Dataset Information

Serum Gamma-Glutamyltransferase, Daily Alcohol Consumption, and the Risk of Chronic Kidney Disease: The Kansai Healthcare Study.

ABSTRACT:

Background

Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR).

Methods

We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ?1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m².

Results

During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (?71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (?25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (?58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR.

Conclusion

In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

SUBMITTER: Shibata M

PROVIDER: S-EPMC7064553 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Project description:Chronic and binge ethanol consumption in humans and in animal models has been associated with the induction of injury (such as fibrosis and scarring) in the liver as well as the intestine, brain, lung and immune system. The effects of chronic ethanol consumption on the human kidney are protective as seen in large population studies are controversial with the preponderance of the data suggesting protection less so than injury. The most recent meta-analysis was by Konig et al (2015) who studied 5476 participants aged 28–75 years from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study to assess associations between alcohol consumption and risk of chronic kidney disease (CKD). They found in this population-based cohort, alcohol consumption was inversely associated with the risk of developing CKD. The protective effects of ethanol on the kidney present a unique model system to develop new hypothesis on protection against end organ damage by fibrosis. The data on the effects of alcohol or alcohol consumption at the molecular level on renal parenchyma are sparse. In cell culture and animal models chronic ethanol exposure has been show to induce protein post-translational modification (acetylation), protein expression (upregulation of cytochrome P450 CYP2E1 and local platelet-activating factor receptor (PAFR) ligand formation) as well as neutrophil infiltration and activation. Since hepatocytes do not express PAFR, these data suggest that the response of the kidney to chronic alcohol consumption is distinct from that of the liver or lung. Therefore, we hypothesized that mechanisms of ethanol-induced renal injury or protection are regulated by a protein signaling networks (PSN) modulated acutely by the phosphoproteome and long term epigenetically by the acetylproteome. To address this hypothesis we have initiated a tiered proteomics study to determine the effects of chronic alcohol consumption on the murine kidney and with a secondary insult of acute exposure of lipopolysaccharide (LPS) on the renal proteome, phosphoproteome and the acetylproteome. Data have already been collected on the total proteome and the phosphoproteome using a multiplexing approach. Data will be collected early spring on the acetylproteome.