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 (theta) were obtained by analyzing Ficoll [mol.radius (a(e)) 13-85 A] in urine and plasma after 20 and 60 min I/R. Furthermore, theta 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 theta for Ficoll molecules of a(e)>55 A and theta for albumin. theta for Ficoll vs. a(e), analysed using a two-pore model, demonstrated that, despite increases in theta, the large-pore fractional ultrafiltration coefficient (alpha(L)) 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 alpha(L) for 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.

Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

“…The to high-MW Ficolls (mol. radius Ͼ50 Å ) in sham animals in vivo in this experimental setting are extremely low and comparable to the fractional clearance of proteins of equivalent size (24,25). Sham animals for the ENDO groups (SHAM-120; n ϭ 7) received 120 min of constant NaCl infusion, 10 ml ⅐ kg Ϫ1 ⅐ h Ϫ1 , and, matching (in time) the infusion of LPS in the ENDO groups, a sham infusion of an extra 200 l NaCl during 30 min.…”

“…Sham animals for the ANA-5 group (SHAM-5; n ϭ 8) obtained a bolus of NaCl (250 l) 5 min before the Ficoll sieving assessment. Because there were no indications of changes in glomerular permeability between 5 and 120 min in the sham animals in the present experiments, nor in control rats in previous studies (24,25), we employed the glomerular sieving curves for the SHAM-120 animals as control curves for the ENDO-(60)/90 groups and those for SHAM-5 as controls for the ANA-40 group. In all sham groups, FITC-Ficoll (70/400) was infused intravenously using a protocol identical to those in the experimental groups.…”

“…In a recent study, we found that early diabetic microalbuminuria in rats was mainly related to size-selective changes in the glomerular barrier (25) and that charge alterations were just secondary. Also, the glomerular alterations following pronounced ischemia-reperfusion (I/R) injury could be mainly ascribed to size-selective changes, although after less severe I/R challenge, charge-selective alterations were also implicated (24).…”

Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo

“…Albumin permeability was not assessed due to high levels of denatured protein and free iodine ( 125 I) in all our current albumin preparations, leading to marked overestimations of the apparent for albumin. However, we have in previous experiments shown a near-complete coupling between alterations in for albumin and for high-molecular-weight Ficoll (50 -80Å) when glomerular permeability has been altered (3,9,46,47). Thus for Ficoll 50 -80Å seems to function as a good surrogate marker for glomerular albumin permeability across the GFB.…”

Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo

“…Sutton et al (43) demonstrated endothelial injury, cytoskeletal alteration, impaired cell-cell adhesion, and leakage of dextran from the renal microvasculature into the interstitium after bilateral renal pedicle occlusion (43). Using a rat renal pedicle occlusion model, Rippe et al (37) reported that renal permeability to Ficoll was increased by 60 min of unilateral renal ischemia, primarily large (Ͼ55 Å) Ficoll molecules. However, Andersson et al (2) found damage to both the size and charge barriers after mild (15 min) ischemia in isolated, perfused rat kidneys without morphological change as assessed by electron microscopy, suggesting that the glycocalyx (an endothelium-derived structure not imaged by electron microscopy) might be the source of barrier damage from ischemia.…”