Author: James Anderson

Alcohol Consumption Can be a Double-Edged Sword for Chronic Kidney Disease Patients PMC

Although moderate alcohol consumption contributes to increased insulin sensitivity [95,96] and delays the progression of diabetes [77,97], the prognosis of such patients differs from non-diabetic but moderate drinking patients with CKD. This indicates that moderate drinking may be beneficial for patients with CKD, but it is not enough to offset the adverse effects of metabolic disease on these patients. Both acute and chronic alcohol consumption can compromise kidney function, particularly in conjunction with established liver disease. Investigators have observed alcohol-related changes in the structure and function of the kidneys and impairment in their ability to regulate the volume and composition of fluid and electrolytes in the body.

Hepatorenal syndrome, which is secondary to alcoholic hepatitis [65], and acute kidney injury, secondary to rhabdomyolysis, also cannot be ignored [46]. Some studies found that ethanol has an influence on renal damage, such as apoptosis and epithelial mesenchymal transdifferentiation. Nesreen and Sayed discovered that alcohol consumption significantly increased renal caspase3, caspase8, and caspase9 activity, and ethanol toxicity can increase the ratios of Bax and Bcl-2 in kidney tissues compared to a control group [24,25]. This indicates that long-term ethyl alcohol consumption can activate both intrinsic and extrinsic pathways of apoptosis in the kidneys (Figure 1). However, other studies found that long-term alcohol consumption aggravates renal fibrosis, which may be related to epithelial mesenchymal transdifferentiation and fibrosis induced by ethanol [33,47,56].

Their results show not only how alcohol disrupts homeostasis but also how the body reacts to restore it. Following moderate alcohol consumption—about 24 oz—of nonalcoholic beer with 1 milliliter of alcohol per kilogram of body weight added, the investigators noted several effects. Alcohol-induced urination reduced the subjects’ plasma volume, resulting in an increased concentration of plasma sodium. In addition, the subjects’ blood pressure and plasma potassium concentration decreased. These changes in fluid volume, electrolyte balance, and blood pressure may have stimulated the activity of hormones to return body fluid volume and composition back to normal, which occurred soon after consumption.

Kidney injury secondary to alcohol hepatitis, cirrhosis, and other conditions

People older than age 50 overcome suppression of ADH more quickly than their younger counterparts do, despite reaching similar serum electrolyte concentrations after alcohol consumption. In older people, ADH levels sharply increase following alcohol intake, perhaps in part because sensitivity to increased electrolyte concentration is enhanced with age. It is not known whether chronic alcoholic patients experience a similar difference in the ADH response as they age, however.

For example, almost 30 years ago, Koppel and colleagues (1969) demonstrated that kidneys transplanted from patients with hepatorenal syndrome are capable of resuming normal function in recipients without liver disease. In addition, Iwatsuki and colleagues (1973) and Gonwa and Wilkinson (1996) documented the return of normal kidney function in hepatorenal syndrome patients who receive liver transplants. In many patients with liver cirrhosis, the kidneys’ ability to create dilute urine is compromised, leading to a state of abnormally low sodium concentration (i.e., hyponatremia). In hyponatremic patients, the amount of fluid retained by the kidneys is disproportionately greater than the amount of sodium retained. In other words, the kidneys’ ability to excrete excess fluid by way of dilute urine is impaired, and too much fluid is reabsorbed.

Moreover, other bioactivators in red wine, excluding resveratrol, and those in white wine, also have the function of ROS scavenging and renal protection [7,84,113]. NO is a free gaseous signal molecule produced by the NOS family, including neuronal NO synthase (nNOS), inducible NO synthase (iNOS), and endothelial NO synthase (eNOS), and it plays an important role in hemodynamics regulation. In general, NO is generated by mesangial cells and renal tubular epithelial cells, and it plays an important role in the regulation of glomerular and medullar hemodynamics and renin release. Although different studies have shown opposite results for the effects of NO and NOS activity with alcohol consumption [19,39,46,47], they came to a similar conclusion that NO and NOS play important roles in glomerular endothelial cell injury.

Assessment of alcohol consumption

This meta-analysis found a significant difference when comparing episodic heavy drinkers with moderate regular drinkers; the former increases the risk of ischemic heart diseases [115]. There is a lower risk of ischemic heart disease for moderate drinkers without heavy drinking occasions and a higher risk for drinkers with the same average amount who engaged in heavy episodic drinking [76]. Moreover, the harmful effect of episodic heavy drinking seems to be more obvious in people with light alcohol consumption, and it may be related to a rise in platelet reactivity and thrombosis after binge drinking [9]. This was assessed by measuring the change in the estimated glomerular filtration rate (eGFR) calculated by subtracting the baseline eGFR from the eGFR at the sixth phase of follow-up. The association of the secondary exposures—frequency of alcohol consumption and binge drinking—with the change in the eGFR were also assessed.

