Alcohol’s Impact on Kidney Function (2024)

Kidney Structure and Function

Cushioned in fatty tissue near the base of the spinal column, the kidneys are efficiently designed organs that perform two primary tasks in the body: excretion of metabolic end products and precise regulation of body fluid constituents. As they accomplish these tasks, the kidneys form and collect urine, which exits through the ureters to the bladder.

Each of the 2 million functional units (i.e., nephrons) in a pair of normal kidneys forms urine as it filters blood plasma of substances not needed by the body. Within each nephron, blood plasma enters a tiny ball of unusually permeable capillaries (i.e., the glomerulus), filters into a capsule that surrounds the glomerulus, then flows through a long, looping conduit called the nephron tubule.

As the plasma filtrate passes along this channel, the substances the body needs to conserve are reabsorbed into an extensive network of capillaries that wrap the nephron tubule. Many electrolytes and 99 percent of the water in the filtrate are reabsorbed, while waste products, such as urea (an end product of protein metabolism formed chiefly in the liver) and creatinine (an end product of muscle metabolism), as well as excess electrolytes (particularly sodium, potassium, chloride, and hydrogen ions), continue to journey along the tubule. Small amounts of unwanted substances also are secreted directly into the nephron tubules. Together, the filtered and secreted substances form urine (see figure) and eventually trickle into a series of progressively larger collecting ducts. Each 4.5-inch-long kidney contains about 250 of the largest collecting ducts, each duct transmitting urine from approximately 4,000 nephrons.

Of the 48 gallons of filtrate processed through the nephrons of the kidneys each day, only about 1 to 1.5 quarts exit as urine. During this filtering process, substances are reabsorbed or secreted to varying degrees as the filtrate passes through the distinct segments of the nephron tubule.

Regulating Electrolyte Levels and Fluid Volume

The kidney tubules play an important role in keeping the body’s water and electrolyte levels in equilibrium. In many cases, control mechanisms govern the rate of reabsorption or secretion in response to the body’s fluctuating needs (see table for a summary of the body processes influenced by key electrolytes). Under the influence of antidiuretic hormone (ADH), for example, the tubules can create either a concentrated urine, to discharge excess solutes and conserve water, or a dilute urine, to remove extra water from body fluids. In the first case, when body fluids become too concentrated with solutes, the pituitary gland produces abundant ADH, which induces the kidneys to conserve water and concentrate urine, an important ability that enables thriving in an environment where water may be scarce. In the absence of ADH, when body fluids are overly dilute, the kidneys dilute the urine, allowing more water to leave the body. “Normal” urine flow rate is 1 milliliter per minute (i.e., approximately 1 to 1.5 L/day), but this rate can vary widely, depending on water intake or dehydration level, for instance.

The kidneys continuously perform their tasks of purifying and balancing the constituents of the body’s fluids. Although resilient, the kidneys can deteriorate as a result of malnutrition, alcohol abuse or dependence, or liver and other diseases. Healthy kidneys are vital to the function of all the body’s organs and systems.

— Mary Beth de Ribeaux

Mary Beth de Ribeaux is a science editor of Alcohol Health & Research World

Fluid

Alcohol can produce urine flow within 20 minutes of consumption; as a result of urinary fluid losses, the concentration of electrolytes in blood serum increases. These changes can be profound in chronic alcoholic patients, who may demonstrate clinical evidence of dehydration.

As most investigators now agree, increased urine flow results from alcohol’s acute inhibition of the release of antidiuretic hormone (ADH), a hormone also known as vasopressin, which normally promotes the formation of concentrated urine by inducing the kidneys to conserve fluids. In the absence of ADH, segments of the kidney’s tubule system become impermeable to water, thus preventing it from being reabsorbed into the body. Under these conditions, the urine formed is dilute and electrolyte concentration in the blood simultaneously rises. Although increased serum electrolyte concentration normally activates secretion of ADH so that fluid balance can be restored, a rising blood alcohol level disrupts this regulatory response by suppressing ADH secretion into the blood.

Interestingly, age makes a difference in how rapidly the body escapes alcohol’s ADH-suppressive effect. 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.

