 drinks per day (OR = 0.34, 95% CI 0.13–0.87, P = 0.03). However, In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group (Table 4).

In male patients with NAFLD, a forest plot showing OR values and 95% confidence intervals from the multivariable logistic regression model evaluating the effects of alcohol consumption on CKD (Fig. 2).The final nomogram prognostic model was created using the resulting multivariate logistic regression model, which also served to determine the risk score (Fig. 3).

Discussion

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) levels^34,35.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 women^41,42.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 population^43,44. Other mechanisms may be mediated by the positive influences of alcohol on antioxidant enzymes, atherosclerosis, as well as renal arteriolar hyalinization^45–48.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 rats^49,50. 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 cancer^51,52.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.

Declarations

Author contributions

TZ, XW and GT designed the study. TZ, XW analyzed and interpreted the data. CL and KK drafted the manuscript. KK, DW, BW, PG, YH and GT revised the manuscript. All authors gave final approval of the final version to be published.

Data availability statement

The datasets generated and analysed during the current study are available in the NHANES database: https://www.cdc.gov/nchs/nhanes/index.htm

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

1. Chalasani N, Younossi Z, Lavine J E, et al., The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases [J]. Hepatology, 2018, 67(1): 328–57.
2. Younossi Z, M, Koenig A, B, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes [J]. Hepatology, 2016, 64(1): 73–84.
3. Byrne C D, Targher G. NAFLD: a multisystem disease [J]. Journal of hepatology, 2015, 62(1): S47-S64.
4. Cai X, Sun L, Liu X, et al. Non-alcoholic fatty liver disease is associated with an increased risk of chronic kidney disease [J]. Therapeutic Advances in Chronic Disease, 2021, 12: 20406223211024361.
5. Marcuccilli M, Chonchol M. NAFLD and chronic kidney disease [J]. International journal of molecular sciences, 2016, 17(4): 562.
6. Önnerhag K, Dreja K, Nilsson P, M, et al., Increased mortality in non-alcoholic fatty liver disease with chronic kidney disease is explained by metabolic comorbidities [J]. Clinics and research in hepatology and gastroenterology, 2019, 43(5): 542–50.
7. Tao Z, Li Y, Cheng B, et al. Influence of Nonalcoholic Fatty Liver Disease on the Occurrence and Severity of Chronic Kidney Disease [J]. Journal of Clinical and Translational Hepatology, 2022, 10(1): 164.
8. de Boer I H, Caramori M L, Chan J, C, et al., KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease [J]. Kidney international, 2020, 98(4): S1-S115.
9. Jespersen T, Kruse N, Mehta T et al., Light wine consumption is associated with a lower odds for cardiovascular disease in chronic kidney disease [J]. Nutrition, Metabolism and Cardiovascular Diseases, 2018, 28(11): 1133–9.
10. Umesawa M, Sairenchi T, Haruyama Y et al., Validity of a risk prediction equation for CKD after 10 years of follow-up in a Japanese population: the Ibaraki prefectural health study [J]. American journal of kidney diseases, 2018, 71(6): 842–50.
11. Tomiyama C, Higa A, Dalboni M A, et al., The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients [J]. Nephrology Dialysis Transplantation, 2006, 21(9): 2464–71.
12. Kwon I, Jun D W, Moon J-H. Effects of moderate alcohol drinking in patients with nonalcoholic fatty liver disease [J]. Gut and liver, 2019, 13(3): 308.
13. Hajifathalian K, Torabi Sagvand B, McCullough A J. Effect of alcohol consumption on survival in nonalcoholic fatty liver disease: a national prospective cohort study [J]. Hepatology, 2019, 70(2): 511–21.
