Nephrotoxicity is
toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...
in the
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s. It is a
poison
A poison is any chemical substance that is harmful or lethal to living organisms. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figurati ...
ous effect of some
substances, both toxic chemicals and
medications
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
, on
kidney function
Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging.
Renal physiology, Functions of a healthy kidney include ...
.
There are various forms,
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
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...
, lithium).
Types of toxicity
Cardiovascular
* General:
diuretics
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
,
β-blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention) ...
,
vasodilator
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...
agents
* Local:
ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...
s,
ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...
,
tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...
.
Direct tubular effect
*
Proximal convoluted tubule
The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...
:
Aminoglycoside
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
antibiotics (e.g.,
gentamicin
Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...
),
amphotericin B
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...
,
cisplatin
Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
,
radiocontrast
Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography (contrast CT), projectional radiography, and fluoroscopy. Radiocontrast agents are typically iod ...
media,
immunoglobulin
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
s,
mannitol
Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to l ...
*
Distal tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.
Physiology
It is partly responsible for the regulation of potassium, sodium, calcium, and pH.
On its Apical membrane, apica ...
:
NSAIDs (e.g.
aspirin
Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
,
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
,
diclofenac
Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It can be taken orally (swallowed by mouth), inserted rectally as a ...
), ACE inhibitors, ciclosporin,
lithium salt
Lithium (from , , ) is a chemical element; it has symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid element. Like all alkali metals, ...
s,
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
,
amphotericin B
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...
* Tubular obstruction:
sulphonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. B ...
,
methotrexate
Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
,
aciclovir
Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include the prevention of cytomegalovirus infections following tran ...
,
diethylene glycol
Diethylene glycol (DEG) is an organic compound with the formula (HOCH2CH2)2O. It is a colorless, practically odorless, and hygroscopic liquid with a sweetish taste. It is a four carbon Dimer (chemistry), dimer of ethylene glycol. It is miscible in ...
,
triamterene
Triamterene (traded under names such as Dyrenium and Dytac) is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is kno ...
.
Acute interstitial nephritis
Main article :
Acute interstitial nephritis
Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules ...
*
β-lactam antibiotics,
vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...
,
rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...
,
sulphonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. B ...
,
ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...
,
NSAID
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s,
ranitidine
Ranitidine, previously sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It was commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellis ...
,
cimetidine
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
With the development of proton pump ...
,
furosemide
Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can ...
,
thiazide
Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...
s,
phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...
.
Chronic interstitial nephritis
*
Lithium salts
Lithium (from , , ) is a chemical element; it has symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid element. Like all alkali metals, ...
*
Ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...
[USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74]
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
Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...
and
Pamidronate
Pamidronic acid or pamidronate disodium or APD (marketed as Aredia among others), is a nitrogen-containing bisphosphonate used to prevent osteoporosis.
It was patented in 1971 and approved for medical use in 1987.
Medical uses
It is used to pr ...
are known to cause focal segmental glomerulosclerosis
*
Gold salts
Gold-containing drugs are pharmaceuticals that contain gold. Sometimes these species are referred to as "gold salts". "Chrysotherapy" and "aurotherapy" are the applications of gold compounds to medicine. Research on the medicinal effects of g ...
therapy can cause membranous nephropathy
*
Penicillamine
Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, ...
Causes of diabetes insipidus
*
Lithium salt
Lithium (from , , ) is a chemical element; it has symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid element. Like all alkali metals, ...
s
*
Amphotericin B
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococ ...
—reversible at low doses, irreversible at high doses
*
Fluoride
Fluoride (). According to this source, is a possible pronunciation in British English. is an Inorganic chemistry, inorganic, Monatomic ion, monatomic Ion#Anions and cations, anion of fluorine, with the chemical formula (also written ), whose ...
*
Demeclocycline
*
Foscarnet
Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate Structural analog, analog ...
Other nephrotoxins
*
Lead
Lead () is a chemical element; it has Chemical symbol, symbol Pb (from Latin ) and atomic number 82. It is a Heavy metal (elements), heavy metal that is density, denser than most common materials. Lead is Mohs scale, soft and Ductility, malleabl ...
,
uranium
Uranium is a chemical element; it has chemical symbol, symbol U and atomic number 92. It is a silvery-grey metal in the actinide series of the periodic table. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons. Ura ...
,
mercury, and
cadmium
Cadmium is a chemical element; it has chemical symbol, symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12 element, group 12, zinc and mercury (element), mercury. Like z ...
salts
*
Aristolochic acid
Aristolochic acids () are a family of carcinogenic, mutagenic, and nephrotoxic phytochemicals commonly found in the flowering plant family Aristolochiaceae (birthworts). Aristolochic acid (AA) I is the most abundant one. The family Aristolochiace ...
, found in some plants and in some herbal supplements derived from those plants, has been shown to have nephrotoxic effects on humans.
*
Rhubarb
Rhubarb is the fleshy, edible stalks ( petioles) of species and hybrids (culinary rhubarb) of ''Rheum'' in the family Polygonaceae, which are cooked and used for food. The plant is a herbaceous perennial that grows from short, thick rhizomes. ...
contains some nephrotoxins which can cause inflammation of the
kidneys
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
in some people.
*
Fumaric acid
Fumaric acid or ''trans''-butenedioic acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297.
The sa ...
, aka food additive E297, is nephrotoxic in high doses
[European Commission: ]
*
Lilium
''Lilium'' ( ) is a genus of Herbaceous plant, herbaceous flowering plants growing from bulbs, all with large and often prominent flowers. Lilies are a group of flowering plants which are important in culture and literature in much of the world ...
is very toxic to cats, often resulting in death by
acute kidney failure
Acute may refer to: Language
* Acute accent, a diacritic used in many modern written languages
* Acute (phonetic), a perceptual classification
Science and mathematics
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf m ...
, or permanent renal dysfunction.
Diagnosis
Nephrotoxicity is usually monitored through a simple blood test. A decreased
creatinine clearance
Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.
Functions of a healthy kidney include maintaining a person's fluid ...
indicates poor kidney function. In interventional radiology, a patient's creatinine clearance levels are all checked prior to a procedure.
Serum creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an impor ...
is another measure of
kidney function
Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging.
Renal physiology, Functions of a healthy kidney include ...
, which may be more useful clinically when dealing with patients with early kidney disease. Normal creatinine level is between 80 - 120 μmol/L.
Etymology
The word ''nephrotoxicity'' () uses
combining forms of ''
nephro-'' + ''
tox-'' + ''
-icity'', yielding "kidney poisoning".
See also
*
Contrast-induced nephropathy
*
Toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...
*
Neurotoxicity
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
*
Ototoxicity
Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and tempora ...
*
Onconephrology
References
Further reading
*
*
{{Authority control
Toxins by organ system affected
Nephrology