Relation Of Alcohol Intake To Kidney Function And Mortality Observational, Population-Based, Cohort Study

4. Discussion

The results of the present long-term observational study indicate that, in an Italian sample of the general population with adult age, a higher habitual alcohol intake relates cross-sectionally to a higher eGFR and longitudinally to a less negative long-term eGFR change over time independently of gender, age, and several other variables. Moreover, the study reports the novel observation that moderate alcohol intake in the range of 1–24 g/day is also associated with reduced mortality in the individuals with decreased eGFR.

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NEW HERS LIQOUR FOR DECREASED EGFR

The main limitation of the study includes the fact that data collection was not recent. However, the importance of this limitation is reduced by the consistency of the findings in three separate exams performed over a 20-year observation period from 1983–85 (Exam-1) to 2001–07 (Exam-3). Another limitation is the fact that the study did not collect complete information on the habitual diet composition but only data about the dietary intake of sodium, potassium, and protein. However, only 2 of the 14 previous studies on alcohol and kidney function reported data about diet composition [3–16]. The confounding should have been minor for examinees dead during follow-up or lost to follow-up because the differences in alcohol intake were minor and inconsistent in comparisons to examinees with complete data at all exams. The last limitation could be the fact that the study can give information on alcohol intake in the form of wine but not of other beverages, given that wine accounted for more than 94% of total alcohol intake at all exams in the Gubbio population. This peculiarity was expected in an Italian population sample [21,22] and could also be considered a merit of the study because the homogeneity of the drinking patterns of the Gubbio cohort implies a lower confounding effect due to differences between wine and other beverages. The merits of this study are the use of updated methods for accurate eGFR calculation, the analyses of datasets from three separate exams, the analyses of erythrocytic mean corpuscular cell volume and serum gamma-glutamyl transpeptidase as objective markers of alcohol intake, and the inclusion in analyses of mortality as a potential determinant of selection-bias due to alcohol-related mortality [40]. 

As for the inconsistency of the findings between the present study and the previous studies, alcohol intake did not associate with the change of kidney function over time in five studies (3–8). Important methodological differences could explain the lack of significant associations in those previous studies. Two of them were based on eGFR calculation with low accuracy in the normal range of kidney function (3,4); three studies did not focus on eGFR change but only on the incidence of eGFR <60 mL/min × 1.73 [5,7,8]; two studies included the elderly only [6,7]. In contrast with the present results, two studies reported detrimental effects of alcohol intake on kidney function [9,10]. However, they could not be considered relevant to the present study because they investigated only heavy alcohol drinking and alcohol abuse or alcohol dependence [9,10]. The remaining studies on alcohol and kidney function reported favorable effects of alcohol intake on kidney function in accordance with the present results [11–17].

The mechanisms remain hypothetical for the relationship of higher alcohol intake in the form of wine with higher eGFR and less negative eGFR change over time. Theoretically, alcohol in the form of wine could positively affect kidney function due to its content of polyphenols [41], via the inhibition of antidiuretic hormone secretion [42,43], or via its effects on the endothelium [44]. Other mechanisms cannot be excluded. 

Regarding practical implications, this study supports the idea that there is no need to forbid the intake of wine in people with or at risk of low kidney function. This idea is further supported by the evidence that an alcohol intake of 1–24 g/day, corresponding to an intake of wine up to two glasses per day, is associated with a 23% reduced mortality rate in keeping with the so-called "French paradox" [45]. The possibility that this finding reflected only higher mortality in the stratum with no alcohol intake could not be excluded because the results were not consistent in the subgroup analysis excluding examinees who moved to the stratum with no alcohol intake only after Exam-2. In this light, two useful novel observations were reported by the present study: first, the reduction in mortality rate associated with moderate wine intake was detectable also in individuals with decreased eGFR; second, higher wine intake was associated cross-sectionally and longitudinally with better kidney function but not with increased mortality risk. 

5. Conclusions

Briefly, this observational cohort study reports that, in an Italian sample of the adult general population, independent of gender, age, and several other variables, a higher alcohol intake in the form of wine was related cross-sectionally to a higher eGFR and  longitudinally to a lesser eGFR decline during an observation period ranging from 6 to 20 years. Altogether, these results support the hypothesis that the intake of wine could have favorable effects against the decline in kidney function associated with ageing without implying an increased rate of mortality 

Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu14061297/s1, Table S1-Italian standards of volume, alcoholic graduation, alcohol equivalents of alcohol-containing servings. Table S2-Simple correlation coefficient of covariates with alcohol intake in 2069 adult examinees with complete data at Exam-1, Exam-2, and Exam-3. Table S3-Systolic pressure, diastolic pressure, and antihypertensive drug treatment by exam and stratum of alcohol intake in 2069 adult examinees with complete data at Exam-1, Exam-2, and Exam-3. Table S4-Descriptive statistics at Exam-1 in examinees participating in all exams, in examinees dead during follow-up, and in examinees not dead and lost to follow-up. Table S5-Cross-sectional analyses: multi-variable linear regression models for data of Exam-1 with eGFR regressed over stratum of alcohol intake and covariates in examinees that did not take part in Exam-2 and/or Exam-3. Table S6-Cross-sectional analyses: multi-variable linear regression models with eGFR regressed over alcohol intake and covariates at Exam-1, Exam-2, and Exam-3. Table S7-Longitudinal analyses: multi-variable linear regression models with annualized eGFR change and eGFR slope regressed over alcohol intake and covariates. 

Author Contributions: The Gubbio study was conducted by the Centro Studi Epidemiologici di Gubbio in collaboration with the Gubbio Hospital, the University of Naples Federico II, the University of Milan, the Northwestern University of Chicago, and the Istituto Superiore di Sanità. The present analysis was planned by M.C. The first draft of the manuscript was prepared by M.C. and M.L. took responsibility for the overall content of the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. G.B., C.S., G.I., C.F., and O.T.-V. contributed to the acquisition and the analysis of data. All authors provided substantial contributions to the following: acquisition, analysis, or interpretation of data; drafting the manuscript or revising it critically for important intellectual content; final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript. 

Funding: In the past: economic support to the Gubbio study was provided by Merck, Sharp, and Dohme, Italy; the US National Heart, Lung, and Blood Institute (grant R01HL-40397-02) and the Ministero Italiano di Università e Ricerca (grant 068034, PRIN 2004). None of the sponsors or funders had any role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Institutional Review Board Statement: The study adheres to the Declaration of Helsinki and received approval by the local institutional committee (CEAS-Umbria #2850/16). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. 

Data Availability Statement: Data are stored in the Gubbio study repository. For information, write to mlaurenzi@comcast.net. 

Acknowledgments: The Gubbio Study was made possible thanks to the enthusiasm of the people of the town of Gubbio and the support of its municipal and health authorities and community leaders. 

Conflicts of Interest: The authors declare no conflict of interest. 

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