Sodium

The serum sodium level is determined by the balance of fluid in relation to that of sodium: Not enough fluid in the body results in a sodium concentration that is too high (i.e., hypernatremia), whereas excessive amounts of fluid produce a sodium concentration that is too low (i.e., hyponatremia). Hyponatremia does not constitute merely a biochemical abnormality but most likely has clinical consequences as well (e.g., impaired mental activity, neurological symptoms, and, in extreme instances, seizures).

“Beer drinkers’ hyponatremia” is a syndrome that appears to result from an intake of excessive fluid in the form of beer. Hilden and Svendsen (1975) observed hyponatremia in five patients who drank at least 5 liters of beer per day (L/d) without any other nourishment. (For comparison, a person’s normal fluid intake averages a little more than 2 L/d.) Because beer contains few dissolved substances (i.e., solutes), such as sodium, these patients apparently lacked a sufficient quantity of solutes to stimulate the kidneys to eliminate excess fluid.

Although fluid overload—not alcohol itself—is considered the major contributor to beer drinkers’ hyponatremia, alcohol does appear to directly influence the kidney’s handling of sodium and other electrolytes, potentially resulting in hypernatremia. In a study by Rubini and colleagues (1955), subjects who consistently drank about 4 ounces (oz) of 100-proof bourbon whiskey experienced decreased sodium, potassium, and chloride excretion (i.e., increased retention of solutes). Although some exceptions exist, several historical studies have reported similar modest reductions in sodium and potassium excretion following alcohol use.

In general, however, neither acute nor chronic alcohol consumption directly causes significant changes in serum sodium concentrations, although impaired sodium excretion is a frequent complication of advanced liver disease, as discussed later in this article.

Potassium

Normally the kidneys are a major route of potassium ion excretion and serve as an important site of potassium regulation. Alcohol consumption historically has been found to reduce the amount of potassium excreted by the kidneys (e.g., Rubini et al. 1955), although the body’s hydration state may help determine whether potassium excretion will increase or decrease in response to alcohol. Levels of potassium, like those of sodium, also can affect the way the kidneys handle fluid elimination or retention. In addition, potassium depletion has been proposed to exacerbate hyponatremia through any of several mechanisms (Epstein 1992): For example, potassium losses may stimulate ADH activity, thereby increasing the amount of fluid reabsorbed and causing the body’s sodium concentration to decrease as a result. Alternatively, potassium losses may increase thirst, also through hormonal mechanisms, thereby promoting increased fluid intake.

Phosphate

Low blood levels of phosphate commonly occur acutely in hospitalized alcoholic patients, appearing in more than one-half of severe alcoholism cases. Indeed, when the condition does not appear, clinicians treating alcoholic patients should suspect that another problem is masking the recognition of low phosphate levels, such as ongoing muscle dissolution, excess blood acidity (i.e., acidosis), inadequate blood volume, or kidney failure.

Several mechanisms may contribute to abnormally low phosphate levels (i.e., hypophosphatemia) (see box). Simply lacking an adequate amount of phosphate in the diet is one possible reason for phosphate deficiency. For severely alcoholic patients who eat poorly, such a nutritional deficit may be an important contributor to hypophosphatemia.

Another potential cause of hypophosphatemia in alcoholic patients is hyperventilation, which can occur during alcohol withdrawal. Prolonged rapid, shallow breathing results in excessive loss of carbon dioxide and decreased blood acidity (i.e., alkalosis), which in turn activates an enzyme that enhances glucose breakdown. In glucose breakdown, phosphate becomes incorporated into various metabolic compounds, ultimately lowering blood levels of phosphate. As the rate of glucose breakdown increases, profound hypophosphatemia potentially can result.

Insulin administration also can lead to mild hypophosphatemia, because it decreases cellular acidity. Although insulin more likely plays a contributory, rather than principal, role in producing hypophosphatemia in alcoholic patients, there are clinical implications to consider. Both glucose and amino acids are powerful triggers for insulin release, and hospitalized alcoholic patients frequently receive intravenous fluids containing these nutrients. Physicians thus should be prepared to respond if hypophosphatemia develops. A similar concern applies to another treatment that may lead to hypophosphatemia: overfeeding patients beyond normal nutrient requirements in an attempt to replace dietary deficiencies.

