Faculty Collaboration Database

Correlation between cyclosporine-induced nephrotoxicity in reduced nephron mass and expression of kidney injury molecule-1 and aquaporin-2 gene. Transplant Proc 2005 Dec;37(10):4254-8

Date

01/03/2006

Pubmed ID

16387092

DOI

10.1016/j.transproceed.2005.10.025

Scopus ID

2-s2.0-29544442641 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Sirolimus (SRL) has been shown to exacerbate cyclosporine (CsA)-induced nephrotoxicity. The expression of the kidney injury molecule-1 (KIM-1) is markedly upregulated in the postischemic rat kidney. We sought to correlate drug-induced nephrotoxicity and the expression of KIM-1 and aquaporin-2 (AQP-2) in male PVG rats with 2 kidneys (2K), 1 kidney (1K), and half a kidney (1/2K) treated with SRL alone, CsA alone, or a combination of both (SRL-CsA). After 7 days of treatment, the 2K group treated with SRL-CsA showed a significant decrease in creatinine clearance compared with the 2K SRL alone and 2K CsA alone groups (1.2 vs 2.47 vs 2.46 mL/min; P < .001). There was a trend toward deterioration of creatinine clearance in the 1K and 1/2K groups treated with SRL-CsA. The KIM-1 expression in the 2K SRL-CsA group was significantly upregulated compared with that in the 2K SRL alone and 2K CsA alone groups (P = .02). The AQP-2 expression was comparable in the 3 groups. After 1 week of treatment washout, the 2K, 1K, and 1/2K groups treated with SRL alone demonstrated a significantly higher creatinine clearance rate than did the groups treated with SRL-CsA (P = .04, P = .02, and P = .004). The expression of KIM-1 and AQP-2 was similar among the treatment groups. SRL-CsA-induced nephrotoxicity resulted in overexpression of KIM-1, suggesting injury to the proximal tubule. Treatment with SRL alone may enable earlier reversal of tubular injury.

Author List

Hong ME, Hong JC, Stepkowski S, Kahan BD

MESH terms used to index this publication - Major topics in bold

Animals
Aquaporin 2
Cell Adhesion Molecules
Cyclosporine
Gene Expression Regulation
Kidney
Membrane Proteins
Models, Animal
Nephrons
Polymerase Chain Reaction
RNA
Rats
Rats, Inbred Strains
Reverse Transcriptase Polymerase Chain Reaction