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Acetaminophen-Induced Renal Failure - An Overview

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Acetaminophen, also called Paracetamol, is an over-the-counter drug with an increased risk of inducing renal impairment and failure. Read on to know more.

Medically reviewed by

Dr. Yash Kathuria

Published At February 17, 2023
Reviewed AtJune 8, 2023


Acetaminophen is used to relieve mild-to-moderate pain caused by headaches, muscle aches, menstrual bleeding, colds, sore throats, toothaches, back pain, post-vaccination fever, and pain. Acetaminophen belongs to the class of medications called analgesics and antipyretics and is sold over-the-counter. It works by stopping the prostaglandin enzyme production in the brain, this further blocks the transmission of pain in the nerves. In renal failure, the kidneys lose their filtering ability, high amounts of waste accumulates, and the blood’s chemical makeup goes out of balance. As a result, acute kidney failure develops rapidly, otherwise known as acute renal failure or acute kidney injury.

What Is Acetaminophen-Induced Renal Failure?

Acetaminophen is one of the most commonly used and available analgesics and antipyretics worldwide and is easily available as it has fewer side effects than other analgesics or antipyretics. However, an overdose of Acetaminophen can cause severe and fatal liver and renal toxicity and damage when taken in high quantities or regularly over a long time. The maximum daily dose of Acetaminophen is 4.0 g, and overdoses of 7.5 g to 10.0 g can cause hepatotoxicity and nephrotoxicity.

At the normal therapeutic dosages, Acetaminophen can be toxic for the kidneys in patients with glutathione depletion in the body (chronic alcohol ingestion, starvation, or fasting) or who take drugs that stimulate the P-450 microsomal oxidase enzymes (anticonvulsants).

Causes of Acetaminophen-Induced Renal Failure

Acute tubular necrosis is a potential mechanism of renal failure associated with Acetaminophen use. Overdose or prolonged use of Acetaminophen triggers lipid peroxidation (chain of reactions of oxidative degradation of lipids), and that causes cell apoptosis, otherwise known as programmed cell death. Cell death leads to tissue necrosis (irreversible tissue death) and organ dysfunction.

What Are the Risk Factors of Acetaminophen-Induced Renal Failure?

Patient-related risk factors for drug-induced nephrotoxicity include:

  • Age: People over 60 may be prone to Acetaminophen-induced nephrotoxicity.

  • Underlying Renal Dysfunction: People with renal impairment and reduced glomerular filtration rate (less than 60 milliliters per minute per 1.73 square meter).

  • Dehydration: When there is a loss of the body’s water content, ingestion of Acetaminophen in such cases may cause possible renal failure.

  • Diabetes: People with diabetes are at an increased risk of having Acetaminophen-induced renal failure.

  • Heart Disease: People with heart conditions have an elevated risk of getting Acetaminophen-induced renal failure.

  • Infection in the Body: People having an infection in the body can be more prone to Acetaminophen-induced renal failure.

What Are the Symptoms of Acetaminophen-Induced Renal Failure?

The signs and symptoms of Acetaminophen-Induced renal failure include:

  • Decreased urine output.

  • Fluid retention causes swelling in the legs, feet, or ankles.

  • Shortness of breath.

  • Nausea.

  • Fatigue.

  • Weakness.

  • Confusion.

  • Irregular heartbeat.

  • Chest pain or pressure.

  • Coma or seizures in severe cases.

In some cases, renal failure shows no signs and symptoms and may be an incidental finding during routine tests.

What Are the Possible Complications of Acetaminophen-Induced Renal Failure?

The possible complications of Acetaminophen-induced renal failure are:

  • Fluid Accumulation: Acute renal failure can cause fluid to accumulate in the lungs, causing shortness of breath.

  • Chest Pain: Inflammation of the pericardium, a membrane that covers the heart, causing chest pain.

  • Weakness: An imbalance in the body’s water and electrolytes (blood chemistry) can lead to muscle weakness.

  • Permanent Kidney Damage: In some cases, acute renal failure can result in permanent loss of renal function or end-stage renal disease. Patients with the end-stage renal disease require either permanent dialysis (a mechanical filtration process done to remove all waste products and toxins from the body) or a kidney transplant to survive.

  • Death: Acute renal failure can cause loss of kidney function and eventual death.

When to Get Help for Acetaminophen-Induced Renal Failure?

