Relation of distal nephron changes to proximal tubular damage in uranyl acetate-induced acute renal failure in rats.
OBJECTIVE
To elucidate the pathophysiological roles of the changes of distal nephron in uranyl acetate (UA)-induced acute renal failure (ARF), we investigated the relation of changes of constituent molecules in distal nephron to proximal tubular damage and repair in UA-treated rats.


METHODS
ARF was induced in rats by intravenous injection of UA, and all rats received bromodeoxyuridine (BrdU) intraperitoneally 1 h before sacrifice.


RESULTS
Proximal tubular damage with necrosis appeared as early as day 2, mainly in the outer stripe of outer medulla and reached a peak level at day 5. Slight cellular damage was evident in the distal nephron as early as day 3, reaching a peak level around day 9. Immunoreactive BrdU- or vimentin-positive regenerating proximal tubules (PT) appeared at day 2 and regenerating PT relining was almost completed by day 7. Immunostaining for EGF, which was constitutively expressed in the thick ascending limb (TAL) and distal convoluted tubule (DCT), diminished significantly as early as day 2, when PT regeneration became evident, and remained below normal levels until day 21. In contrast, slight immunoreactivity for EGF was observed in regenerated PT accompanying brush-border formation mainly after day 9, suggesting newly expressed EGF might contribute to PT maturation. Lectin staining or immunostaining for representative constituent molecules of the thin descending limb, TAL, DCT and collecting duct demonstrated marked and transient reduction after day 5.


CONCLUSIONS
EGF was not associated with regenerating PT, but may be involved in the maturation of PT. Transient reduction in expression of constituent molecules of the distal nephron following the reduction in EGF could reflect dedifferentiation or phenotypic simplification during regenerative repair of PT in UA-induced ARF in rats.
Sun
Di Fei
DF
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Fujigaki
Yoshihide
Y
Fujimoto
Taiki
T
Goto
Tetsuo
T
Yonemura
Katsuhiko
K
Hishida
Akira
A
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D001972:Bromodeoxycytidine / Q000032:analysis; D004815:Epidermal Growth Factor / Q000032:analysis; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009336:Necrosis; D009399:Nephrons / Q000473:pathology*; D009942:Organometallic Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D014746:Vimentin / Q000032:analysis
D009942:Organometallic Compounds; D014746:Vimentin; D001972:Bromodeoxycytidine; C005460:uranyl acetate; D004815:Epidermal Growth Factor