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Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
07:06

Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule

Published on: May 9, 2025

Studies of nephrotoxic agents in an improved renal proximal tubule system

C A Tyson1, J E Dabbs, P M Cohen

  • 1SRI International, Menlo Park, CA 94025, USA.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|August 13, 2010
PubMed

Insights

This study demonstrates that renal proximal tubule fragments (RPT) effectively model chemical-induced nephrotoxicity. The RPT system accurately predicts in vivo responses to various nephrotoxins.

Area of Science:

  • Toxicology
  • Renal Physiology
  • Biochemistry

Background:

  • Nephrotoxicity studies require reliable models for mechanistic investigations and screening.
  • Existing models may not fully capture the complexity of chemical interactions within the kidney.

Purpose of the Study:

  • To evaluate isolated rat renal proximal tubule (RPT) fragments as a model for studying chemical-induced nephrotoxicity.
  • To assess the RPT system's utility in predicting in vivo responses to known nephrotoxins.

Main Methods:

  • Preparation of RPT fragments from male F-344 rats using deferoxamine/collagenase perfusion.
  • Incubation of RPT fragments with nephrotoxins including chloroform, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), cephalosporins, acetaminophen, and p-aminophenol.
  • Measurement of oxygen consumption, lactate dehydrogenase (LDH) release, and enzyme activities (alkaline phosphatase, gamma-glutamyltranspeptidase).

Main Results:

  • Chloroform and DCVC decreased oxygen consumption and increased LDH release in RPT fragments.
  • DCVC exhibited higher cytotoxicity to RPT than to rat hepatocytes.
  • Cephalosporins reduced alkaline phosphatase activity, with potency ratios aligning with in vivo data at higher RPT concentrations.
  • Acetaminophen and p-aminophenol induced LDH release and inhibited mitochondrial respiration without affecting alkaline phosphatase.

Conclusions:

  • The RPT fragment system serves as a valuable model for mechanistic studies of chemical nephrotoxicity.
  • Results obtained from the RPT model generally correlate well with established in vivo responses.
  • This model shows promise for screening and understanding the toxicological effects of chemicals on the kidney.

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