Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Nov;37(11):2496–2499. doi: 10.1128/aac.37.11.2496

Use of human renal proximal tubule cell cultures for studying foscarnet-induced nephrotoxicity in vitro.

A L Trifillis 1, X Cui 1, G L Drusano 1
PMCID: PMC192418  PMID: 8285643

Abstract

Foscarnet is an antiviral agent used for the treatment of cytomegalovirus retinitis and acyclovir-resistant herpes simplex virus infections in AIDS patients. Renal impairment has been reported for many patients treated with foscarnet. We have studied the effects of foscarnet on the viability (estimated by neutral red inclusion) and ultrastructure of cultures of human renal proximal tubule cells (HRPTC) isolated from the kidneys of five cadavers and cultured. The degree of foscarnet-induced toxicity was dose dependent and varied among the HRPTC cultures. The data obtained by using the in vitro system of HRPTC mimic the data of the clinical trials in that there is a dose-dependent individual variation among human cases in response to foscarnet treatment. Thus, these cultures are extremely well-suited to investigations of the mechanism of toxicity at the subcellular level.

Full text

PDF
2496

Images in this article

2498Image
on p.2498

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borenfreund E., Puerner J. A. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett. 1985 Feb-Mar;24(2-3):119–124. doi: 10.1016/0378-4274(85)90046-3. [DOI] [PubMed] [Google Scholar]
  2. Chatterjee S., Trifillis A. L., Regec A. L. Biochemical and morphological effects of gentamicin in human proximal tubular cells: effects on lipid and lipoprotein metabolism. Biochem Cell Biol. 1987 Dec;65(12):1049–1056. doi: 10.1139/o87-137. [DOI] [PubMed] [Google Scholar]
  3. Chrisp P., Clissold S. P. Foscarnet. A review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs. 1991 Jan;41(1):104–129. doi: 10.2165/00003495-199141010-00009. [DOI] [PubMed] [Google Scholar]
  4. Drew W. L. Cytomegalovirus infection in patients with AIDS. Clin Infect Dis. 1992 Feb;14(2):608–615. doi: 10.1093/clinids/14.2.608-a. [DOI] [PubMed] [Google Scholar]
  5. Hochster H., Dieterich D., Bozzette S., Reichman R. C., Connor J. D., Liebes L., Sonke R. L., Spector S. A., Valentine F., Pettinelli C. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study. Ann Intern Med. 1990 Jul 15;113(2):111–117. doi: 10.7326/0003-4819-113-2-111. [DOI] [PubMed] [Google Scholar]
  6. Jacobson M. A. Review of the toxicities of foscarnet. J Acquir Immune Defic Syndr. 1992;5 (Suppl 1):S11–S17. [PubMed] [Google Scholar]
  7. Regec A. L., Trifillis A. L., Trump B. F. The effect of gentamicin on human renal proximal tubular cells. Toxicol Pathol. 1986;14(2):238–241. doi: 10.1177/019262338601400213. [DOI] [PubMed] [Google Scholar]
  8. Regec A. L., Trump B. F., Trifillis A. L. Effect of gentamicin on the lysosomal system of cultured human proximal tubular cells. Endocytotic activity, lysosomal pH and membrane fragility. Biochem Pharmacol. 1989 Aug 1;38(15):2527–2534. doi: 10.1016/0006-2952(89)90098-1. [DOI] [PubMed] [Google Scholar]
  9. Trifillis A. L., Kahng M. W. Effect of cyclosporine A on cultured human kidney cells: lipid peroxidation and cytosolic calcium. Transplant Proc. 1988 Jun;20(3 Suppl 3):717–721. [PubMed] [Google Scholar]
  10. Trifillis A. L., Regec A. L., Trump B. F. Isolation, culture and characterization of human renal tubular cells. J Urol. 1985 Feb;133(2):324–329. doi: 10.1016/s0022-5347(17)48932-4. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES