Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats

Abstract

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.

Effect of combination therapy with enalapril and the TGF-β antagonist 1D11 in unilateral ureteral obstruction

“…Sprague-Dawley rats (n ϭ 8 per group) underwent unilateral ureteral ligation with 4 -0 silk suture through a midline abdominal incision under sterile conditions as routinely carried out in our lab (8). Enalapril was administered in drinking water at 200 mg/l.…”

“…Immunohistochemical analyses for macrophages were carried out using a monoclonal antibody to ED-1 (Serotec) as previously described (8). Macrophages were counted in 10 high-power fields (ϫ400) by two different independent investigators in a blinded fashion.…”

“…We also analyzed tissue for the presence of fibroblasts using immunohistochemistry, as previously described (8). The antibody utilized was DAKO S100-A4 (1:100 dilution).…”

Characterization of renal interstitial fibroblast-specific protein 1/S100A4-positive cells in healthy and inflamed rodent kidneys

“…Indeed, the induction of FSP1 in injured proximal tubules has been taken as evidence of EMT (Chai et al 2003;Ito et al 2004;Iwano et al 2002;Okada et al 2000;Strutz and Neilson 2003). In addition to the antibodies against FSP1 (Strutz and Neilson 2003), willingly provided by F. Strutz, we also used a commercial antibody against S100A4.…”

Evaluation of hydronephrotic kidney parenchymal density by non-contrast multislice computed tomography

“…Hydronephrosis resulting from an obstruction of the ureter, commonly encountered in urological practice, may cause progressive injury in renal parenchyma and lead to permanent loss of renal function if not treated Ito et al, 2004). Urinary tract obstruction can develop in different age groups for different reasons.…”