Nephrotoxicity

Nephrotoxicity (from Greek: nephros, "kidney") is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity.^[1] 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.

Types of toxicity

Cardiovascular

• General: diuretics, β-blockers, vasodilator agents
• Local: ACE inhibitors, cyclosporine,^[2] tacrolimus.^[2]

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, polyethylene glycol, triamterene.

Acute interstitial nephritis

• β-lactam antibiotics, vancomycin, rifampicin, sulphonamides, ciprofloxacin, NSAIDs, ranitidine, cimetidine, furosemide, thiazides, phenytoin.

Chronic interstitial nephritis

• Lithium
• cyclosporine ^[3]

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 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

• Heavy metals interfere with enzymes of energy metabolism.
• Aristolochic acid, 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 medium 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.

References

1. ^ Galley HF (2000). "Can acute renal failure be prevented". J R Coll Surg Edinb 45 (1): 44–50. PMID 10815380. http://www.rcsed.ac.uk/journal/vol45_1/4510008.htm. 
2. ^ ^{a b} 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. 
3. ^ USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74
4. ^ USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74

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

See also

• Toxicity
• Neurotoxicity
• Ototoxicity