Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats.
Progression of renal damage after relief of unilateral ureteral obstruction (UUO) has been demonstrated, especially in neonatal rats. We evaluated renal function and renal damage after relief of 3-day UUO in five groups of adult rats: group 1, no treatment; group 2, 3-day UUO; groups 3-5, 3-day UUO followed by relief; group 3, 7-day relief; group 4, 14-day relief; and group 5, 28-day relief. Glomerular filtration rate (GFR), renal blood flow (RBF), tissue transforming growth factor-beta (TGF-beta), interstitial fibrosis and fibroblast expression, tubular apoptosis, macrophage infiltration, expression of nitric oxide synthases (NOS), and urinary nitrate/nitrite (NO(2)/NO(3)) were evaluated. RBF and GFR were decreased to <10% of baseline by 3 days of UUO. GFR and RBF in a previously obstructed kidney (POK) returned to baseline by 14 days after relief. Both tissue TGF-beta(1) and interstitial fibrosis were significantly higher in POK of groups 3-5 compared with groups 1 and 2 . In group 5, the numbers of infiltrating macrophages, fibroblasts, and apoptotic tubular cells were higher in POK compared with group 1. Urinary NO(2)/NO(3) was significantly higher than baseline from 3 to 27 days after relief of UUO. Expression of NOS isoforms was increased in tubules. As interstitial fibrosis contributes to decreased renal function, these results suggest that the acute recovery in function may be compromised in the long term by the progressive renal fibrosis which was found. Furthermore, pharmacological intervention at the time of relief of UUO, targeted to fibrotic processes, may contribute to long-term recovery of renal function.
Ito
Keiichi
K
Institute of Pediatric Urology, Department of Urology, Children's Hospital of New York, NY, USA.
Chen
Jie
J
El Chaar
Maher
M
Stern
Joshua M
JM
Seshan
Surya V
SV
Khodadadian
Jonathan J
JJ
Richardson
Ingride
I
Hyman
Michael J
MJ
Vaughan
E Darracott
ED
Poppas
Dix P
DP
Felsen
Diane
D
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001783:Blood Flow Velocity; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014517:Ureteral Obstruction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat