Kidney aminoglycosides

Hypomagnesemia is usually associated with disorders of the intestinal tract or kidneys. Drugs (e.g., aminoglycosides, amphotericin B, cyclosporine, diuretics, digitalis, cisplatin) or conditions that interfere with intestinal absorption or increase renal excretion of magnesium can cause hypomagnesemia. 

Renal cell lines have been utilized to a limited extent for evaluation nephrotoxins. A rabbit kidney cell line (LLC-RKi) has been utilized for evaluating nephrotoxic antibiotics (Viano et al., 1983 Hottendorf et al., 1987 Williams et al., 1988). LLC-PKi cells have by far been the most widely employed cell line for studying drug-induced nephrotoxicity, specifically in the evaluation of aminoglycoside antibiotics (Hori et al., 1984 Schwertz et al., 1986 Williams et al., 1986b Holohan et al.,... 

The morphological alterations induced by aminoglycosides in LLC-PKi cells correlated well with in vivo histological findings in the kidney, including the formation of secondary lysosomal inclusions referred to as myeloid bodies. 

Hori, R., Yamamoto, S., H., Kohno, M. and Inui, K. (1984). Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PKi) a model system for aminoglycoside nephrotoxicity. Pharmacol. Exp. Ther. 230 742-748. 

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

Gentamicin, as with other aminoglycosides, is excreted through the kidney, and in renal impairment there is the risk of accumulation. Consequently doses are reduced and dosing interval increased in patients with renal impairment. 

The future development of aminoglycosides for use in veterinary medicine will depend on two main factors. The first is the cost of producing them as the synthetic process is expensive. The second is depdendent on discovering an aminoglycoside that does not accumulate and remain in kidney tissue for prolonged periods, resulting in a shorter withdrawal period for food producing animals (11). 

A major clinical distinction between the effects on the inner ear and the kidney is the fact that the renal effects are reversible while the effects on the inner ear are irreversible, leading to permanent loss of balance or auditory function. Furthermore, renal insults can more easily be monitored and thereby largely prevented, while monitoring of impending auditory or vestibular damage is not always possible. Ototoxic side effects frequently develop after cessation of aminoglycoside treatment, sometimes delayed by weeks. This review will therefore focus on the ototoxic side effects as a major unresolved issue in aminoglycoside toxicity. 

WARNING Systemic absorption of oral route may cause neuro/oto/nephrotox may result resp paralysis possible w/ any route of administration Uses Hepatic coma, bowel prq) Action Aminoglycoside, poorly absorbed PO -1- GI bacterial flora Dose Adults. 3-12 g/24- h PO in 3-4 doses Peds. 50-1 (X) mg/kg/24 h PO in 3-4 doses Caution [C, /-] Renal failure, neuromuscular disorders, hearing impair Contra Intestinal obst Disp Tabs, PO soln SE Hearing loss w/ long-term use rash, NA EMS Use neuromuscular blockers w/ caution, reduced dose may be necessary t bleeding risk w/ concurrent anticoagulant use OD May cause neuromuscular block and kidney failure calcium salts can be used to revise neuromuscular block... 

In fact elderly people have a reduced creatinine clearance, often balanced by the decline in creatinine input with a resulting normal serum creatinine. This is clinically important because drugs which are cleared through the kidneys need to be given in scaled down amounts to prevent cumulation and possible toxicity - e.g., gentamicin and other parenteral aminoglycosides, digoxin. 

The aminoglycosides decrease the fidelity of translation by binding to the 30S subunit of the ribosome. This permits the formation of the peptide initiation complex but prohibits any subsequent addition of amino acids to the peptide. This effect is due to the inhibition of polymerization as well as to the failure of tRNA and mRNA codon recognition. Aminoglycosides are ototoxic (i.e., may produce partial deafness), damaging the auditory nerve. Kanamycin is less toxic. Since aminoglycosides are concentrated in the kidney, they may occasionally cause kidney damage. 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

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