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toxic to the kidney

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/11/30 10:27:31」(JST)

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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 already suffering 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, cyclosporin, lithium salts, cyclophosphamide, amphotericin B
Tubular obstruction: sulphonamides, methotrexate, aciclovir, diethylene glycol, triamterene.

Acute interstitial nephritis

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

Chronic interstitial nephritis

Lithium (Li)
cyclosporine ^[3]

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^[3]
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 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 patient's creatinine clearance levels are all checked prior to a procedure. Should a reduced creatinine clearance level be found, a special contrast medium or radiocontrast that is less harmful for the patient is used.

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

References

^ Galley HF (2000). "Can acute renal failure be prevented". J R Coll Surg Edinb 45 (1): 44–50. PMID 10815380.
^ ^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.
^ ^a ^b USMLE WORLD QBanks 2009, Step1, Pharmacology, Q74

UpToDate Contents

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1. 化学療法関連腎毒性および腎不全患者における用量調整 chemotherapy related nephrotoxicity and dose modification in patients with renal insufficiency
2. アミノグリコシドによる腎毒性の症状および危険因子 manifestations of and risk factors for aminoglycoside nephrotoxicity
3. アミノグリコシドの腎毒性および聴覚毒性の病因および予防 pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity
4. シクロスポリンおよびタクロリムスの腎毒性 cyclosporine and tacrolimus nephrotoxicity
5. 成人におけるバンコマイシン投与および血清濃度のモニタリング vancomycin dosing and serum concentration monitoring in adults

English Journal

Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

Vicente-Vicente L1, Sánchez-Juanes F2, García-Sánchez O3, Blanco-Gozalo V4, Pescador M3, Sevilla MA3, González-Buitrago JM5, López-Hernández FJ6, López-Novoa JM1, Morales AI7.
Toxicology letters.Toxicol Lett.2015 Apr 16;234(2):99-109. doi: 10.1016/j.toxlet.2014.11.033. Epub 2015 Feb 9.
Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potentia
PMID 25677510

Bovine serum albumin nanoparticles for delivery of tacrolimus to reduce its kidney uptake and functional nephrotoxicity.

Zhao L1, Zhou Y1, Gao Y1, Ma S1, Zhang C1, Li J1, Wang D1, Li X1, Li C1, Liu Y2, Li X3.
International journal of pharmaceutics.Int J Pharm.2015 Apr 10;483(1-2):180-7. doi: 10.1016/j.ijpharm.2015.02.018. Epub 2015 Feb 11.
The purpose of the present study was to develop a new nanoparticulate formulation for delivery of tacrolimus to reduce its kidney distribution and functional nephrotoxicity. Tacrolimus (TAC)-loaded bovine serum albumin (BSA) nanoparticles (TAC-BSA-NPs) were prepared by emulsification-dispersion tech
PMID 25681723

Major pathways of polymyxin-induced apoptosis in rat kidney proximal tubular cells.

Azad MA1, Akter J1, Rogers KL2, Nation RL1, Velkov T3, Li J3.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2015 Apr;59(4):2136-43. doi: 10.1128/AAC.04869-14. Epub 2015 Jan 26.
Identifying the pathways involved in the apoptotic cell death that is associated with polymyxin-induced nephrotoxicity is crucial for the development of strategies to ameliorate this dose-limiting side effect and for the development of novel safer polymyxins. The primary aim of this study was to ide
PMID 25624331

Japanese Journal

Protective Effect of Hydrogen-rich Water against Gentamicin-induced Nephrotoxicity in Rats using Blood Oxygenation Level-dependent MR Imaging

MATSUSHITA Taro,KUSAKABE Yoshinori,KITAMURA Akihiro,OKADA Sakie,MURASE Kenya
Magnetic resonance in medical sciences : MRMS 10(3), 169-176, 2011-09-01
… Purpose: We assessed intrarenal oxygenation in gentamicin-induced nephrotoxicity (GIN) and the protective effect of hydrogen-rich water (HW) against GIN using blood oxygenation level-dependent magnetic resonance (MR) imaging. … Conclusions: Our findings suggested reduced oxygen utility, mainly in the cortex, in gentamicin-induced nephrotoxicity and an ameliorative effect of hydrogen-rich water against GIN. …
NAID 10029698483