Kidney-based in vitro models for drug-induced toxicity testing.

Area of Science:

• Nephrology
• Pharmacology
• Toxicology

Background:

• Kidney damage from drugs (drug-induced nephrotoxicity) is a significant issue in pharmacotherapy, accounting for up to 25% of serious adverse effects.
• Antimicrobials are a notable cause, contributing to one-third of these drug-induced kidney injuries.
• Existing in vitro assays often fail to predict in vivo toxicity due to inadequate models of the kidney's complex microenvironment.

Purpose of the Study:

• To review drug-induced kidney injuries.
• To detail relevant and translational biomarkers for assessing nephrotoxicity.
• To discuss advancements in 3D human renal cell cultures for improved toxicity prediction.

Main Methods:

• Literature review of drug-induced nephrotoxicity.
• Analysis of existing in vitro assay limitations.
• Exploration of novel 3D cell culture models like organoids and kidney-on-a-chip platforms.

Main Results:

• Drug-induced nephrotoxicity mechanisms include direct cellular damage, vascular effects, and crystal deposition.
• The kidney's complex microenvironment, including cell polarity and intercellular communication, is critical for predicting toxic responses.
• 3D culture models show promise in better replicating the in vivo kidney microenvironment.

Conclusions:

• Accurate prediction of drug-induced kidney injury requires models that preserve the kidney's microenvironment.
• Advancements in 3D renal cell cultures offer improved platforms for drug nephrotoxicity screening.
• Further research into biomarkers and advanced models is essential for developing safer drugs.