Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats

Abstract

This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (θ) were obtained by analyzing Ficoll [mol.radius ( ae) 13–85 Å] in urine and plasma after 20 and 60 min I/R. Furthermore, θ for human serum albumin (HSA) was estimated using a tissue uptake technique after 20 and 60 min of I/R, while clearance of HSA compared with that for neutralized HSA (nHSA) was assessed after 20 min of I/R only. Glomerular filtration rate (GFR) was measured by [51Cr]EDTA and inulin. I/R reduced GFR and increased θ for Ficoll molecules of ae>55 Å and θ for albumin. θ for Ficoll vs. ae, analysed using a two-pore model, demonstrated that, despite increases in θ, the large-pore fractional ultrafiltration coefficient (αL) was unchanged after 20 min of I/R, owing to the decline in GFR, but increased after 60 min of I/R. However, the apparent αLfor albumin increased already after 20 min of I/R ( P < 0.005) and the nHSA/HSA clearance ratio was slightly reduced, possibly reflecting a diminished negative charge barrier. In conclusion, after 20 min of I/R, indications of a reduced charge selectivity were noted, while after 60 min of I/R, there was mainly a reduction in size selectivity, compatible with an increased formation of large pores.