PRINCIPLES OF TOXICOLOGY - Biology East Borneo

142 NEPHROTOXICITY: TOXIC RESPONSES OF THE KIDNEYTABLE 6.4 Therapeutic Agents Known to Cause NephrotoxicityAcetaminophen (analgesic)Aminoglycoside antibioticsAmphotericin B (antibiotic)Cephalosporadine (antibiotic)Colistimethate (antibiotic)GentamycinKanamycinNeomycinPolymyxin B (antibiotic)StreptomycinTetracyclines (particularly outdated formulations) (antibiotics)gas causes massive hemolysis of red blood cells, which results in hemoglobinuria and associated renalfailure (see Chapter 4 for a general listing of hemolytic agents, methemoglobin formers, etc.).Heroin overdosage can result in a prolonged pressure on dependent muscles and a lysis of themuscle cell, leading to a release of myoglobin into the blood. Heroin may also cause some direct lysisof the muscle cells. The result can be myoglobinuria and ultimately acute renal failure. Aniline dyesare another group of chemicals that have been shown to release methemoglobin, with an associatedrenal failure.Therapeutic AgentsTable 6.4 lists a number of therapeutic agents known to cause nephrotoxicity. Acetaminophen isoxidized by the microsomal P450 oxygenase system in the renal cortex to a toxic metabolite. Themicrosomal P450 oxygenase system of the kidney is similar to that of the liver (see Chapter 5).Cephalosporadine reaches high toxic concentrations in the nephron because the organic iontransport system of the proximal tubule secretes it into the tubule. The nephrotoxicity of cephalosporadinecan be diminished by compounds that compete with the organic anion secretion system in theproximal tubule, such as probenicid. The resulting decrease in tubular concentration of cephalosporidinein tubular fluid results in elimination of toxicity.Other therapeutic agents can, in certain individuals, elicit a nephrotoxicity by an allergic type ofreaction. However, such nephrotoxicities are usually only rarely encountered.6.4 SUMMARYThe kidney performs a number of functions essential for the maintenance of life:• Elimination of waste products (particularly nitrogen-containing wastes from the metabolismof proteins) from the blood• Regulation of acid-base balance, extracellular volume, and electrolyte balanceToxic agents that disrupt these key functions can be life-threatening.The kidney is a highly metabolic organ sensitive to deprivation of oxygen, and any agent thatsignificantly impedes renal flow will cause two adverse sequelae; acute renal failure that can result indeath:• First, less blood plasma will reach the kidney, resulting in a decrease in removal of bloodwastes with a resulting increase of wastes in the blood (i.e., uremia).