Cystic fibrosis, aminoglycoside treatment and acute renal failure: the not so gentle micin

Abstract

Aminoglycosides have a wide spectrum of gramnegative anti-bacterial activities and are available at low cost, which makes them commonly used drugs, especially for patients with cystic fibrosis (CF), who often suffer from chronic lung infections from Pseudomonas aeruginosa. Unfortunately, this treatment seems to have resulted in an increased incidence of acute renal failure (ARF) in patients with CF. A recent case-control study investigated risk factors for ARF in CF patients and suggested intravenous use of gentamicin as the prime culprit. Moreover, in most cases, at least one other risk factor, such as CF-related diabetes, pre-existing renal failure, dehydration or concurrent use of other nephrotoxic drugs, was present. We comment on the renal handling of aminoglycosides and the possible mechanisms of toxicity, as well as strategies for risk minimisation.

Specificity and Promiscuity at the Branch Point in Gentamicin Biosynthesis

“…It also shows promise as a lead for treatment of inherited diseases associated with premature stop codons (Hainrichson et al., 2008; Linde and Kerem, 2008) and acts as a sensitizing agent for NCI-H460 lung cancer cells, increasing the efficacy of various anticancer agents (Cuccarese et al., 2013). Unfortunately, these vital drugs entail a serious risk of kidney damage and hearing loss (Bockenhauer et al., 2009). Most studies on the mechanisms of gentamicin toxicity have used the commercial mixture, despite evidence that an individual component of the gentamicin mixture may have lower toxicity (Sandoval et al., 2006; Kobayashi et al., 2008).…”

An infant with alternating metabolic acidosis and alkalosis: answer

“…Despite many newly developed antibiotics, aminoglycosides remain an significant drug of choice in many infections, due to retained activity against most Gram-negative strains [10,11]. AKI in CF has been primarily associated with heavy antibiotic use [9], with the mechanism of injury being drug accumulation in epithelial cells [12]. Furthermore, aminoglycoside-induced nephrotoxicity normally manifests as non-oliguric renal failure [13].…”

“…Additionally, gentamicin could have been responsible, alone or in combination with dehydration, in the development of AKI. Nephrotoxic effects of gentamicin have been previously documented [8], and it is identified as the primary cause of AKI in CF patients [9]. Despite many newly developed antibiotics, aminoglycosides remain an significant drug of choice in many infections, due to retained activity against most Gram-negative strains [10,11].…”

Accidental and iatrogenic causes of acute kidney injury

“…The mechanism for the polyuric renal failure is thought to be decreased proximal tubule fluid resorption secondary to extensive tubular cell necrosis and decreased papillary solute concentration from mechanisms that are unknown [24]. Other renal injuries that have been described with aminoglycoside use include acute interstitial nephritis and electrolyte imbalances such as Fanconi-like syndromes and a Bartter-like syndrome [28–32]. …”