Ischemic acute renal failure: Long-term histology of cell and matrix changes in the rat

Citation
Jm. Forbes et al., Ischemic acute renal failure: Long-term histology of cell and matrix changes in the rat, KIDNEY INT, 57(6), 2000, pp. 2375-2385
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
0085-2538 → ACNP
Volume
57
Issue
6
Year of publication
2000
Pages
2375 - 2385
Database
ISI
SICI code
0085-2538(200006)57:6<2375:IARFLH>2.0.ZU;2-3
Abstract
Background. The cellular infiltration and matrix accumulation accompanying acute renal ischemia and reperfusion have been frequently noted but poorly defined. The long-term consequences of ischemia may irreversibly damage the kidney. Methods. Female Sprague-Dawley rats (200 g) underwent unilateral nephrectom y. After five days, the left renal pedicle was occluded for 45 minutes. Ani mals were sacrificed at 0, 1, 2, 4, 8, 16, 32, 64, and 180 days postischemi a (N = 6). Immunohistochemistry for monocytes/macrophages (Mo/M phi, ED-1), myofibroblasts [alpha-smooth muscle actin (alpha-SMA)], collagen III and T V, matrix metalloproteinase-2 (MMP-2) and proliferating cell nuclear antige n (PCNA) and terminal dUTP nick end labeling (TUNEL) were performed. Results. Kidney weights of postischemic animals were increased at all time points (postischemic to controls, 1.47 +/- 0.21 to 0.94 +/- 0.12 g at day 8 ; 1.49 +/- 0.20 to 1.27 +/- 0.13 g at day 64; and 1.86 +/- 0.1 to 1.24 +/- 0.2 g at day 180). Serum creatinine values increased to 0.42 +/- 0.10 mmol/ L at day 2 but returned to control levels by day 8 (0.05 mmol/L). Glomerula r collagen IV was decreased from 2 to 16 days postischemia, which was accom panied by an increase in MMP-2. The fractional area of the interstitium was greatest at day 8 (19.55 +/- 0.91% compared with day 0 at 8.08 +/- 0.27%), with a second increase observed at day 180 (16.61 +/- 0.70%). Interstitial Mo/M phi increased postischemia from days 2 through 8 (8.84 +/- 2.12 to 13 3.32 +/- 14.04 per 0.91 mm(2)) and then decreased. Myofibroblasts prolifera ted locally (PCNA double labeling was demonstrated), and increased numbers were found from days 2 through 16 (maximal at day 8, 26.96 +/- 3.04%, compa red with day 0, 0.88 +/- 0.11%). In the postischemic groups, collagen IV in creased to day 8 (20.84 +/- 1.30%), but then decreased to below control val ues at day 64 (2.22 +/- 0.15%) before returning to normal by day 180. Inter stitial collagen III increased to 8 days (0.45 +/- 0.07% to 2.55 +/- 0.36%) and then decreased to control levels by day 32, but showed a marked increa se to approximately 6% at days 64 and 180. Cellular proliferation (PCNA) wa s maximal at days 2 and 4 (affecting tubule cells and myofibroblasts but no t macrophages). Apoptosis was maximal at day 8 (in both interstitial and tu bule cells) in the postischemic groups. Conclusion. Marked changes in the accumulation of Mo/M phi, MF, and collage n IV were found in this model of ischemic acute renal failure. The reversib ility of functional and structural changes is in marked contrast to that fo und in progressive disease. The increases observed for collagen III at 64 a nd 180 days postischemia suggest that in the long term, however, further ch ronic structural changes may be observed.