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Hi,
I need to know what are the most important parameters of nephrotoxicity to be
studied for a given antimicrobial dug (aminoglycosides, Polymyxin B etc) in
animal models (rats).
For how long that drug will be administered (chronic and acute)? and what
dosage? ect.
I need this information for toxicological studies.
Your help is appreciated.
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My lab is presently investigating exacerbation of NSAID-induced renal
toxicity by gentamicin and other such perioperative minefileds. We use a rat
preparation with several indices of renal toxicity .
1. plasma clearances of iothalamate to approximate GFR and
paraaminohippurate to approximate renal plasma flow
2. plasma and urinary electrolytes and osmolality
3. histopathology of kidney
No one index is enough.
Gentamicin alone can trigger all three indices.
Hope that this helps provide a basis for your further consideration.
Laurie Mather
Professor of Anaesthesia and Analgesia (Research)
University of Sydney at Royal North Shore Hospital
St Leonards NSW 2065 Australia
Ph +61 2 9926 8420; Fax +61 2 9906 4079
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Hi,
I would like to study the nephrotoxicity of an antibiotic but I don't know
which are the most important parameters of nephrotoxicity (creatinine,
histopathology of the kidney etc)
Your help is greatly appreciated.
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Dear Abdel Omri
This is an interesting question. It would appear, that there are a number
of proposed methods for measuring the nephrotoxicity of antibiotics.
These include NAG, renal proteins, creatinine, phospholipids and true
antibiotic clearance. I have some experience using various markers in an
animal model.
Creatinine is an insensitive and slow changing marker. Changes in
creatinine change 48 to 72 hours after the renal damage has occurred.
NAG and renal proteins are a bit more sensitive, however can also be
disturbed by other pathology.
Changes in aminoglycoside clearance would appear to be more sensitive
than all the above indices in my animal model. I need to complete the
remainder of my experiments to sort this out. However, anecdotal
evidence in humans would also appear to support this.
It would appear that the most sensitive and earliest marker of renal
damage is the measurement of phospholipiduria. I have some experience
in the measurement of this index of aminoglycoside induced
nephrotoxicity using an animal model.
Carl Kirkpatrick
Department of Clinical Pharmacology
Christchurch Hospital
New Zealand
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