In vitro systems for nephrotoxicity studies

A Jay Gandolfi, K. Brendel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A variety of in vitro systems, including the perfused kidney, microperfused nephron(s), cultured renal slices, renal tubule suspensions/cultures, isolated nephron components (glomeruli and tubule segments) and renal cell suspensions/cultures can be utilized to evaluate chemicals for their potential nephrotoxicity and mechanisms of action. These systems have varying degrees of relevance to the intact kidney or portions thereof; which model to use depends on the specific question asked. If maintenance of physiological flow conditions is important then only the perfused kidney (or tubule) can be used. If the toxicity can be studied in the absence of normal fluid flow, then the other systems may be utilized. Kidney subfractions also have the advantage of multiple biological units that can be examined simultaneously and separately. Closely defined renal slice systems allow for enrichment and evaluation of multiple target cells within the slice. Suspensions or cultures of nephron subfractions are now frequently used to assess the potency and/or mechanism of renal toxins. Disadvantages include the utilization of collagenase, which scars cell and basement membranes and affects membrane transport proteins, which leads to inadequate maintenance of transport mechanisms. Isolation of tubule segments (P1, P2, P3), allows site-specific toxicity studies. Lastly, there has been a dramatic increase in renal cell culture to study toxic events in the kidney. Because of the multiple cell types, minimal availability of specific cell markers, and de-differentiation phenomena, this technique should be used with caution. These in vitro systems have allowed us to examine the role of transport and biotransformation, and to compare potency and mechanism of nephrotoxic chemicals. Although in vitro systems cannot totally duplicate or replace in vivo toxicity studies, they are a very useful and valuable complement.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalToxicology in Vitro
Volume4
Issue number4-5
DOIs
StatePublished - 1990

Fingerprint

Toxicity
Suspensions
Kidney
Membrane Transport Proteins
Poisons
Collagenases
Cell membranes
Nephrons
Cell culture
Flow of fluids
Availability
Cell Culture Techniques
Maintenance
In Vitro Techniques
Kidney Tubules
Differentiation Antigens
Biotransformation
Basement Membrane
Cicatrix
Cell Membrane

ASJC Scopus subject areas

  • Toxicology

Cite this

In vitro systems for nephrotoxicity studies. / Gandolfi, A Jay; Brendel, K.

In: Toxicology in Vitro, Vol. 4, No. 4-5, 1990, p. 337-345.

Research output: Contribution to journalArticle

Gandolfi, A Jay ; Brendel, K. / In vitro systems for nephrotoxicity studies. In: Toxicology in Vitro. 1990 ; Vol. 4, No. 4-5. pp. 337-345.
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