14. Lai Y-J, Chen Y-Y, Lin Y-K, et al., Alcohol consumption and risk of chronic kidney disease: a nationwide observational cohort study [J]. Nutrients, 2019, 11(9): 2121.
15. Hu E A, Lazo M, Rosenberg S D, et al., Alcohol consumption, and incident kidney disease: results from the atherosclerosis risk in communities study [J]. Journal of Renal Nutrition, 2020, 30(1): 22–30.
16. Dunkler D, Kohl M, Teo K K, et al. Population-attributable fractions of modifiable lifestyle factors for CKD and mortality in individuals with type 2 diabetes: a cohort study [J]. American Journal of Kidney Diseases, 2016, 68(1): 29–40.
17. Roerecke M, Rehm J. Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers [J]. BMC medicine, 2014, 12(1): 1–11.
18. Hashimoto Y, Imaizumi T, Kato S et al., Effect of body mass index on the association between alcohol consumption and the development of chronic kidney disease [J]. Scientific reports, 2021, 11(1): 1–9.
19. Yuan H, Yu Q, Bai H, et al., Alcohol intake, and the risk of chronic kidney disease: results from a systematic review and dose–response meta-analysis [J]. European Journal of Clinical Nutrition, 2021, 75(11): 1555–67.
20. Li Y, Zhu B, Song N, et al., Alcohol consumption and its association with chronic kidney disease: Evidence from a 12-year China health and Nutrition Survey [J]. Nutrition, Metabolism and Cardiovascular Diseases, 2022, 32(6): 1392–401.
21. Paulson Q X, Hong J, Holcomb V, B, et al. Effects of body weight and alcohol consumption on insulin sensitivity [J]. Nutrition journal, 2010, 9(1): 1–14.
22. Fernandez-Sola J. Cardiovascular risks and benefits of moderate and heavy alcohol consumption [J]. Nature Reviews Cardiology, 2015, 12(10): 576–87.
23. Lee J-H, Kim D, Kim H J, et al., Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease [J]. Digestive and Liver Disease, 2010, 42(7): 503–8.
24. Meffert P J, Baumeister S E, Lerch M, M, et al. Development, external validation, and comparative assessment of a new diagnostic score for hepatic steatosis [J]. Official journal of the American College of Gastroenterology| ACG, 2014, 109(9): 1404–14.
25. Inker L A, Astor B C, Fox C, H, et al., KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD [J]. American Journal of Kidney Diseases, 2014, 63(5): 713–35.
26. Shah A G, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease [J]. Clinical gastroenterology and hepatology, 2009, 7(10): 1104–12.
27. McCullough K, Sharma P, Ali T et al. Measuring the population burden of chronic kidney disease: a systematic literature review of the estimated prevalence of impaired kidney function [J]. Nephrology Dialysis Transplantation, 2012, 27(5): 1812–21.
28. Loomba R, Sanyal A J. The global NAFLD epidemic [J]. Nature reviews Gastroenterology & hepatology, 2013, 10(11): 686–90.
29. Cao Y, Deng Y, Wang J, et al., The association between NAFLD and risk of chronic kidney disease: a cross-sectional study [J]. Therapeutic Advances in Chronic Disease, 2021, 12: 20406223211048649.
30. Byrne C D, Targher G. NAFLD as a driver of chronic kidney disease [J]. Journal of hepatology, 2020, 72(4): 785–801.
31. Francque S M, Van Der Graaff D, Kwanten W J. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications [J]. Journal of hepatology, 2016, 65(2): 425–43.
32. Lee Y-J, Cho S, Kim S R. Effect of alcohol consumption on kidney function: population-based cohort study [J]. Scientific reports, 2021, 11(1): 1–9.
33. Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W et al., High alcohol consumption and the risk of renal damage: a systematic review and meta-analysis [J]. QJM: An International Journal of Medicine, 2015, 108(7): 539–48.
