Nephrotoxicity

Nephrotoxicity (pronounced “neh-freh-tok-SIS-i-tee”) is when exposure to poisonous substances (nephrotoxicants) damages your kidneys. Nephrotoxicants may be natural substances or chemicals. Certain medications can also be nephrotoxicants if you take too many of them.

Nephrotoxicity is a common cause of sudden (acute) kidney injury (AKI) and long-term (chronic) kidney disease (CKD). It can range from mild to severe. Mild cases may not be permanent — they may even be reversible. Severe cases of nephrotoxicity may be fatal.

Other names for nephrotoxicity are kidney toxicity and renal toxicity. “Renal” is another word for kidney.

What are nephrotoxicants?

There are many kinds of nephrotoxicants. Some of them are potent — only a little bit can affect your kidney function. For others, it may take large amounts to affect your kidneys. Or regular exposure to small amounts. Some examples of nephrotoxicants include:

• Heavy metals: Arsenic, lead and mercury
• Chemicals: Carbon tetrachloride (found in fire extinguishers and degreasing cleaners) and ethylene glycol (found in antifreeze)
• Mycotoxins: Ochratoxin A and citrinin, which may be found in grains, coffee and fruits
• Plant and animal toxins: Stinging insect venom (bees, wasps), snake venom and aristolochic acids (Aristolochiaceae plant family)
• Pesticides and herbicides: Organophosphates (found in insecticides) and paraquat (found in herbicides)
• Radiation: Radiation therapy

Medications and other drugs can also be nephrotoxicants.

What are nephrotoxic drugs?

Nephrotoxic medications may include:

• ACE inhibitors
• Antidepressants
• Antiretrovirals
• ARBs
• Benzodiazepines
• Chemotherapy drugs
• Diuretics
• Painkillers (analgesics), including acetaminophen and NSAIDs, like ibuprofen
• Proton pump inhibitors

The following substances can also damage your kidneys:

• Cocaine
• Heroin
• Ketamine
• Methadone
• Methamphetamine

What are the symptoms of nephrotoxicity?

You might not have any noticeable symptoms if you have mild nephrotoxicity. But severe nephrotoxicity can affect how well your kidneys work. As your kidneys lose function, symptoms may include:

• Dry and itchy skin
• Foamy pee
• High blood pressure
• Loss of appetite
• Nausea and vomiting
• Peeing less than expected
• Skin darkening
• Swelling, especially in your hands, ankles and feet

What does ‘nephrotoxicity mechanism’ mean?

Nephrotoxicity mechanisms are the different ways nephrotoxicants can damage your kidneys. These include:

• Crystal nephropathy: Nephrotoxins cause crystals to form in your kidneys. The crystals can block the tiny tubes (tubules) in your kidneys. Tubules help move water, nutrients, minerals and wastes (toxins).
• Glomerular damage: Your glomeruli are groups of tiny blood vessels. They perform the first step in filtering toxins from your blood. Damage to your glomeruli affects how well your kidneys filter your blood.
• Inflammation: Nephrotoxins can cause allergic reactions. The reactions cause inflammation and scar tissue to build up in your kidneys. This may lead to glomerulonephritis and acute and chronic tubulointerstitial nephritis.
• Renal tubular toxicity: Nephrotoxins damage the tubules in your kidneys.
• Thrombotic microangiopathy: A blood clot (thrombosis) in tiny blood vessels affects your kidneys.

Complications of nephrotoxicity

Without proper diagnosis and treatment, severe nephrotoxicity can cause chronic kidney disease. It may also cause kidney failure. Kidney failure is fatal without treatment.

How doctors diagnose nephrotoxicity

Healthcare providers will order kidney function tests. Kidney function tests involve blood and urine (pee) tests. They tell your provider how well your kidneys filter waste.

Your provider may also recommend imaging tests, like a CT urogram, a kidney ultrasound and an MRI. A kidney biopsy may also be necessary to help them determine the best treatment.

How is nephrotoxicity treated?

Nephrotoxicity treatment depends on the cause and how severe your kidney damage is. In mild cases, you may only need to avoid the nephrotoxin. But sometimes, the medications that cause nephrotoxicity help a more severe condition. For example, chemotherapy to treat cancer. In those cases, providers will try to reduce your exposure and manage your symptoms.

If nephrotoxins cause inflammation, providers may suggest steroids. In severe cases, you may need dialysis or a kidney transplant. Dialysis is a treatment that filters your blood when your kidneys don’t work. A kidney transplant replaces your damaged kidney with a healthy donor kidney.

When should I see my healthcare provider?

Mild cases of nephrotoxicity often don’t cause any symptoms. So, it’s a good idea to schedule annual checkups with a primary care provider (PCP). Your PCP usually checks your kidney function as part of a blood test. Your results can help them catch kidney damage and determine its cause before you have any symptoms. You should also schedule an appointment with a provider if you have certain signs of kidney damage. These include:

• Feeling really tired
• Not peeing as much as you think you should
• Loss of appetite
• Trouble focusing and sleeping
• Swelling, especially around your ankles and feet

During your appointment, you may want to ask the following questions:

• What’s causing nephrotoxicity?
• Do I have mild or severe kidney damage?
• Is the kidney damage permanent?
• What tests do you recommend?
• What treatment do you recommend?
• How can I help keep my kidneys healthy?
• How often should a provider check my kidneys?
• Can you recommend a kidney specialist (nephrologist)?

What can I expect if I have nephrotoxicity?

Your outlook depends on many factors, including the:

• Type of nephrotoxicant(s)
• Amount of exposure
• Length of exposure
• Amount of damage to your kidneys

Your age and overall health also play a role. In some cases, you may have mild, reversible kidney damage. Other cases may cause permanent kidney damage and may even be fatal. Getting an official diagnosis and proper treatment is very important. It helps increase your chances of a full recovery.

What happens to your body when your kidneys start shutting down?

If you have kidney failure, toxins will build up in your blood (uremia). Without dialysis or a kidney transplant, kidney failure is fatal. You may survive a few days or weeks without treatment.

Can this be prevented?

It’s challenging to prevent exposure to all nephrotoxicants. They’re common in many medications, therapies and everyday life in general. But you can help reduce your risk of exposure by:

• Drinking filtered water
• Testing well water for heavy metals and other nephrotoxicants
• Taking medications only as directed
• Using personal protective equipment (PPE) if you work around nephrotoxicants
• Washing fruits and veggies to remove pesticides
• Never mixing cleaning products or household chemicals
• Storing grains and other foods properly to prevent mold from growing
• Avoiding addictive nephrotoxic substances
• Wearing PPE or proper clothing and footwear around venomous insects or animals