Relation of Alcohol Intake to Kidney Function and Mortality Observational, Population-Based, Cohort Study

Abstract

Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1−24, 25−48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1−24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.

Keywords: alcohol; eGFR; epidemiology; mortality; wine.

Figure 1

Examinees participating in each exam, examinees lost to follow-up, and dead examinees.

Figure 2

Skewness and frequency distribution of alcohol intake (g/d = g/day) at Exam-1 (black bars), Exam-2 (grey bars), and Exam-3 (white bars) in the 2069 examinees with complete data at all exams.

Figure 3

Mean and 95%CI of erythrocytic mean corpuscular volume by stratum of alcohol intake (g/d = g/day) at Exam-1, Exam-2, and Exam-3. Number of examinees per stratum is reported in Table 1. p-values are from non-adjusted ANOVA.

Figure 4

Mean and 95%CI of serum gamma-glutamyl transpeptidase by stratum of alcohol intake (g/d = g/day) at Exam-2. Number of examinees per stratum is reported in Table 1. p-value is from non-adjusted ANOVA.

Figure 5

Cross-sectional analyses: mean and 95%CI of eGFR by stratum of alcohol intake (g/d = g/day) at Exam-1, Exam-2, and Exam-3 in non-adjusted ANOVA (black lines) and ANOVA adjusted for covariates (grey lines). Number of examinees per stratum is in Table 1. p-values are from ANOVA. Covariates in adjusted ANOVA for Exam-1 data: gender and data at Exam-1 for age, education, log-transformed urinary sodium/creatinine ratio, log-transformed urinary potassium/creatinine ratio, urinary creatinine, body mass index, systolic pressure, diastolic pressure, antihypertensive drug treatment, serum total cholesterol, smoking, and diabetes. Covariates in adjusted ANOVA for Exam-2 data: gender and data at Exam-2 for age, education, log-transformed urinary sodium/creatinine ratio, log-transformed urinary potassium/creatinine ratio, log-transformed urinary urea nitrogen/creatinine ratio, urinary creatinine, body mass index, systolic pressure, diastolic pressure, antihypertensive drug treatment, serum total cholesterol, smoking, and diabetes. Covariates in adjusted ANOVA for Exam-3 data: gender and data at Exam-3 for age, education, urinary creatinine, body mass index, systolic pressure, diastolic pressure, antihypertensive drug treatment, serum total cholesterol, smoking, and diabetes.

Figure 6

Longitudinal analyses: mean and 95%CI of annualized eGFR change from Exam-1 to Exam-2 by stratum of alcohol intake (g/d = g/day) at Exam-1, of annualized eGFR change from Exam-2 to Exam-3 by stratum of alcohol intake at Exam-2, and of eGFR slope over time from Exam-1 to Exam-3 by stratum of mean alcohol intake during follow-up in non-adjusted ANOVA (black lines) and in ANOVA adjusted for covariates (grey lines). p-values are from ANOVA. Number of examinees per alcohol stratum is in Table 1 for eGFR change from Exam-1 to Exam2 and for eGFR change from Exam-2 to Exam3. Number of examinees per alcohol stratum for eGFR slope is as follows: 0 g/day = 331, 1–24 g/day = 1146, 25–48 g/day = 331, and > 48 g/day = 261. Covariates in adjusted ANOVA on eGFR change from Exam-1 to Exam-2: gender and data at Exam-1 for age, eGFR, education, log-transformed urinary sodium/creatinine ratio, log-transformed urinary potassium/creatinine ratio, urinary creatinine, body mass index, systolic pressure, diastolic pressure, antihypertensive drug treatment, serum total cholesterol, smoking, and diabetes. Covariates in adjusted ANOVA on eGFR change from Exam-2 to Exam-3: gender and data at Exam-2 for age, eGFR, education, log-transformed urinary sodium/creatinine ratio, log-transformed urinary potassium/creatinine ratio, log-transformed urinary urea nitrogen/creatinine ratio, urinary creatinine, body mass index, systolic pressure, diastolic pressure, antihypertensive drug treatment, serum total cholesterol, smoking, and diabetes. Covariates in adjusted ANOVA on eGFR slope over time from Exam-1 to Exam-3: gender, data at Exam-1 for age, eGFR, antihypertensive drug treatment, smoking, and diabetes, and means of data available from Exam-1 to Exam-3 for education, log-transformed urinary sodium/creatinine ratio (not measured at Exam-3), log-transformed urinary potassium/creatinine ratio (not measured at Exam-3), log-transformed urinary urea nitrogen/creatinine ratio (measured at Exam-2 only), urinary creatinine, body mass index, systolic pressure, diastolic pressure, and serum total cholesterol.