Here we report two cases of isolated diffuse mesangial sclerosis (IDMS) with early onset end-stage renal failure. These female patients did not show abnormalities of the gonads or external genitalia. Direct sequencing of WT1 PCR products from genomic DNA identified WT1 mutations in exons 8 (366 Arg>His) and 9 (396 Asp>Tyr). These mutations have been reported previously in association with Denys-Drash syndrome (DDS) with early onset renal failure. Therefore we suggest that, at least in part, IDMS is a variant of DDS and that investigations for the WT1 mutations should be performed in IDMS patients. In cases with identified WT1 mutations, the same attention to tumor development should be required as in DDS patients, and karyotyping and serial abdominal ultrasonograms to evaluate the gonads and kidney are warranted.
Base Sequence ; DNA/chemistry/genetics ; DNA Mutational Analysis ; Fatal Outcome ; Female ; Glomerular Mesangium/*pathology ; Humans ; Infant ; Infant, Newborn ; *Mutation ; Nephrosclerosis/*genetics ; WT1 Proteins/*genetics

OBJECTIVE: To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction(UUO). METHODS: UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly divided into a sham-operated group(n=16), a UUO model group(n=24), and an enalapril treated group(n=24). The rats were treated with 10 mg/kg.d by gastric gavage in the enalapril treated group from 24 h before the operation, and the rats were treated with the identical dose of normal saline in the other 2 groups. The rats were sacrificed at 3,7,14, and 21 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expression of collagen I (Col I) was detected by real-time PCR, and the protein expression of connective tissue growth factor (CTGF) was detected by Western blot. RESULTS: The renal interstitial damage index, relative collagen area and the expression of Col I mRNA and CTGF in the renal tissues in the model group increased with the prolongation of obstruction. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, and inhibted the expression of Col I mRNA and CTGF. There was significant difference on day 3,7,and 14 (P<0.05), but not on day 21 (P>0.05). CONCLUSION Enalapril significantly attenuates renal interstitial fibrosis by supressing the expression of Col I mRNA and CTGF.
Animals ; Collagen Type I ; biosynthesis ; genetics ; Connective Tissue Growth Factor ; biosynthesis ; genetics ; Enalapril ; therapeutic use ; Male ; Nephritis, Interstitial ; etiology ; prevention & control ; Nephrosclerosis ; etiology ; prevention & control ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications

OBJECTIVE: To investigate the expression of P21 in renal interstitial fibrosis rats and the effect of enalapril on it. METHODS: Sprague Dawley rats were randomly divided into 3 groups: a sham operation group,a unilateral urethral obstruction group, and an enalapril treatment group. The expression of P21 in renal tubular epithelial cells on the process was detected by immunohistochemistry at different time spots (7, 14, 21 d after UUO, sham-surgery or enalapril treatment). The expression of p21 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Seven days after the surgery, significant differences were found in P21 expression between UUO and SOR renal tubular cells. With degree of interstitial fibrosis aggravating, P21 expression increased. Enalapril can inhibit its expression. CONCLUSION In the kidney of UUO rats, P21 expression increased and enalapril possessed significant inhibitory effects on the procedure. P21 may participate in the pathogenesis of renal tubule-interstitial fibrosis.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Enalapril ; pharmacology ; therapeutic use ; Kidney Tubules ; metabolism ; Male ; Nephrosclerosis ; drug therapy ; metabolism ; Proto-Oncogene Proteins p21(ras) ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications

OBJECTIVETo study the effect and mechanism of Kangxianling (KXL, a TCM herbal compound) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO).

METHODSEighteen male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KXL group. Renal interstitial fibrosis model was established in rats by UUO. After rats were raised for additional 14 days, their body weight, serum levels of creatinine (SCr) and blood urea nitrogen (BUN) were analyzed. Then rats were sacrificed, their renal pathology examined by HE staining and PASM staining; expressions of transforming growth factor-beta1 (TGF-beta1), hepatocyte growth factor (HGF) mRNA, and a-smooth muscle actin (alpha-SMA), TGF-beta1 receptor I (TbetaR I), TGF-beta1 receptor II (TbetaR II) and hepatocyte growth factor receptor (C-Met) protein in kidney tissue were determined by RT-PCR and Western blotting respectively.

RESULTSSCr and BUN in the model group were significantly higher than those in the sham operated group (P <0.05). Expressions of TGF-beta1 mRNA and a-SMA, TbetaR I , TbetaR II and C-Met protein in kidney tissue in the model group significantly up-regulated and mRNA expression of HGF significantly down-regulated, and obvious hyperplasia of the base member of glomeruli was seen. After intervention with KXL, BUN content significantly lowered, alpha-SMA, TbetaR I and TbetaR II protein expression decreased and HGF mRNA expression up-regulated significantly in the treated group, with slight pathological changes only shown as mild hyperplasia of the base member of glomeruli and renal tubules.

CONCLUSIONKXL could inhibit the protein expressions of a-SMA, TbetaR I , TbetaR II and increase the mRNA expression of HGF, which is a protective factor against renal fibrosis. Therefore, it is effective in alleviating the renal interstitial fibrosis and improving the renal function in UUO rats.

Animals ; Blotting, Western ; Drugs, Chinese Herbal ; therapeutic use ; Fibrosis ; prevention & control ; Hepatocyte Growth Factor ; biosynthesis ; genetics ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Nephritis, Interstitial ; etiology ; pathology ; prevention & control ; Nephrosclerosis ; pathology ; prevention & control ; Phytotherapy ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Ureteral Obstruction ; complications

OBJECTIVE: To explore the effect of p27 in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats, and to examine the expression changes of p27 after enalapril intervention and to interpret the anti-fibrotic mechanism. METHODS: Ninety rats were randomly divided into the sham-operated group (SOR), UUO group,and UUO+enalapril treatment group [enalapril: 10 mg/(kg.d)]. The rats of each group were respectively sacrificed on 7, 14, 21 days post-operatively. The renal pathological changes were dynamically observed by HE. The expression and dynamic changes of p27 were detected by immunohistochemistry. The level of p27 mRNA were detected by RT-PCR. RESULTS: The expression of p27 in renal tubular epithelial cells and p27 mRNA were strongly positive in the SOR group. With degree of interstitial fibrosis aggravating, the expression of p27 mRNA was gradually reducing. Enalapril could improve the expression of p27 on the 14th and 21st days after the UUO. CONCLUSION (1) This study supports a causative role of p27 in the formation of fibrosis of renal mesenchyme in rats with UUO. (2) The anti-fibrotic mechanism of enalapril is partly the improvement of p27 expression.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Cyclin-Dependent Kinase Inhibitor p27 ; biosynthesis ; genetics ; Enalapril ; pharmacology ; therapeutic use ; Female ; Kidney Tubules ; metabolism ; Nephrosclerosis ; drug therapy ; etiology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications