Important NEPHROTOXIRIS



Aminoglycoside Antibiotics. Although there are differences in nephrotoxic potential between specific types of aminoglycoside antibiotics, all agents of this type can cause renal injury. The ami­noglycosides are not metabolized. These drugs can be transported across both the luminal and antiluminal borders of the cells of the proximal tubule. They accumulate in these cells and induce a change in lipid metabolism. The histological hallmark of this alteration in lipid metabolism is the presence of lipid cytosegresomes in the cells of the proximal tubules. Nephrotoxicity of the aminoglycosides is related to the cumulative dose of the drug administered. The potential for de­veloping nephrotoxicity from exposure to an ami­noglycoside antibiotic is increased in patients who have underlying renal disease, vascular in­stability, depletion of the extracellular fluid vol­ume, exposure to other potentially nephrotoxic drugs, and hypokalemia. The use of drug-dosing nomograms can be of value, but frequent moni­toring of renal function and measurement of the blood concentrations of the drugs is required. If decreases in renal function develop during ad­ministration of these drugs, the drug should be discontinued if possible. If the drug is required for the management of the patient, the dose of the agent must be altered. Although the renal dys­function induced by aminoglycoside antibiotics is usually mild and reversible, when combined with other nephrotoxic insults, it can lead to acute tu­bular necrosis requiring dialytic support.

Cancer Chemotherapeutic Agents. A number of drugs used in the treatment of patients with cancer can be associated with the development of renal injury and/or specific defects in the function of the kidney. Cis-diamminedichloroplatinum (cis-platinum) is a potent renal nephrotoxin. The pattern of injury from this agent appears to resem­ble that seen with other heavy metals such asjead, arsenic, and mercury. Depending upon the mag­nitude of the injury, the acute renal failure syndrome due to the administration of cis-platinum may not be reversible. Vigorous prehydration and administration of mannitol may reduce the risk of developing renal injury.

Nonsteroidal Anti-inflammatory Drugs (NSAID). Renal toxicity due to NSAID has emerged as a very common form of drug-related nephrotoxicity. In some clinical settings it is the most common drug-related cause of renal dys­function. NSAID are potent inhibitors of prostag­landin synthesis and the toxicity of these drugs derives from this pharmacologic property. Several distinct patterns of nephrotoxicity have been re­ported (Table 35-6). Administration of NSAID has been associated with fluid retention and a pic­ture of prerenal azotemia. Particularly in patients whose maintenance of renal blood flow is depen­dent on the action of vasodilating prostaglandins, administration of NSAID may precipitate the de­velopment of the acute renal failure syndrome. Because of the relationship between prostaglan­dins and the renin-angiotensin-aldosterone axis, NSAID may cause a hyperchloremic hyperka-lemic metabolic acidosis. In addition, NSAID have been associated with the development of acute renal insufficiency due to acute interstitial nephritis. A peculiarity of this entity is the co-development of the nephrotic syndrome. The his­tological lesion is that of minimal change glom­erulopathy.