Substance Misuse and the Kidneys: Effects of Drugs on the Kidneys

The Function of the Kidneys and Renal System

The kidneys, which are part of the renal system, filter blood to remove waste and excess water via myriad filtering units called nephrons, each of which has a glomerulus and a tubule. The glomerulus filters the blood, and the tubule removes waste and returns needed substances to the blood. Ultimately, the kidneys create urine, which then passes into tubes known as ureters and flows to the bladder, where it’s stored and later expelled through the urethra.¹

Along with removing waste, kidneys produce hormones that impact various physiological processes, such as blood pressure regulation, calcium metabolism, red blood cell production, etc.² Plus, the kidneys eliminate acid and maintain a proper balance of water, salts, and critical minerals (e.g., sodium, calcium, potassium, and phosphorus). If these minerals become unbalanced, muscles, nerves, and various tissues may not function properly.¹

Given the important role the renal system plays in multiple body functions, kidney and/or renal system damage can lead to numerous diseases, including everything from mild fluid imbalances to acute kidney failure and even death.² Unfortunately, millions of people are impacted by renal diseases. In fact, according to the Centers for Disease Control and Prevention (CDC), 6 million people aged 18 and older have been diagnosed with kidney disease.³

How Drugs Cause Renal and Kidney Damage

Several factors can increase the risk of kidney damage, and with each additional factor, the risk of acute urinary system failure increases. Risk factors include underlying renal insufficiency, intravascular volume depletion (sometimes seen in people on strong diuretics, as well as those with poor oral fluid intake, gastroenteritis, or chronic diarrhea), diabetes, heart failure, being 60 years of age or older, exposure to multiple nephrotoxins, etc.⁴

Various types of drugs have the potential to be nephrotoxic. Alcohol and other substances—including cocaine, opioids, 3,4-methylenedioxymethamphetamine (aka MDMA or ecstasy)—can have direct and/or indirect physiological effects that can negatively impact kidney functioning. Examples of some of these pathological mechanisms as well as the kidney conditions they may lead to include:^2,5-9

• Vasoconstriction (i.e., narrowing of blood vessels).
• Renal cell damage from oxidative stress.
• Acute kidney injury.
• Chronic kidney disease.
• End-stage renal disease.
• Acid, fluid, and electrolyte disorders.
• Changes in kidney size and structure.
• Hepatorenal syndrome (HRS), a type of acute renal dysfunction.

Additionally, a condition known as rhabdomyolysis is also associated with several types of substance use, including cocaine, heroin, ketamine, methadone, and methamphetamine.⁴ Characterized by a breakdown of damaged muscle, which then leads to the release of muscle cell contents into the blood, rhabdomyolysis can result in kidney damage and failure, irregular heart rhythms, seizures, death, and more.¹⁰ In up to 81% of rhabdomyolysis cases, drugs and alcohol are causative factors, and among those with the condition, up to 50% eventually develop acute renal failure.⁴

As with various other health complications of drug and alcohol misuse, additional factors occurring alongside substance use can impact kidney function. That is, it can be difficult to pinpoint a specific drug as the sole cause of the renal condition. Still, research has shown associations between substance misuse and renal function. Thus, the following content offers a broad overview of several substances linked to kidney disease along with some of the more prominent conditions associated with their respective use.

Impact of Alcohol on the Kidneys

While chronic alcohol consumption is clearly a risk factor for various types of tissue injury, the various potential mechanisms by which alcohol damages the kidneys aren’t entirely understood. Plus, complex interactions between multiple organs can complicate attempts to pinpoint a precise disease mechanism. For example, some kidney conditions are actually preceded by liver diseases related to alcohol, so while alcohol is at the root of the condition, liver disease precedes renal disease. A similar relationship exists between alcohol-related heart damage, as heavy drinking is associated with cardiomyopathy and an increased risk of cardiac death. This alcohol-related heart failure, then, can also lead to kidney dysfunction.¹¹

Despite the aforementioned complexity, the following kidney and renal conditions are associated with alcohol misuse:^2,9,11-13

• Fluid imbalance and electrolyte disorders. Excessive alcohol misuse can impair the kidneys’ ability to maintain proper balances of fluids, electrolytes, and acid. This imbalance, then, can be a precursor to issues with multiple body systems. For example, chronic alcohol misuse can lead to the accumulation of fluids and solutes (e.g., electrolytes), which increase overall body fluid volume. This in turn can contribute to high blood pressure.
• Organ alterations. Animal studies indicate that alcohol can directly affect the kidneys by altering their structure and form. For example, in patients with alcohol-related liver cirrhosis, healthcare professionals have witnessed kidney enlargement of up to 33%, which is in direct proportion to patients’ liver enlargement. Drinking is also associated with the formation and accumulation of toxic metabolites (i.e., fatty acid ethyl esters) that can lead to alcohol-induced organ damage. While one study revealed that the highest levels of these metabolites were found in the heart, they also accumulated in the kidney, brain, and liver.
• Hepatorenal syndrome. Hepatorenal syndrome (HRS) is a type of acute renal dysfunction in patients that also have advanced liver disease. It results from multiple factors such as changes in blood flow, activation of vasoconstrictor systems, and reduced kidney function. If not treated properly, HRS can lead to kidney failure.
• Impaired kidney metabolism. While the liver does most of the work to metabolize alcohol, the kidneys are also involved in alcohol metabolism and excretion. Thus, excessive alcohol consumption strains kidney metabolism and can lead to oxidative stress in the kidneys, which in turn can result in renal injury.
• Rhabdomyolysis. Alcohol is a significant cause of rhabdomyolysis, a condition marked by severe muscle tissue damage. Literature indicates that rhabdomyolysis patients may have a history of short-term alcohol intoxication and alcohol-induced coma or immobilization. The outcomes of rhabdomyolysis include life-threatening electrolyte abnormalities and acute renal failure.

