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Amphotericin B Nephrotoxicity
Amphotericin B Nephrotoxicity
Amphotericin B Nephrotoxicity
Jun-Ki Park
5/17/11
1997GuidelinesfortheUseofAntimicrobialAgentsinNeutropenicPatients
withUnexplainedFever.Hughesetal.CID1997
Rate of Nephrotoxicity
64 %
49 %
53 %
Clinical Manifestations
Renal insufficiency
Risk Factors
Dose dependence:
(low risk at doses less than 0.5mg/kg per day and
cumulative dose of less than 600mg
Dehydration
FigureA.Cumulative
probabilityofdeveloping
modseverenephrotoxicity,
stratifiedbymeandaily
amphotericinBdosage.
FigureB.Cumulative
probabilityofdeveloping
modseverenephrotoxicity,
stratifiedbyNr.Of
independentriskfactors
(amikacinorcyclosporine
treatment,meandaily
amphotericinBdose35mg,
weight90kg,malesex,and
chronicrenaldisease).
Harbarthetal.AmJMed.2001
Wingardetal.CID2001
Pathogenesis
Direct toxic effects:
Amphotericin inserts into cell membranes, creating
pores that increase cell permeability, leading to
hypoerkalemia, hypomagnesemia, distal RTA.
Deoxycholate toxicity (bile salt, traditional Ampho B
solubilizing agent)
Vasoconstriction of afferent arterioles
Indirect effect:
Decreased GFR via Tubuolglomerular Feetback
mediated vasoconstriction.
Andreolietal.KI1973
Zietzeetal.Nat.Rev.Nephrol.2009
Steinmetzetal.JCI1970
Steinmetzetal.JCI1970
Steinmetzetal.JCI1970
Kimetal.JLabClinMed2001
Zageretal.KI1992
Sawayaetal.JClinInvest1991
Sawayaetal.JClinInvest1991
Prevention
Salt loading
Llanosetal.KI1991
Llanosetal.KI1991
Amphocil/Amphotec (amphotericin B
colloid dispersion (ABCD)) with a disclike structure)
Whiteetal.ClinicalInfectiousDiseases1998
AmBisome
Walshetal.NEJM1999
Nephrotoxicitydefinedby:
sCrtwoormoretimesthe
baseline
Concomitantnephrotoxicdrugs:
Aminoglycosides
Cyclosporine
Foscarnet
Thefollowingnumbersofpatients
tookvariousnumbersofdrugs:
0or1:79patientsreceiving
Ambisomeand92AmpB
2ormore:264and252,resp.
3ormore:120and119,resp.
Walshetal.NEJM1999
Walshetal.NEJM1999
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