Nephrotoxicity
Encyclopedia
Nephrotoxicity is a poison
ous effect of some substances, both toxic chemicals and medication
, on the kidney
s. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the decreased renal function
(e.g. heparin
).
Nephrotoxins are chemicals displaying nephrotoxicity.
The nephrotoxic effect of most drugs is more profound in patients who already suffer from renal impairment. Some drugs may affect renal function in more than one way.
or radiocontrast
is used which is less harmful for the patient.
Serum creatinine is another measure of renal function
, which may be more useful clinically when dealing with patients with early kidney disease.
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
ous effect of some substances, both toxic chemicals and medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, on the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the decreased renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
(e.g. heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
).
Nephrotoxins are chemicals displaying nephrotoxicity.
The nephrotoxic effect of most drugs is more profound in patients who already suffer from renal impairment. Some drugs may affect renal function in more than one way.
Cardiovascular
- General: diuretics, β-blockersBeta blockerBeta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
, vasodilator agents - Local: ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s, cyclosporine, tacrolimusTacrolimusTacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
.
Direct tubular effect
- Proximal convoluted tubule: AminoglycosideAminoglycosideAn aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...
antibiotics (e.g. gentamicinGentamicinGentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
), amphotericin BAmphotericin BAmphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
, cisplatinCisplatinCisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
, radiocontrastRadiocontrastRadiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
media, immunoglobulins, mannitolMannitolMannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator... - Distal tubule: NSAIDs (e.g. aspirinAspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, ibuprofenIbuprofenIbuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, diclofenacDiclofenacDiclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
), ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s, ciclosporinCiclosporinCiclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, lithium salts, cyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, amphotericin BAmphotericin BAmphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections... - Tubular obstruction: sulphonamidesSulfonamide (medicine)Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
, methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, aciclovirAciclovirAciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
, polyethylene glycolPolyethylene glycolPolyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
, triamterene.
Acute interstitial nephritis
- β-lactam antibioticsBeta-lactam antibioticβ-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...
, vancomycinVancomycinVancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
, rifampicinRifampicinRifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, sulphonamidesSulfonamide (medicine)Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
, ciprofloxacinCiprofloxacinCiprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
, NSAIDs, ranitidineRanitidineRanitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...
, cimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
, furosemideFurosemideFurosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
, thiazideThiazideThiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
s, phenytoinPhenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
.
Acute glomerulonephritis
Drug-induced glomerular disease is not common but there are a few drugs that have been implicated. Glomerular lesions primarily occur through immune mediated pathways rather than through direct drug toxicity.- Heroin and Pamidronate are known to cause focal segmental glomerulosclerosis
- Gold saltsGold saltsGold salts describe ionic chemical compounds of gold. The term, which is a misnomer, has evolved into a synonym for the gold compounds used in medicine...
therapy can cause membranous nephropathy - PenicillaminePenicillaminePenicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...
Causes of diabetes insipidus
- Lithium salts
- Amphotericin BAmphotericin BAmphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
-- reversible at low doses, irreversible at high doses - FluorideFluorideFluoride is the anion F−, the reduced form of fluorine when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are...
- DemeclocyclineDemeclocyclineDemeclocycline is a tetracycline antibiotic.It is derived from a strain of Streptomyces aureofaciens.-In infections:...
- FoscarnetFoscarnetFoscarnet is the conjugate base of the chemical compound with the formula HO2CPO3H2.-Uses:This phosphonic acid derivative is an antiviral medication used to treat herpes viruses, including drug resistant cytomegalovirus and herpes simplex viruses types 1 and 2...
.
Other nephrotoxins
- Heavy metalsHeavy metalsA heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...
interfere with enzymes of energy metabolism. - Aristolochic acidAristolochic acidAristolochic acids are a family of carcinogenic, mutagenic, and nephrotoxic compounds commonly found in the Aristolochiaceae family of plants, including Aristolochia and Asarum, which are commonly used in Chinese herbal medicine. Aristolochic acid I is the most abundant of the aristolochic acids...
, found in some plants and, more dangerously, in some herbal supplements derived from those plants, has been shown to have nephrotoxic effects on humans.
Surveillance
Nephrotoxicity is usually monitored through a simple blood test. A decreased creatinine clearance indicates poor renal function. Normal creatinine clearance levels are between 80 - 120 μmol/L. In interventional radiology, a patients' creatinine clearance levels are all checked prior to a procedure. Should an elevated creatinine clearance level be found, a special contrast mediumContrast medium
A medical contrast medium is a substance used to enhance the contrast of structures or fluids within the body in medical imaging...
or radiocontrast
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
is used which is less harmful for the patient.
Serum creatinine is another measure of renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
, which may be more useful clinically when dealing with patients with early kidney disease.
Further reading
- Drug-associated renal dysfunction and injury, http://www.nature.com/nrneph/journal/v2/n2/pdf/ncpneph0076.pdf
- Nephrotoxicity related to new therapeutic compounds; http://www.ncbi.nlm.nih.gov/pubmed/15957551