Solute carrier transporter and drug-related nephrotoxicity: the impact of proximal tubule cell models for preclinical research

• Published in: Expert opinion on drug metabolism & toxicology Vol. 10; no. 3; p. 395
• Main Authors: Fisel, Pascale, Renner, Olga, Nies, Anne T, Schwab, Matthias, Schaeffeler, Elke
• Format: Journal Article
• Language: English
• Published: England 01.03.2014
• Subjects: Animals; Cell Line; Epithelial Cells - cytology; Epithelial Cells - drug effects; Humans; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - pathology; Membrane Transport Proteins - drug effects; Membrane Transport Proteins - metabolism; Models, Theoretical
• ISSN: 1744-7607
• DOI: 10.1517/17425255.2014.876990

The final excretion step of several drugs is facilitated by membrane transporters of the Solute carrier (SLC) family expressed in the proximal tubules of the kidney. Membrane transporters contribute substantially to the pharmacokinetic profile of drugs and play important roles in drug-induced nephrotoxicity. Different cell models have been applied as tools for the assessment of nephrotoxic effects caused by drugs. This review gives an overview over clinically relevant SLC transporters involved in the renal elimination of drug agents and their specific role in drug-induced nephrotoxicity. Most widely applied cell models are described and their advantages and limitations are outlined. In vitro cell culture models (e.g., continuous and primary renal cell lines, polarized cell monolayers) represent valuable tools for early assessment of the nephrotoxic potential of drugs. Since SLC transporters contribute to drug excretion in a large part, in vitro cell culture models might be very helpful to study transport pathways and/or potential drug-drug interactions at an early stage of the drug development process to predict nephrotoxic effects.