An emergency medical opinion should be sought if the following symptoms are noticed after using Acetaminophen:

  • Nausea.

  • Vomiting.

  • Loss of appetite.

  • Weakness and lethargy.

  • Difficulty sleeping.

  • Urinating more or less.

  • Decreased mental alertness.

  • Muscle cramps.

  • Swelling of feet and ankles.

  • Dry and itchy skin.

  • High blood pressure (hypertension) that’s hard to control.

  • Shortness of breath because of accumulation of fluids in the lungs.

  • Chest pain due to fluid buildup around the heart’s lining.

How Is Acetaminophen-Induced Renal Failure Diagnosed?

Acetaminophen-induced renal failure is diagnosed in the following ways:

  • Urine Volume Measurement - Measuring urine output over 24 hours can help doctors identify the cause of renal failure.

  • Urinalysis - Analysis of a urine sample may reveal abnormalities that indicate renal failure.

  • Blood Test - Blood tests may show rapidly elevated urea and creatinine levels, which indicate renal function.

  • Imaging Test - Imaging tests like computed tomography scans (CT scans) and ultrasounds help doctors visualize the kidneys.

  • A Sample of Kidney Tissue Is Taken for Testing - In some circumstances, doctors may recommend a kidney biopsy and obtain a small sample of kidney tissue for laboratory tests. A doctor inserts a needle via the skin into the kidney to take a sample.

How Is Acetaminophen-Induced Renal Failure Treated?

The following methods of treatment for Acetaminophen-induced renal failure:

1. Treatment in case of initial renal impairment:

  • Stopping Drugs Inducing Nephrotoxicity - The drugs prescribed and causing insult to the kidney are immediately stopped.
  • Starting a Low-Protein Diet - A low-protein diet to minimize waste products in the blood is started. When the body processes protein from food, it creates waste products that the kidneys filter from the blood. Physicians advise having a low intake of protein. A dietician can be consulted for the same.
  • Drugs for Relieving Swelling - People with chronic kidney disease often retain fluid. The fluid retention leads to swollen legs and high blood pressure. Medications called diuretics, also known as water pills, help maintain the water balance in the body.

2. For treatment of end-stage renal failure:

  • Dialysis: Dialysis artificially removes all the waste products and excess water from the blood when the kidneys fail. In hemodialysis, a machine filters excess water and waste from the blood.
  • Kidney Transplant: After a transplant, medicines must be taken for the rest of the life to keep the body from rejecting the new organ. Dialysis is not required after a kidney transplant.

How to Prevent Acetaminophen-Induced Renal Failure?

  • When taking over-the-counter (OTC) pain relievers, attention should be paid to the label. Directions should be followed for OTC pain relievers such as Aspirin, Acetaminophen, Ibuprofen, and Naproxen sodium. Excessive use of these drugs may increase the risk of kidney damage. It is especially true if a person already has diabetes, kidney disease, or high blood pressure.

  • Doctors’ should be consulted to manage renal and other chronic diseases. Individuals with diabetes or high blood pressure should strictly adhere to the doctor’s recommendations and manage the conditions by following the doctor’s advice.

  • A healthy and active lifestyle should be a priority. A sensible and balanced diet should be followed.

  • Intake of alcohol should be in moderation.


Acetaminophen is associated with a significantly increased risk of developing renal dysfunction in adults. Since it is an over-the-counter drug, its unchecked usage may lead to its abuse and ill effects among people unaware of its ill effects. All kinds of medications should be taken under the guidance of a registered practitioner.

Frequently Asked Questions


Can Taking Acetaminophen Cause Kidney Failure?

Acetaminophen is linked with a significant risk of developing renal problems in adults. Excessive consumption of Acetaminophen can result in acute kidney injury, and habitual intake of Acetaminophen can result in chronic kidney disease and end-stage renal disease from papillary necrosis (death of all or part of the renal papillae) or interstitial fibrosis (accumulation of collagen and associated molecules in the interstitium).


What Is Meant by Acetaminophen-Induced Nephrotoxicity?

The recommended daily allowance of Acetaminophen is 4.0 g, and an excessive dosage between 7.5 to 10 g can result in hepatotoxicity (liver damage) since 10 % of Acetaminophen is metabolized to a toxic form called N-acetyl-p-benzoquinone imine (NAPQI) by cytochrome P450. NAPQI and Acetaminophen in excess are excreted by the kidneys resulting in acute kidney injury. The oxidative stress accompanying this condition can cause direct nephrotoxicity (kidney damage).