Alcoholic patients also may develop low blood levels of phosphate by excreting too much of this ion into their urine. Typically, chronic alcoholic patients are losing up to 1.5 g/d of phosphate through their urine when they have reached the point of being sick enough to accept hospitalization. (For comparison, a normal healthy person excretes 0.7 to 0.8 g/d.) Over the next several days of hospitalization, these patients often excrete virtually no phosphate in their urine; simultaneously, their blood phosphate levels dip to low levels before returning to normal. The combination of low phosphate excretion and low blood levels indicates that phosphate is simply being shifted from the bloodstream into body cells, implying that kidney dysfunction is not a likely cause of phosphate wasting in this case.

Alcohol can induce abnormally high phosphate levels (i.e., hyperphosphatemia) as well as abnormally low levels. In fact, hyperphosphatemia often precedes hypophosphatemia. Alcohol consumption apparently leads to excessive phosphate levels by altering muscle cell integrity and causing the muscle cells to release phosphate. This transfer of phosphate out of muscle cells and into the bloodstream results in an increased amount of phosphate passing through the kidneys’ filtering system. In response, reabsorption of phosphate diminishes and excretion in urine increases in an effort to return blood levels of this ion to normal.

Magnesium

Chronic alcoholism is the leading cause of low blood levels of magnesium (i.e., hypomagnesemia) in the United States (Epstein 1992). Often it occurs simultaneously with phosphate deficiencies, also frequently encountered among alcoholic patients. Hypomagnesemia responds readily to magnesium supplementation treatment, however.

Several alcohol-related mechanisms can result in hypomagnesemia. 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).

Calcium

Early studies showed that alcohol consumption markedly increases calcium loss in urine. In severely ill alcoholic patients, low blood levels of calcium occur about as often as low blood levels of phosphate and can cause convulsions or potentially life-threatening muscle spasms when respiratory muscles are involved. Alcoholic patients with liver disease often have abnormally low levels of a calcium-binding protein, albumin, and also may have impaired vitamin D metabolism; either of these two factors could result in reduced blood levels of calcium (i.e., hypocalcemia). Muscle breakdown and magnesium deficiency are other potential causes of hypocalcemia in alcoholic patients. A direct effect of alcohol in reducing calcium levels is suggested by at least one experimental study: Dogs became hypocalcemic after administration of alcohol above a critical threshold amount of approximately 1 g/kg (Money et al. 1989).

Impaired Sodium Handling

Patients with alcohol-induced liver cirrhosis show a great tendency to retain salt (i.e., sodium chloride), and their urine frequently is virtually free of sodium. A progressive accumulation of extracellular fluid results, and this excess fluid is sequestered primarily in the abdominal region, where it manifests as marked swelling (i.e., ascites) (see figure). In addition, excess fluid accumulates in spaces between cells, clinically manifested as swelling (i.e., edema) of the lower back and legs. As long as cirrhotic patients remain unable to excrete sodium, they will continue to retain the sodium they consume in their diet. Consequently, they will develop increasing ascites and edema and experience weight gain. In some cases, vast amounts of abdominal fluid may collect, occasionally more than 7 gallons (Epstein 1996).

Rigorously limiting sodium intake, which is the first step in treating ascites, will halt fluid retention. Such sodium restriction alone may bring about a spontaneous increase in urine flow and relieve ascites, but how often this response occurs and in which patients is unknown and unpredictable. Other treatment options include various diuretic agents and, when ascites stubbornly persists, aspiration of the excess abdominal fluid. Many sodium-retaining patients who receive large quantities of sodium-free water can excrete copious amounts of dilute urine, thus demonstrating that the main kidney dysfunction associated with their ascites is an impaired ability to excrete sodium, not water.

The events leading to abnormal sodium handling in patients with cirrhosis are complex and controversial, however. Investigators have advanced several theories suggesting the involvement of a constellation of hormonal, neural, and hemodynamic mechanisms (Epstein 1996; Laffi et al. 1996). The traditional hypothesis holds that the kidneys of cirrhotic patients retain sodium in response to ascites that develops when liver dysfunction causes blood vessels to expand beyond available plasma volume (i.e., the “underfill” theory). In contrast, the “overflow” theory postulates that ascites follows when the kidneys retain sodium in response to signals sent by a dysfunctional liver to expand plasma volume. The answer to this version of the “chicken-and-egg” question remains to be elucidated.

