Elsevier

Metabolism

Volume 58, Issue 8, August 2009, Pages 1185-1190
Metabolism

Effect of red wine on urinary protein, 8-hydroxydeoxyguanosine, and liver-type fatty acid–binding protein excretion in patients with diabetic nephropathy

https://doi.org/10.1016/j.metabol.2009.03.019Get rights and content

Abstract

The aim of the present study was to determine whether red or white wine affects urinary protein, 8-hydroxydeoxyguanosine (8-OHdG), and liver-type fatty acid–binding protein (L-FABP) excretion in type 2 diabetic nephropathy patients. Twenty-four type 2 diabetes mellitus patients with nephropathy were randomly allocated to drink a 118-mL (4-oz) glass of red wine (n = 12, group A) or white wine (n = 12, group B) daily for 6 months. Twelve type 2 diabetes mellitus patients with nephropathy who did not drink any wines served as control subjects (group C). Serum creatinine, 24-hour creatinine clearance, hemoglobin A1c, urinary protein, urinary 8-OHdG, and urinary L-FABP were measured before and 3 and 6 months after the start of the study. In groups A, B, and C, serum creatinine, 24-hour creatinine clearance, and hemoglobin A1c changed little during the experimental period. However, urinary protein, 8-OHdG, and L-FABP excretions were significantly decreased at 3 (P < .05) and 6 months (P < .01) compared with the baseline values in group A. In contrast, these markers changed little during the experimental period in groups B and C. Thus, these urinary markers were significantly lower in group A than in groups B and C at 3 and 6 months. These results suggest that red wine is renoprotective whereas white wine has no such effect in type 2 diabetes mellitus patients with nephropathy. The renoprotective effect of red wine may be due in part to its ability to reduce oxidative stress.

Introduction

Oxidative stress is a central pathogenic mechanism underlying ischemic heart disease, atherosclerosis, and other chronic diseases [1]. The kidney is particularly vulnerable to damage caused by reactive oxygen species, probably because of the abundance of polyunsaturated fatty acids contained in renal lipids [2]. Reactive oxygen species are involved in the pathogenesis of glomerulosclerosis and tubulointerstitial fibrosis [2]. Epidemiologic studies have suggested beneficial effects of dietary polyphenols in reducing the risk of chronic diseases by reducing oxidative stress [3]. The beneficial effects of red wine polyphenols include prevention and/or attenuation of myocardial fibrosis, reduction in aortic wall thickening, and improvement in vascular function [4].

Diabetic nephropathy is a serious microvascular complication of diabetes and one of the main causes of end-stage renal disease. Many studies have revealed that increased oxidative stress is a major pathophysiologic mechanism underlying development of diabetic nephropathy. Treatment with a polyphenolic phytoalexin present in red wine significantly attenuated renal dysfunction and oxidative stress in diabetic rats [5]. Consumption of a moderate amount of red wine may have beneficial effects toward prevention of cardiovascular disease in diabetes patients [6]. In healthy persons, red wine has more antioxidant activity than white wine by virtue of its higher content of polyphenol [7]. However, little is known about the effect of white wine on renal function.

Liver-type fatty acid–binding protein (L-FABP) of 14.4 kd is expressed in proximal tubules of the human kidney [8]. Various pathophysiologic stresses on the proximal tubules such as significant proteinuria induce up-regulation of human L-FABP gene expression, resulting in increased urinary L-FABP excretion [8]. Urinary L-FABP levels reflect the clinical progression of chronic kidney disease. Urinary 8-hydroxydeoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage [9], and its excretion is significantly correlated with the severity of tubulointerstitial lesions in patients with diabetic nephropathy [10]. The aim of the present study was to determine whether consumption of red wine or white wine affects urinary protein, 8-OHdG, and L-FABP excretion in type 2 diabetic nephropathy patients.

Section snippets

Subjects and methods

Thirty-six patients with type 2 diabetic nephropathy (23 men and 13 women; age, 55 ± 11 years) were enrolled in the study. Diagnosis was based on clinical symptoms including chronic diabetes, increased urinary albumin excretion and retinopathy, laboratory data, or histologic findings according to the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [11]. Diabetic nephropathy was defined as at least 2 of 3 measurements of the albumin-creatinine ratio done

Results

There were no adverse effects including hypoglycemia during 6 months in all subjects. Clinical and laboratory baseline data of each group are shown in Table 1. After 6 months, the intake of fruit, vegetables, fish, meat, and polyunsaturated fatty acids was similar in the 3 groups (statistically not significant). We found a similar intake of total calories between the 3 groups (A, 1660 ± 140 kcal/d; B, 1640 ± 120 kcal/d; C, 1680 ± 130 kcal/d) (statistically not significant). There were no

Discussion

In the present study, we first observed that red, but not white, wine reduced urinary protein, urinary 8-OHdG, and urinary L-FABP levels in patients with diabetic nephropathy. Previous studies of tubulointerstitial injury as well as glomerular injury in diabetes may provide additional insight into the pathogenesis of diabetic nephropathy and lead to the identification of targets for therapeutic intervention [16]. We reported previously that urinary L-FABP appears to be associated with the

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