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, bacterium, or plant, as well as the effect on a subs ...
in the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s. It is a
poisonous effect of some
substances, both toxic chemicals and
medications, on
kidney function
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 ...
.
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, 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 i ...
,
β-blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
,
vasodilator agents
* Local:
ACE inhibitors,
ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
,
tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
.
Direct tubular effect
*
Proximal convoluted tubule
The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...
:
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),
amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
,
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...
,
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 i ...
media,
immunoglobulins,
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 lo ...
*
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 surface (lumen ...
:
NSAIDs (e.g.
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
,
ibuprofen,
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 is taken by mouth or rectally in a suppository, used by injection, or ...
), ACE inhibitors, ciclosporin,
lithium salt
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the 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 e ...
s,
cyclophosphamide,
amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
* 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,
aciclovir
Aciclovir (ACV), 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 prevention of cytomegalovirus infections following tra ...
,
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 of ethylene glycol. It is miscible in water, alcohol, ...
,
triamterene
Triamterene (trade name Dyrenium among others) 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 known as hydro ...
.
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
β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical
structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...
,
vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...
,
rifampicin,
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 inf ...
,
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, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome ...
,
cimetidine,
furosemide
Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by m ...
,
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 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 seizures. The in ...
.
Chronic interstitial nephritis
*
Lithium salts
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the 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 el ...
*
Ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
[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 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 pre ...
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 el, λίθος, lithos, lit=stone) is a chemical element with the 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 e ...
s
*
Amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
—reversible at low doses, irreversible at high doses
*
Fluoride
*
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 analog DNA polymerase inhi ...
Other nephrotoxins
*
Lead
Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cu ...
,
mercury and
cadmium
Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like zinc, it demonstrates oxidation state +2 in most of ...
salts
*
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
Fumaric 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 salts and esters are known as fu ...
, aka food additive E297
*
Orellanine
Orellanine or orellanin is a mycotoxin found in a group of mushrooms known as the Orellani of the family Cortinariaceae. Structurally, it is a bipyridine N-oxide compound somewhat related to the herbicide diquat.
History
Orellanine first came ...
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 importa ...
is another measure of
kidney function
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 ...
, 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
Contrast-induced nephropathy (CIN) is a purported form of kidney damage in which there has been recent exposure to medical imaging contrast material without another clear cause for the acute kidney injury.
Despite extensive speculation, the actu ...
*
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, bacterium, or plant, as well as the effect on a subs ...
*
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 – specificall ...
*
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 temporary, ...
*
Onconephrology
References
Further reading
*
* {{cite journal , pmid=15957551 , year=2005 , last1=Szeto , first1=CC , last2=Chow , first2=KM , title=Nephrotoxicity related to new therapeutic compounds , volume=27 , issue=3 , pages=329–33 , journal=Renal Failure , doi=10.1081/jdi-56595, s2cid=6111262
Toxins by organ system affected
Nephrology