Nephrotoxicity

Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function.^[1] There are various forms,^[2] and some drugs may affect kidney function in more than one way. Nephrotoxins are substances displaying nephrotoxicity.

Nephrotoxicity should not be confused with some medications predominantly excreted by the kidneys needing their dose adjusted for the decreased kidney function (e.g., heparin, lithium).

Types of toxicity

Cardiovascular

• General: diuretics, β-blockers, vasodilator agents
• Local: ACE inhibitors, ciclosporin,^[3] tacrolimus.^[3]

Direct tubular effect

• Proximal convoluted tubule: Aminoglycoside antibiotics (e.g., gentamicin), amphotericin B, cisplatin, radiocontrast media, immunoglobulins, mannitol
• Distal tubule: NSAIDs (e.g. aspirin, ibuprofen, diclofenac), ACE inhibitors, ciclosporin, lithium salts, cyclophosphamide, amphotericin B
• Tubular obstruction: sulphonamides, methotrexate, aciclovir, diethylene glycol, triamterene.

Acute interstitial nephritis

Main article : Acute interstitial nephritis

• β-lactam antibiotics, vancomycin, rifampicin, sulphonamides, ciprofloxacin, NSAIDs, ranitidine, cimetidine, furosemide, thiazides, phenytoin.

Chronic interstitial nephritis

• Lithium salts
• Ciclosporin^[4]

Acute glomerulonephritis

Drug-induced glomerular disease is not common but there are a few drugs that have been implicated. Glomerular lesions occur primarily through immune-mediated pathways rather than through direct drug toxicity.

• Heroin and Pamidronate are known to cause focal segmental glomerulosclerosis
• Gold salts therapy can cause membranous nephropathy^[4]
• Penicillamine

Causes of diabetes insipidus

• Lithium salts
• Amphotericin B—reversible at low doses, irreversible at high doses
• Fluoride
• Demeclocycline
• Foscarnet

Other nephrotoxins

• Lead, uranium, mercury, and cadmium salts^[1]
• Aristolochic acid, found in some plants and in some herbal supplements derived from those plants, has been shown to have nephrotoxic effects on humans.
• Rhubarb contains some nephrotoxins which can cause inflammation of the kidneys in some people.
• Fumaric acid, aka food additive E297, is nephrotoxic in high doses^[5]
• Lilium is very toxic to cats, often resulting in death by acute kidney failure, or permanent renal dysfunction.^[6]

Diagnosis

Nephrotoxicity is usually monitored through a simple blood test. A decreased creatinine clearance indicates poor kidney function. In interventional radiology, a patient's creatinine clearance levels are all checked prior to a procedure.^{[citation needed]}

Serum creatinine is another measure of kidney function, which may be more useful clinically when dealing with patients with early kidney disease. Normal creatinine level is between 80 - 120 μmol/L.^{[citation needed]}

Nephrotoxicity in the Medical Workplace

Occupational Exposure

Some of the workplaces that have a higher risk of nephrotoxicity usually include hospitals, laboratories, and sanitation jobs. A few of the main nephrotoxins that these workers might be exposed to include heavy metals, solvents, chemicals, and even compounds that are found in certain medicines.(1) There is a higher risk is due to these workers being exposed to these substances more often. Workers that are employed in these workplaces can be exposed through the inhalation, dermal contact, or ingestion of these substances. For example, laboratory worker have to deal with chemicals like formaldehyde and other solvent-based chemicals, which can build up in the kidneys.(3) Healthcare workers can be exposed to some of the substances that can be found in certain medicines.(4) Sanitation workers can be exposed through the cleaning products that they work with. The longer you are exposed to these substances, the higher chance your kidney is going to be affected by the poisonous effects of the nephrotoxins. This means that the kidneys will lose their ability to filter waste, and can lead to nephrotoxicity or kidney disease.(2)^[7]

How the Chemical Reaction Occurs

Prevention and Control

Preventing nephrotoxicity in medical and hospital settings requires a multi step approach, including preventative measures and control and response to people that have been exposed. This begins with integrating in substitutions for harmful nephrotoxic chemicals, creating exposure controls, proper administrative policies, and appropriate Personal Protective Equipment (PPE).^{[8] [9][10][11][12][13]} Another important step is control and response, early detection of symptoms, and symptom monitoring for workers and patients that may have higher exposure levels to chemicals that cause nephrotoxicity. ^[10]

Medical settings have several different ways of preventing and minimizing the risk of nephrotoxicity. Substitutions to nephrotoxic chemicals commonly used in the medical setting should include replacing disinfectants, solvents, antibiotics, chemotherapy drugs, and Non-steroidal Anti-Inflammatory Drugs (NSAIDS) with safer chemicals for healthcare workers and patients to use.^[8] Hospital settings should also provide exposure controls like closed system drug transfer devices, maintaining good ventilation in rooms where drugs are being used, and biological safety cabinets.^[10] Solid administrative controls like proper labelling, hazard communication, training programs for employees, and using Safety Data Sheets (SDS) can minimize the risk of exposure further.^[9] Employees should be required to wear proper PPE when handling nephrotoxic substances: including gloves, full coverage safety gowns, and respiratory protection over their mouth and nose. ^[8]

Control and response is also important, and can include baseline and periodic kidney function testing among exposed workers and patients,^[11] and having protocols for hazardous waste disposal/management and contamination cleanup.^[9] If there is a chemical spill or direct exposure, there should be spill kits, emergency eyewash stations, and immediate medical attention and evaluations offered.^[9] Using good waste disposal protocols can also help prevent contamination and cross-contamination of healthcare workers and patients.^[12] Patients that must be given nephrotoxic substances should have kidney testing and monitoring evaluations done before and after the drugs are administered to ensure that they receive medical treatment as needed for any resulting nephrotoxicity symptoms. ^[13]

Etymology

The word nephrotoxicity (/ˌnɛfroʊtɒkˈsɪsɪti/) uses combining forms of nephro- + tox- + -icity, yielding "kidney poisoning".^{[citation needed]}

See also

• Contrast-induced nephropathy
• Toxicity
• Neurotoxicity
• Ototoxicity
• Onconephrology