Antibiotic-related nephrotoxicity.
The toxicity of aminoglycosides is related to their concentrative uptake by proximal tubular cells and their capacity to interact with critical intracellular targets. Concentrative uptake is mediated by adsorptive endocytosis across the apical membrane followed by sequestration within lysosomes. The fundamental mechanism underlying the toxicity of these organic polycations is their capacity to interact electrostatically with and disrupt the metabolism of anionic phospholipids, especially the phosphoinositides. Polyaspartic acid, a polyanionic peptide, protects against aminoglycoside nephrotoxicity by forming electrostatic complexes with these drugs and inhibiting their interaction with critical intracellular targets. The selective toxicity of beta-lactams towards renal proximal tubular cells is related to their concentrative uptake via the organic anion transport system. Lipid peroxidation appears to play a major role in the toxicity of cephaloridine. Depressed mitochondrial respiration secondary to acylation of the mitochondrial transporter for succinate has been implicated in the pathogenesis of toxicity caused by other cephalosporins and carbapenems. The predilection of the kidney for amphotericin B toxicity is unclear as little drug is excreted by the kidneys. Toxicity is manifested by increased renal vascular resistance, depression of RBF and GFR, and altered tubular function that reflects the capacity of this drug to interact with cholesterol-containing membranes and increase membrane permeability to ions including potassium, hydrogen, calcium, and magnesium.
Kaloyanides
G J
GJ
Department of Medicine State University of New York.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000617:Aminoglycosides; D000666:Amphotericin B / Q000009:adverse effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007769:Lactams; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012307:Risk Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007769:Lactams; D010743:Phospholipids; D000666:Amphotericin B