Ethanol administration in rats showed particular alterations in the renal antioxidant system and glutathione status [4,5]. Polyphenols, which are found in beverages, such as red wine, also have antioxidant effects [6,7]. However, another rat model showed that ethanol may increase blood pressure and angiotensin II type 1 receptor expression, causing glomerular morphology changes. This may lead to renal corpuscle and glomeruli atrophy and reduced glomeruli volume [8]. Substantial evidence exists to support the concept that kidney failure in hepatorenal syndrome is not related to structural damage and is instead functional in nature.

1. Furthermore, alcohol has an anti-inflammatory effect, with increased serum interleukin-10 levels and decreased serum interleukin-16 levels [20].
2. However, recent studies have demonstrated that its activity is decreased by ROS and lipid peroxidation with the consumption of ethyl alcohol [22,41,52].
3. Hyponatremia probably is the single most common electrolyte disturbance encountered in the management of patients with cirrhosis of the liver (Vaamonde 1996).
4. Consequently, they will develop increasing ascites and edema and experience weight gain.
5. And S.R.K. reviewed and revised the paper; all authors approved the final version of the manuscript.

Nowadays, many forms of ethyl alcohol are available, such as beer, wine, vodka, and other spirits, and these have become very popular among adults. The World Health Organization estimates that more than 55% of adults consume alcohol, and 140 million people worldwide have alcoholism [1,2]. In fact, alcoholism is a serious problem in Asia, where 10.6–23.67% of men and 1.84–5.3% of women have a history of excessive alcohol consumption [3–9].

Indirect Effects

Patients who are drinking more red wine may also benefit from its cardiovascular protective effects. Clinical studies of hypertensive patients have demonstrated that reducing alcohol intake lowers blood pressure and resuming consumption raises it. Although the mechanisms responsible for these effects have not been established, an experimental study by Chan and Sutter (1983) offers some insight. In this study, male rats given 20-percent alcohol in their drinking water for 4 weeks experienced decreased urinary volume and sodium excretion as well as increased blood concentrations of hormones that raise blood pressure by constricting blood vessels.

The amounts of these substances must be held within very narrow limits, regardless of the large variations possible in their intake or loss. The kidneys are the organs primarily responsible for regulating the amounts and concentrations of these substances in the extracellular fluid. You probably know someone who developed health problems from drinking too much alcohol.

Although studies on individual differences in alcohol consumption and CKD are limited, existing studies have found that individual variation in an alcohol dehydrogenase gene may play a role [98], but more studies are needed to confirm these findings. Subjects that were aged more than 18 years old were selected from the 2001, 2005, and 2009 NHIS. Those with a diagnosis of CKD in the medical insurance record before the interview date were excluded. The follow-up duration began since the interview date and censored on the date of incident CKD, death, or Dec 31, 2013, which ever come first.

Ethanol and polyphenol both have anti-oxidative effects and ethanol improves polyphenol absorption, thereby contributing to bioavailability [4,5,6]. Furthermore, alcohol has an anti-inflammatory effect, with increased serum interleukin-10 levels and decreased serum interleukin-16 levels [20]. Alcohol consumption can raise high-density lipoprotein cholesterol concentration [21,22], improve insulin sensitivity [23], and reduce platelet aggregation rate and fibrinolysis [21,22]. Alcohol consumption, including vodka and red wine, also reduced serum insulin concentrations and enhanced the insulin sensitivity index [24,25]. A moderate amount of alcohol drinking decreases the risk of developing diabetes, showing a U-shaped association [26]. As an example, Puddey and colleagues (1985) evaluated the effects of hormones that regulate kidney function.

If an acute alcoholic binge induces extensive vomiting, potentially severe alkalosis may result from losses of fluid, salt, and stomach acid. Studies historically have shown that alcohol consumption markedly increases magnesium excretion in the urine and may affect magnesium levels in other ways as well. For example, when rats are given alcohol, they also require significant magnesium in their diets, suggesting that alcohol disrupts absorption of this nutrient from the gut. Investigators have speculated that alcohol or an intermediate metabolite directly affects magnesium exchange in the kidney tubules (Epstein 1992).

In addition, Das et al. reported that alcohol consumption impairs the ability of CAT to catalyze the decomposition of H2O2 in the kidneys [41]. This subsequently promotes the conversion of H2O2 to the more reactive hydroxyl radicals, which cause damage in antioxidant capacities and mitochondria in renal cells [34,42,43]. Samadi et al. also suggested that ethanol induces depression of nephrin and podocin in podocytes, which contributes to renal injury and proteinuria and is mediated by oxidative stress [44]. Physically, the kidneys have several enzymes with antioxidant capacities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase, which can balance various oxidative processes. Several studies have demonstrated that alcohol consumption increases ROS generation, which contributes to lipid peroxidation and damages antioxidant capacity [34,35].