Impact of Cocaine on the Kidneys

Cocaine is an addictive psychostimulant drug that in its various forms can be snorted, smoked, or dissolved into solution to be injected.^14,15 As with many other substances, the way in which cocaine is harmful to kidney health is complex. Examples of cocaine-related renal conditions, as well as some of the mechanisms that lead to these conditions, include:^6,16,17

• Vasoconstriction, renal hypertension, and malignant hypertension. Cocaine causes blood vessels to constrict, and when this constriction is sustained, it can lead to renal hypertension, which is elevated blood pressure within the delicate vasculature of the kidneys. Over time, this hypertension can damage the renal system and lead to kidney failure. Additionally, cocaine is associated with extreme systemic high blood pressure, aka malignant hypertension, which can also hasten the progression of renal injury.
• Thrombotic microangiopathy. Characterized by abnormal clot formation in small blood vessels, thrombotic microangiopathy can lead to acute kidney injury.
• Renal infarction. Cocaine can cause platelets to stick together and can create tiny clumps of platelets (i.e., microaggregates). If these conditions exist together, blood clots can develop in the kidneys, resulting in lack of blood supply and kidney damage in the form of infarcts (i.e., dead areas of tissue).
• Rhabdomyolysis. Cocaine intoxication is also associated with rhabdomyolysis, which can lead to acute renal failure.
• Oxidative stress. When metabolized, cocaine creates reactive oxygen species (ROS) that can directly damage kidney tissues.

Clearly, cocaine can have multiple detrimental effects on the renal system. However, like many other illicit drugs, cocaine is often mixed with adulterants, which are substances added to the drug to increase the quantity or alter its effects. Some of these adulterants, then, can also cause kidney injury. Studies estimate that 69% of cocaine contains levamisole, which is used as a cutting and bulking agent. Levamisole may cause cocaine-induced vasculitis, an inflammation of blood vessels that can damage kidney tissue.⁶

Impact of Opioids on the Kidneys

Opioids comprise a host of illegal and prescription drugs, including heroin, fentanyl, oxycodone (OxyContin), morphine, codeine, and others.¹⁸ While opioids are effective for pain management, they also have a high potential for abuse.¹⁹ Opioid-related kidney issues include:^5,20-23

• Rhabdomyolysis. While the exact causative mechanism isn’t always clear, high dose opioid use can lead to rhabdomyolysis, which can increase the risk of acute renal failure and death. In particular, rhabdomyolysis is a well-known complication of heroin use.
• Fluid imbalance, urinary retention. Opioids produce changes in the excretion of sodium and water, and adverse effects include urinary retention, which can lead to acute kidney injury.
• HIV, Hepatitis B and C. Injection drug use can also foster the spread of human immunodeficiency virus (HIV) along with hepatitis B and C, all of which can lead to acute or chronic kidney injury over time.
• Oxidative stress. By decreasing antioxidant function or increasing the production of free radicals, opioids can contribute to oxidative stress, which in turn can damage various cells including those in the renal system.
• Heroin-associated nephropathy. Focal segmental glomerulosclerosis (FSGS) is a type of progressive kidney disease involving injury to the glomerulus, a filtering component of the kidneys. The use of heroin is so closely associated with FSGS that the term “heroin-associated nephropathy” has been assigned to the condition.

Impact of MDMA on the Kidneys

Ecstasy, the street name for 3,4-methylenedioxymethamphetamine (MDMA), is a widely used synthetic drug with mood-enhancing properties.¹⁵ Despite its prevalent use, it’s associated with several potentially nephrotoxic effects, including:^15,24

• Hyperthermia and rhabdomyolysis. MDMA causes abnormally high body temperatures (i.e., hyperthermia). While most people can recover from hyperthermia of 104 degrees and lower, temperatures of 107 and higher can be fatal. Additionally, hyperthermia can factor into the development of nontraumatic rhabdomyolysis and acute kidney failure.
• Hyponatremia. Hyponatremia, a fluid imbalance characterized by low sodium in the blood, is the most common renal complication of MDMA use. Experts believe MDMA hyponatremia may be exacerbated by excessive beverage intake in conjunction with MDMA use. Hyponatremia may also be related to the loss of electrolytes due to MDMA-related hyperactivity involving extreme physical activity and sweating. In addition to the phenomenon merely being symptomatic of drug-related kidney dysfunction and impaired renal ability to adequately excrete free water, hyponatremia can impact other physiological processes, resulting in significant mental-status changes, seizures, coma, etc.

Treatment for Drug Misuse and Addiction

While various renal conditions may be reversible if substance use is discontinued, some effects may require various interventions along with hospitalization while others may be chronic and irreversible.^4,17 However, the best way to create sustained improvement in both physical and emotional health is to treat the substance use disorder while also addressing renal health issues.

Treatment for substance misuse is highly individualized, and multiple levels of care are available, including:²⁵

• Detox.
• Inpatient rehab.
• Outpatient programs—including Intensive Outpatient Programs (IOPs), Partial Hospitalization Programs (PHPs), and telehealth care.

A leading provider of addiction treatment, American Addiction Centers offers the full spectrum of care at various facilities scattered across the country. AAC facilities are also in-network with myriad insurance providers, which typically cover part or all treatment costs.

Reach out to connect with an AAC admissions navigator to learn more about treatment and payment options, or fill out our insurance verification form to check any insurance benefits. Caring professionals are available 24/7 to confidentially answer your questions, and help you take the first steps toward recovery today.