Features of toxic nephropathy development during antibiotic therapy

Abstract

Scientist relevance. Antibacterials can have nephrotoxic effects because medicinal products of this class are primarily excreted by the kidneys.Aim. The study aimed to analyse literature data on the mechanisms, risk factors and specific features of toxic nephropathy development during antibiotic therapy.Discussion. The article considers mechanisms of development of acute interstitial nephritis, acute tubular necrosis, crystal deposits in the tubules, proximal or distal tubulopathy with electrolyte abnormalities during the use of antibiotics. Nephrotoxicity was shown to be most often associated with the use of aminoglycosides, beta-lactams, and vancomycin. The authors analysed the dependence of nephrotoxicity on antibacterial agent lipophilicity and drug–drug interactions. The main risk factors for developing nephropathy are older age; male sex; black race; hypovolaemia; arterial hypotension; angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs or their combinations; and individual genetic characteristics. Nephrotoxicity is associated with genetic characteristics of the systems responsible for metabolism and excretion of antibacterial products: cytochrome P450 isoenzymes, P-glycoprotein, multidrug resistance protein (MRP), multidrug and toxin extrusion (MATE), breast cancer resistance protein (BCRP), and organic anion transporters. Severe generalised infections change pharmacokinetic parameters of antibacterial products. This should be taken into account when prescribing the hydrophilic antibiotics that are excreted by tubular secretion and reabsorbed in the renal tubules.Conclusions. The study demonstrated the effectiveness of the method comprising a combination of dose adjustment based on therapeutic drug monitoring results and renal function monitoring for improving the safety of antibiotic therapy.

Keywords

• toxic nephropathy
• acute interstitial nephritis
• acute tubular necrosis
• adverse drug reactions
• antibiotics
• safety of pharmacotherapy