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 the fact that some medications are predominantly excreted by the kidneys and need their dose adjusted for the decreased kidney function (e.g., heparin, lithium).

The nephrotoxic effect of most drugs is more profound in patients already suffering from kidney failure.

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, 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
• Orellanine

Diagnosis

Nephrotoxicity is usually monitored through a simple blood test. A decreased creatinine clearance indicates poor kidney function. Normal creatinine level is between 80 - 120 μmol/L. In interventional radiology, a patient's creatinine clearance levels are all checked prior to a procedure.

Serum creatinine is another measure of kidney function, which may be more useful clinically when dealing with patients with early kidney disease.

Etymology

The word nephrotoxicity (/ˌnɛfroʊtɒkˈsɪsɪti/) uses combining forms of nephro- + tox- + -icity, yielding "kidney poisoning".

See also

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

References

1. Abyar, Selda; Khandar, Ali Akbar; Salehi, Roya; Abolfazl Hosseini-Yazdi, Seyed; Alizadeh, Effat; Mahkam, Mehrdad; Jamalpoor, Amer; White, Jonathan M.; Shojaei, Motahhareh; Aizpurua-Olaizola, O.; Masereeuw, Rosalinde (December 2019). "In vitro nephrotoxicity and anticancer potency of newly synthesized cadmium complexes". Scientific Reports. 9 (1): 14686. doi:10.1038/s41598-019-51109-9. ISSN 2045-2322. PMC 6789105. PMID 31604983.
2. Galley HF (2000). "Can acute renal failure be prevented". J R Coll Surg Edinb. 45 (1): 44–50. PMID 10815380. Archived from the original on 2005-10-18.
3. Naesens M, Kuypers DR, Sarwal M (2009). "Calcineurin inhibitor nephrotoxicity". Clin. J. Am. Soc. Nephrol. 4 (2): 481–509. doi:10.2215/CJN.04800908. PMID 19218475.
4. USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74

Further reading

• Choudhury, Devasmita; Ahmed, Ziauddin (2006). "Drug-associated renal dysfunction and injury". Nature Clinical Practice Nephrology. 2 (2): 80–91. doi:10.1038/ncpneph0076. PMID 16932399.
• Szeto, CC; Chow, KM (2005). "Nephrotoxicity related to new therapeutic compounds". Renal Failure. 27 (3): 329–33. doi:10.1081/jdi-56595. PMID 15957551.