Nephrotoxicity Explained

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
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
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. 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. Normal creatinine level is between 80 - 120 μmol/L.

Etymology

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

Notes and References

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. en. 9. 1. 14686. 10.1038/s41598-019-51109-9. 2045-2322. 6789105. 31604983. 2019NatSR...914686A .
Galley HF . Can acute renal failure be prevented . J R Coll Surg Edinb . 45 . 1 . 44–50 . 2000 . 10815380 . dead . https://web.archive.org/web/20051018104433/http://www.rcsed.ac.uk/journal/vol45_1/4510008.htm . 2005-10-18 .
Naesens M, Kuypers DR, Sarwal M . Calcineurin inhibitor nephrotoxicity . Clin. J. Am. Soc. Nephrol. . 4 . 2 . 481–509 . 2009 . 19218475 . 10.2215/CJN.04800908. free .
USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74