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- Introduction
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2. Overview of nonclinical safety assessment
- Dr. Claudette L. Fuller
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3. Biological safety testing: supporting medical device combination products
- Dr. Christine L. Lanning
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4. Regulatory guidance on toxicity testing of pharmaceuticals: ICH
- Dr. John Kapeghian
- Basics of Non-clinical Toxicity Testing
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6. Acute, subchronic, and chronic toxicity testing
- Mr. Gregory Ruppert
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7. Safety pharmacology in human pharmaceutical development
- Dr. R. Dusty Sarazan
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8. Genetic toxicology
- Dr. Roderick Todd Bunch
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9. Reproductive and developmental toxicology
- Dr. Alan Hoberman
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10. Juvenile toxicity testing
- Dr. Alan Hoberman
- Dr. Elise Lewis
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11. Pharmacokinetics, toxicokinetics and safety margins
- Dr. Mark Rogge
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12. Toxicity testing of impurities and metabolites
- Dr. Kurt Black
- Organ System Toxicity Testing
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13. Drug induced liver injury: a clinical perspective
- Prof. Victor Navarro
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14. Toxicology of the kidney
- Prof. Lawrence Lash
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15. Toxicology of the cardiovascular system
- Dr. Peter Siegl
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16. Toxicology of the immune system
- Dr. Leigh Ann Burns Naas
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17. Toxicology of the developing immune system
- Dr. Leigh Ann Burns Naas
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18. Hematology interpretation for toxicity studies
- Dr. Nancy Everds
- New Methods for Assessing Toxicity
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19. Introduction to toxicogenomics and example case studies
- Dr. Cindy Afshari
- Special Cases for Toxicity Testing
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21. Approaches to nonclinical vaccine development
- Dr. Lisa Plitnick
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22. Toxicity testing of oncology drugs: unraveling the last 15 years of progress
- Dr. Krishna Allamneni
- Archived Lectures *These may not cover the latest advances in the field
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23. Cellular and molecular toxicology
- Dr. Dominic Williams
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24. Overview of non-clinical safety assessment in drug development
- Dr. Danuta Herzyk
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27. Reproductive and developmental toxicology
- Dr. Alan Hoberman
- Dr. Elise Lewis
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28. Non-clinical toxicity testing for vaccines
- Dr. Lisa Plitnick
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29. Toxicity testing for oncology drugs
- Dr. Theresa Reynolds
- Dr. Krishna Allamneni
Printable Handouts
Navigable Slide Index
- Introduction
- Lecture outline
- Renal structure
- Nephron heterogeneity
- Renal functions
- Filtration and reabsorption of electrolytes, water
- Susceptibility of the kidney to toxicant injury
- Renal blood flow
- Renal concentrating mechanisms
- Filtration, absorption, excretion
- Basic renal transport mechanisms
- Organic anion and cation transport processes
- Role of kidneys in fluid balance
- Bioactivation
- In vivo assessment of renal function
- Determination of GFR
- Relationships between SCr, BUN and GFR
- Parameters determined in typical urinalysis
- Proteinuria
- Enzymuria
- In vitro models for kidney toxicology
- In vitro models - isolated perfused kidney
- In vitro models - renal slices
- In vitro models - isolated perfused tubules
- In vitro models - isolated tubules/tubular fragments
- Models: suspensions of freshly isolated renal cells
- In vitro models - primary renal cell cultures
- In vitro models - renal cell culture lines
- Selected immortalized, continuous renal cell lines
- Acute renal failure
- Chronic renal failure
- Response to a nephrotoxicant
- Mechanisms of renal cell injury
- Nephron segment-specificity of nephrotoxicants
- Cadmium
- Cisplatin
- Halocarbon cysteine conjugates
- Trichloroethylene metabolism
- DCVC mechanisms of toxicity
- GSH and S-conjugate transport
- Structures of beta-lactam antibiotics
- Accumulation of beta-lactam in renal PT cells
- Mechanisms of toxicity of cephaloridine
- Bioactivation of acetaminophen
- References
- Acknowledgments
Topics Covered
- Renal structure and functions
- Renal blood flow
- Renal concentrating and transport mechanisms
- Role of kidneys in fluid balance
- In vivo assessment of renal function
- In vitro models to study kidney toxicology
- Classification of nephrotoxic injury
- Mechanisms of renal cell injury
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Lash, L. (2015, April 30). Toxicology of the kidney [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/QUHX8060.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Lawrence Lash has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
This is Lawrence Lash. I'm a professor in the Department of Pharmacology
at Wayne State University School of Medicine in Detroit, Michigan,
and the topic of my talk will be the Toxicology of the Kidney.
0:15
As you can see on this slide, there will be five major sections to the talk.
The first section, I will review a few key points about renal structure and physiology
that are important in terms of understanding why the kidney
is susceptible to toxic injury and what is unique about renal structure and function.
In the second section we will specifically address factors that are important
in determining susceptibility of the kidney to toxicant injury.
In the third and fourth sections, I will talk about different models,
first in vivo models and then various in vitro models,
that are used to discuss and study toxicology of the kidney,
and then finally as some illustrations of how chemicals can produce toxicity
in the kidney and some of the unique features as case studies,
we will review briefly some examples: heavy metals,
cadmium and mercury principally; halogenated solvents; antibiotics;
and finally analgesics.
1:30
This slide illustrates some aspects of renal structure. First there's a nephron
that is a deep nephron that goes all the way into the inner medulla
as well as a superficial nephron on the right, which only goes to the outer stripe
inner medulla border. The slide illustrates the different major epithelial cell types
beginning with the glomerulus. This is number one.
This leads into the proximal tubules, which is number two,
first the proximal convoluted tubule in the cortex, then in the cortex
and outer stripe of the outer medulla, one has the proximal straight tubule,
then flows into the thin descending limb, then thick ascending limb, and finally
into the distal tubule, connecting tubule, and into the collecting duct.
And the importance of understanding this is that each cell type,
each epithelial cell type, has a specific structure and function
that, while allowing the kidney to have its unique physiology
also provides some unique features to the susceptibility to chemically-induced injury.