Is Acetaminophen Toxic to the Liver or Kidneys?

Acetaminophen is a common analgesic prescribed worldwide because of its minimal side effects. However, an overdose of Acetaminophen can result in severe and lethal damage to the liver. Long-term overdose of Acetaminophen can cause kidney damage and maximize the risk of kidney failure, particularly in patients with other health conditions or associated use of nephrotoxic drugs.


Is Acetaminophen Indicated in Chronic Kidney Disease (CKD)?

Acetaminophen is prescribed occasionally for patients with kidney disease. Those with kidney disease should consult their physician before consuming Acetaminophen. Any drug, if taken in excess, can cause certain side effects. Regularly surpassing the recommended daily intake of 4.0 g for Acetaminophen can result in the progression of chronic kidney disease and end-stage renal disease due to factors like papillary necrosis or interstitial fibrosis. Individuals with kidney disease should avoid drinking alcohol when taking analgesics.


Does Acetaminophen Consumption Cause Acute Kidney Injury?

Acetaminophen is a common analgesic prescribed worldwide because of its minimal side effects. It is considered a safe drug concerning kidney function compared to nonsteroidal anti-inflammatory drugs (NSAIDs), as these can cause acute kidney injury. However, excessive consumption of Acetaminophen can result in acute kidney injury.


Which Drugs Can Elevate the Toxicity of Acetaminophen?

The following drugs can elevate the toxicity of Acetaminophen:
- Rifampin.
- INH (Isoniazid).
- Phenytoin.
- Phenobarbital.
- Carbamazepine.
- Zidovudine.
- Trimethoprim-sulfamethoxazole.


What Are the Four Major Stages of Acetaminophen Toxicity?

Irrespective of whether acetaminophen toxicity occurs due to a single overdose or chronic habitual intake, the following are the four stages of acetaminophen toxicity:
- Phase 1: Pre-clinical toxic effects. The patient can be asymptomatic or suffer from nausea, vomiting, and abdominal pain.
- Phase 2: Hepatic (liver) injury. There can be pain in the right upper quadrant.
- Phase 3: Hepatic failure. Jaundice, hypoglycemia, lactic acidosis, shock, and so on can occur.
- Phase 4: Recovery. Patients who overcome phase 3 progress to this stage.


What Are the Side Effects of Acetaminophen?

Side effects include rashes, hives, red, peeling, or blistering skin, itching, hoarseness, swelling of the face, lips, throat, tongue, hands, feet, lower legs or ankles, eyes, and difficulty swallowing or breathing. Long-term use of Acetaminophen can cause liver and kidney damage.


Which Is the Effective Antidote for Acute Acetaminophen Toxicity?

Acetylcysteine is the preferred antidote for acetaminophen toxicity as it can reduce or prevent liver injury. This antidote is believed to supply cysteine to synthesize glutathione and form an adduct straight with the toxic metabolite of Acetaminophen called N-acetyl-p-benzoquinone imine (NAPQI). Acetylcysteine is effective within the first 8 to 10 hours.


What Are the Early Signs of Acetaminophen Toxicity?

The early indications can take up to 12 hours, including nausea, vomiting, abdominal pain, loss of appetite, irritability, generalized weakness, diarrhea, jaundice, convulsions, and coma.


How Is Acetaminophen Eliminated From the Body?

Treatment should be initiated as early as possible. Acetaminophen is eliminated in the following ways:
- Activated charcoal can absorb the Acetaminophen left in the stomach and induce vomiting.
- Gastric lavage cleans the stomach and is known as stomach pumping.
- An antidote like Acetylcysteine is given to reverse the damage caused by Acetaminophen, and medicines that retard the effects of Acetaminophen may be offered.


What Are the Signs of Liver Damage Caused by Acetaminophen?

The signs of liver damage are as follows:
- Pale skin color.
- Yellowing of skin and eyes.
- Abdominal pain.
- Fatigue and loss of appetite.
- Nausea and vomiting.
- Unusual bruising and bleeding.
- Dark urine and stools.
- Excessive sweating.
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Dr. Yash Kathuria
Dr. Yash Kathuria

Family Physician


acetaminophenacetaminophen induced renal failure
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