34. Gaziano J, M, Buring J, E, Breslow J, L, et al. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction [J]. New England Journal of Medicine, 1993, 329(25): 1829–34.
35. Wakasugi M, Kazama J J, Yamamoto S, et al., A combination of healthy lifestyle factors is associated with a decreased incidence of chronic kidney disease: a population-based cohort study [J]. Hypertension research, 2013, 36(4): 328–33.
36. Muntner P, Coresh J, Smith J C, et al., Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study [J]. Kidney international, 2000, 58(1): 293–301.
37. Mukamal K, J, Jadhav P, P, D’Agostino R, B, et al., Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort [J]. Circulation, 2001, 104(12): 1367–73.
38. Drel V R, Sybirna N. Protective effects of polyphenolics in red wine on diabetes associated oxidative/nitrative stress in streptozotocin-diabetic rats [J]. Cell Biology International, 2010, 34(12): 1147–53.
39. Nakamura T, Fujiwara N, Sugaya T, et al. Effect of red wine on urinary protein, 8-hydroxydeoxyguanosine, and liver-type fatty acid–binding protein excretion in patients with diabetic nephropathy [J]. Metabolism, 2009, 58(8): 1185–90.
40. Yahfoufi N, Alsadi N, Jambi M, et al., The immunomodulatory and anti-inflammatory role of polyphenols [J]. Nutrients, 2018, 10(11): 1618.
41. Davies M J, Baer D J, Judd J T, et al., Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial [J]. Jama, 2002, 287(19): 2559–62.
42. Joosten M, Beulens J, Kersten S et al., Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: a randomised, crossover trial [J]. Diabetologia, 2008, 51(8): 1375–81.
43. Chen J, Muntner P, Hamm L L, et al., Insulin resistance, and risk of chronic kidney disease in nondiabetic US adults [J]. Journal of the American Society of Nephrology, 2003, 14(2): 469–77.
44. Kubo M, Kiyohara Y, Kato I, et al., Effect of hyperinsulinemia on renal function in a general Japanese population: the Hisayama study [J]. Kidney international, 1999, 55(6): 2450–6.
45. Estruch R, Sacanella E, Badia E, et al. Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial: effects of wine on inflammatory markers [J]. Atherosclerosis, 2004, 175(1): 117–23.
46. Burchfiel C M, Tracy R E, Chyou P-H, et al., Cardiovascular risk factors, and hyalinization of renal arterioles at autopsy: The Honolulu Heart Program [J]. Arteriosclerosis, thrombosis, and vascular biology, 1997, 17(4): 760-8.
47. Scott R, Reddy K, Husain K, et al. Dose response of ethanol on antioxidant defense system of liver, lung, and kidney in rats [J]. Pathophysiology, 2000, 7(1): 25–32.
48. Femia R, Natali A, L’Abbate A, et al., Coronary atherosclerosis, and alcohol consumption: angiographic and mortality data [J]. Arteriosclerosis, thrombosis, and vascular biology, 2006, 26(7): 1607–12.
49. Ojeda N B, Hennington B S, Williamson D, T, et al. Oxidative stress contributes to sex differences in blood pressure in adult growth-restricted offspring [J]. Hypertension, 2012, 60(1): 114–22.
50. Wang X, Desai K, Juurlink B, et al. Gender-related differences in advanced glycation endproducts, oxidative stress markers, and nitric oxide synthase in rats [J]. Kidney international, 2006, 69(2): 281–7.
51. Yi S-W, Sull J W, Linton J A, et al. Alcohol consumption and digestive cancer mortality in Koreans: the Kangwha Cohort Study [J]. Journal of epidemiology, 2010, 20(3): 204–11.
52. Chen W Y, Rosner B, Hankinson S E, et al. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk [J]. Jama, 2011, 306(17): 1884–90.
53. Liangpunsakul S, Chalasani N. What do we recommend our patients with NAFLD about alcohol use? [J]. The American journal of gastroenterology, 2012, 107(7): 976.
54. Organization W H. Prevention of cardiovascular disease: guidelines for the assessment and management of total cardiovascular risk [M]. World Health Organization, 2007.