Clinical strategies: renal dialysis

Dr Ryan Hamilton discusses the changes that are made to aminoglycoside dosing in patients with advanced renal failure who are receiving haemodialysis.

In renal failure, the clearance half-life of aminoglycosides is extended to such a length (i.e. 40-60 hours vs 2 hours for gentamicin) that it would take days, if not weeks, for serum concentrations to become low enough to allow another dose to be given safely. In the meantime, the concentrations will have dropped below effective levels but remain high enough to induce adverse effects.

Because aminoglycosides are relatively small hydrophilic molecules with minimal to no serum protein binding, they are easily filtered out of the blood using dialysis techniques, which are vital to the survival of patients with renal failure.

Haemodialysis and haemodiafiltration

In haemodialysis and haemodiafiltration, nearly all of the aminoglycoside circulating in the blood will be removed. Any redistributed from tissues into the blood during dialysis will also be removed. However, aminoglycosides residing within tissues will not be removed. Regardless, haemodialysis and haemodiafiltration filter out enough aminoglycoside molecules to make it safe to give further doses and re-attain effective concentrations to treat the infection. In practice, the dose of aminoglycoside is given after dialysis is finished and the dose is reduced (e.g. to 3 mg/kg for gentamicin) to avoid prolonged high-concentrations and accumulation, thus avoiding adverse effects.

Peritoneal dialysis

In peritoneal dialysis, the aminoglycoside is distributed from the blood into the peritoneal dialysate, as it would with other water compartments. Thus, when the dialysate is exchanged, a portion of the aminoglycosides are also removed. This technique is not as efficient at removing aminoglycosides as haemodialysis methods, so the subsequent doses are often reduced and dosing intervals are increased (e.g., 2-3 mg/kg gentamicin every 72 hours with regular TDM).