Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Abstract

Ischemia-reperfusion injury conditions short-term and longterm graft function. The effects of the inversion of K + and N a + concentrations and substitution with polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW) solution were evaluated in isolated perfused rat kidneys and in autotransplanted pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW or Na-PEG UW solutions (IGL-I solution). Fractional sodium reabsorption and glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1 solution than those preserved in K-UW solution. In the pig model the left kidney was harvested and preserved in K-UW or IGL-1 solution for 24 h and then transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1 solution showed a better function and a significant reduction of MHC class I1 expression, cellular apoptosis and interstitial fibrosis.In conclusion, kidneys preserved in IGL-I solution tolerated ischemia/ reperfusion injury better than those preserved in K-UW solution.

Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

“…The presence of 1 g/L of PEG35000 stabilized the DPPC monolayer in the gaseous phase more strongly than PEG20000. This could be in agreement with the higher effectiveness of PEG35000 against cold-induced injuries observed in our cellular preservation model and also with the higher protection of PEG35000 observed during organ transplantation [3,4,11].…”

“…The inclusion of hydroxyethyl starch (HES) in the so-called University of Wisconsin (UW) solution, the standard preservation solution used in transplantation, has become increasingly controversial, and it has been suggested that HES could be efficiently replaced by polyethylene glycols (PEGs) [1,2]. Recent reports have shown that substituting HES by a 35,000 Da PEG (PEG35000) in an extracellular UW-like solution (IGL-1®) improved rat liver viability or pig kidney function [3,4]. In addition, our group has previously demonstrated in an auto-transplanted pig kidney model the beneficial effect on early and long-term cold ischemia-reperfusion injury of a saline solution with a composition mimicking an extracellular milieu and containing a 20,000 Da PEG (PEG20000) [5].…”

Protective Effect of PEG 35 000 Da on Renal Cells: Paradoxical Activation of JNK Signaling Pathway During Cold Storage

“…Other studies which have found that some PEG (8000 and 20 000 Da) improved other organs preservation suggested that PEG may be a valuable additive to a possible multiple organ liquid (28,29). In addition, recent reports showed that substituting PEG35 (1 g/L) for hydroxyethyl starch in an extracellular UW-like solution (IGL-1) improved rat liver viability or pig kidney function (20,30). Unexpectedly, we found that IGL-1 was inadequate for 24 h cell preservation whereas PEG 35 000 Da Protection in Kidney Cell Preservation adding only as little as 1 g/L of PEG35 in a very simple extracellular-type solution preserved more than 80% against cell death.…”

IGL‐1 solution in kidney transplantation: first multi‐center study

“…In addition, PEG induces a significant reduction of MHC class II expression on the cell surfaces, which plays an important role in ischemia/reperfusion injury as it enhances graft immunogenicity. There is a clear correlation between the degree of overexpression of MHC class II and CD4+ infiltrating cells, peritubular expression of VCAM‐1 and development of interstitial fibrosis (5, 6, 8).…”