Impaired Fluid Handling

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. Hyponatremia probably is the single most common electrolyte disturbance encountered in the management of patients with cirrhosis of the liver (Vaamonde 1996). This abnormality may reflect the severity of liver disease, but the available data do not allow correlation of kidney impairment with the degree of clinical signs of liver disease, such as ascites or jaundice.

A compromised diluting ability has important implications for the management of patients with advanced liver disease. Restricting the fluid intake of hyponatremic patients eventually should restore a normal fluid balance; unfortunately, this restriction may be difficult to implement. Patients frequently fail to comply with their physician’s orders to limit their fluid intake. Furthermore, clinicians sometimes overlook the fact that fluids taken with medications also must be restricted for these patients and mistakenly bring pitchers of juice or water to their bedsides.

The difficulties in successfully managing dilutional hyponatremia have resulted in the recent emergence of a promising class of new drugs to treat this abnormality. Specifically, drugs known as arginine vasopressin antagonists are being developed to inhibit ADH at the cell receptor level. These new drugs should dramatically facilitate treatment of cirrhotic patients with impaired fluid handling.

Hepatorenal Syndrome

Hepatorenal syndrome may appear in patients afflicted with any severe liver disease, but in the United States, studies most often have identified alcoholic cirrhosis as the underlying disorder. Major clinical features of hepatorenal syndrome include a marked decrease in urine flow, almost no sodium excretion and, usually, hyponatremia and ascites. Blood urea nitrogen (BUN) levels and serum concentrations of the waste product creatinine are somewhat elevated, but rarely to the degree seen in patients with end-stage kidney failure when kidney disease is the primary disorder. Judgments based on such relatively modest BUN and serum creatinine increases often underestimate kidney dysfunction in patients with hepatorenal syndrome, however, because malnourished cirrhotic patients tend to have low levels of urea and creatinine.

Although hepatorenal syndrome often ensues after an event that reduces blood volume (e.g., gastrointestinal bleeding), it also can occur without any apparent precipitating factor. Some observers have noted that patients with cirrhosis frequently develop hepatorenal syndrome following hospital admission, possibly indicating that a hospital-related event can trigger the syndrome. Regardless of the precipitating factor, patients who develop kidney failure in the course of alcoholic cirrhosis have a grave prognosis.

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. 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.

Indeed, liver transplantation is one of two options available today for treating hepatorenal syndrome. Gonwa and Wilkinson (1996) reported a 4-year survival rate of 60 percent in hepatorenal syndrome patients who received a liver transplant, which constitutes a major step forward, considering the previous uniformly fatal course of the disease.

Another current treatment option is known as transjugular intrahepatic portosystemic shunt (TIPS), in which a bypass (i.e., shunt) between two veins inside the liver (i.e., the hepatic vein and the portal vein) is created by way of the jugular vein. Obstructions in the liver of cirrhotic patients increase pressure in the portal vein, and this effect is thought to contribute to many kidney complications. The TIPS technique was developed as a means to reduce pressure in the portal circuit and offers several advantages: Because the shunt can be inserted under local anesthesia, TIPS avoids postoperative complications associated with surgery. In addition, TIPS does not alter the anatomy of the blood vessels outside the liver, an important consideration for potential liver-transplant candidates. The less invasive nature of TIPS makes it an attractive option for treating hepatorenal syndrome, and preliminary results show that the procedure is effective (Somberg 1996). Currently, a clinical trial sponsored by the National Institutes of Health is investigating the effects of TIPS on the treatment of ascites and improvement of kidney function.

¹For a definition of this and other technical terms used in this article, see the glossary, pp. 93–96, and the sidebar, pp. 91–92.

²The terms “alcoholic patient” and “alcoholism” as used in this article are summary terms for the diagnoses of alcohol abuse and alcohol dependence as defined variously by the studies cited.

³For a person weighing 150 pounds, this dose would be roughly equivalent to 17 drinks.

Editorial Note

The reference list accompanying this article has been shortened. A complete bibliography is available on request.

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