TOXIC RESPONSES TO THE KIDNEY

Functions of the Kidney

Total body homeostasis Excretion of metabolic wastes Synthesis and release of hormones renin and erythropoietin Regulation of extracellular fluid volume, electrolyte composition and acid-base balance

The responses of the nephron to a nephrotoxic insult

Nephrotoxic insult

Uninjured Cells

Injured Cells

Cell death

Compensatory Hypertrophy

Cellular adaptation

Cellular Prolifertation

Cellular Repair

Re-epithilization
Cellular adaptation

Differentiation

Structural and Functional Recovery of the Neuron

Mechanisms of chemically induced acute renal failure

1. Prerenal Diuretics Angiotensin receptor antagonists Angiotensin converting enzyme inhibitors Antihypertensive agents

2. Vasoconstriction Nonsteroidal anti-inflammatory drugs Radiocontrast agents Cyclosporine Amphotericin B 3. Crystalluria Sulfonamides Methothrexate Acyclovir Triamterene Ethylene glycol Protease inhibitors

4. Tubular Toxicity Aminoglycosides Cisplatin Vancomycin Pentamidine Radiocontrast agents Heavy metals Haloalkane and haloalkene cyssteine conjugates

5. Endothelial Injury Cyclosporine Mitomycin Cocaine Conjugated estrogens Quinine 6. Glumerulopathy Gold Penicillamine NSAIDS

7. Interstitial nephritis Antibiotics NSAIDs Diuretics

Specific Nephrotoxicants
1. Heavy metals
a. Mercury-HgCl2 ,affects proximal tubules b. Cadmium-causes proximal tubule dysfunction and injury

2. Halogenated Hydrocarbons
a. Chloroform-glomrulus or the distal tubule b. Tetrafluoroethylene-proximal tubule c. Bromobenzene-

3. Mycotoxins-increased urine volume, decreased osmolality, and increased excretion of low and high molecular weight proteins 4. Therapeutic Agents
a. Acetaminophen-proximal tubular necrosis with increase in BUN and plasma creatinine, decreases GFR b. Non-steroidal Anti-inflammatory Drugs

5. Aminoglycosides
a. Amphotericin B b. Cyclosporine c. Cisplatin

6. Radio-contrast Agents