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.
Adjunctive oral MPD therapy reduced the occurrence and/or severity of renal scarring after acute pyelonephritis in these hospitalized children who had a high risk of renal scar formation.
To investigate the incidence of acute pyelonephritis (APN) and renal scarring in children with febrile urinary tract infection (UTI), 191 of 216 (88%) children with their first episode of UTI received 99m Tc-dimercaptosuccinic acid renal single-photon emission computed tomography. They were investigated within 7 days of admission and were followed for 6 months. One hundred and six patients (49.1%) underwent a voiding cystourethrogram. The incidence of vesicoureteric reflux (VUR) in group I (≤1 year old) was 22%, group II (1-5 years old) 69%, and group III (5-17 years old) 44%. The overall incidence of APN in febrile UTI was 70% (male 66%, female 76%, P=0.110). Children had a higher incidence of APN than infants (P<0.05 in group I vs. II and group I vs. III). Of patients with APN, 57% (35/61) showed renal scar formation. VUR was found in 31%(24/78) of children with APN and 58% (14/24) of children with renal scar. In addition, children with high-grade VUR were more susceptible to APN and scar formation than those with low-grade VUR (P<0.05). Older children with a first febrile UTI had a higher incidence of APN than infants (≤1 year), and half of the children with APN developed a renal scar.
Quantitative analysis of acute DMSA renal SPECT findings is valuable in predicting renal fibrosis. The volume of an acute pyelonephritis lesion is useful in predicting the development of fibrosis.
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