Y-Y Chiou | PubMed Health

PubMed2006

Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis.

Unilateral ureteral obstruction (UUO) is a well-characterized hydronephrosis model exhibiting interstitial inflammatory-cell infiltration and tubular dilatation followed by tubulointerstitial fibrosis of the obstructed kidney. Our recent report indicates that rapamycin is effective for 50% of transplant recipients with chronic allograft nephropathy. In this study, we investigate the effect of rapamycin on UUO-induced renal fibrosis. UUO or sham-operated rats were randomly assigned to rapamycin or vehicle and were killed on days 7 and 14 after UUO or sham operation. Rapamycin decreased cross-sectional and gross-morphology changes in the obstructed kidney significantly. Rapamycin markedly blunted the increase in weight of the obstructed kidney, obstructed kidney length, and the obstructed/non-obstructed kidney weight ratio (by 74.6, 42.8, and 61.6% on day 14, respectively, all P<0.01). The scores for tubular dilatation, interstitial volume, interstitial collagen deposition, and alpha-smooth muscle actin (alpha-SMA) after UUO were significantly reduced by rapamycin. Rapamycin also decreased the number of infiltrative anti-ED1-positive cells and the gene expression of transforming growth factor (TGF)-beta1 (84.8 and 80.2% on day 7) after UUO (both P<0.01). By double immunostaining and Western analysis, rapamycin blocked the TGF-beta1-induced loss of E-cadherin expression and de novo increase of the expression of alpha-SMA in a dose-dependent manner. In conclusion, rapamycin significantly attenuated tubulointerstitial damage in a UUO-induced rat model of renal fibrosis, suggesting that rapamycin may have the potential to delay the progression of tubulointerstitial renal fibrosis.

Animals↗

PubMed2002

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Acute Disease↗