Pd45-12 intraoperative Mannitol Administration During Laparoscopic Donor Nephrectomy and Impact on Long-Term Graft Function

Abstract

molecules may be a promising approach to reverse renal fibrosis. The goal of this study is to test the use of the cell-signaling chemokine CXCL12 in reversing renal fibrosis in a cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis.METHODS: In this model, 30 adult female cats received an intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls (n[6/treatment condition). Kidney collagen content was quantified 4 months post CXCL12 or saline injection using Masson's Trichrome and Picrosirius Redstained renal collagen tissues. In additional pilot study, cats with I/R were assessed 30 minutes or 1 week post-CXCL12 injection for kidney expression of matrix metaloproteinase-1 (MMP-1), LOXL-2 (associated with collagen cross-linking) and CXCL12; using ELISA analysis of the I/R kidney.RESULTS: I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal (p<.05 vs. untreated) (Figure 1). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal (p<.001 vs. untreated) (Figure 1). Early changes in kidney (increased MMP-1) (increased CXCL12), and (decreased LOX-2) were not seen 4 months post CXCL12 injection.CONCLUSIONS: Local injection of recombinant CXCL12 reverses the formation of TIF in a dose dependent manner. Its early effects on molecules affecting collagen breakdown and cross-linking may alter collagen metabolism, resulting in reduced fibrosis. Additional mechanistic, long-term efficacy and safety studies are needed.