Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease,its prevalence ranges from 1 in 1 000 to 1 in 400.Two genes responsible for ADPKD, PKD 1 and PKD 2,were cloned in 1994 and 1996 respectively. Many researches have been done and great progress has been made on ADPKD.Current hot issues in this area included the structures and functions of polycystin 1 and polycystin 2,the role of cilia on polycystic kidney disease(PKD),the relationship between polycystins and the vascular abnormalities,the image evaluation of PKD,the effects of blocking RAS on slowing down the PKD progression and the treatment prospects for ADPKD. This paper focused on some issues and their implications for the diagnosis and treatment of PKD.

Objective To explore the autocrine mechanism of hepatocyte growth factor (HGF) and its receptor c-MET distribution in autosomal dominant polycystic kidney disease (ADPKD) cyst-lining epithelial cells. Methods The concentration of HGF was examined with ELISA in ADPKD patients' cystic fluid, serum and cultured media of cyst-lining epithelial cells. The expression of HGF and c-MET mRNA and protein in cyst-lining epithelial cells was detected by RT-PCR, in-situ hybridization, Western blotting, immunohistochemical analysis and computer image analysis. Results The concentration of HGF in ADPKD non-dialyzed patients'cystic fluid was much higher than that in ADPKD patients' serum [(8. 61?0. 07)ng/ml vs (0.26?0.05) ng/ml, P

Objective To study the expression of extracellular matrix and polycystin-1 in ADPKD and their relation to cyst formation. Methods The expression of polycystin-1, fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen were analysed in the normal kidney, fetal kidney and polycystic renal tissue by using immunohistochemical technique. Results The expression Of fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen increased in polycystic renal tissue compared with normal kidney. The basement membrane lining cysts was markedly thickened. Type Ⅰ collagen was detected in the interstitium between cysts. Laminin, fibronectin and type Ⅳ collagen were localized in cyst basement membrane. The expression of polycystin-1 increased in polycystic renal tissue. The expression of extracellular matrix had significant correlation with the expression of polycystin-1. Conclusion The abnormal expressions of extracellular matrix and polycystin-1 exist in ADPKD. Abnormal expression of polycystin-1 may result in the alterations of extracellular matrix that is related to cyst formation.

Objective: To study the influence of recombinant human hepatocyte growth factor (rhHGF) on proliferation and extracellular matrix synthesis of autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells in vitro . Methods: The effects of different concentration rhHGF (0.5,1,2.5,5 ng/ml)in 48 h and the optimal concentration rhHGF of different time (24,48,72 h ) on proliferation of ADPKD cyst lining epithelial cell lines were observed by the incorporation of 3H TdR, and synthesis of collagen and laminin were respectively observed by the incorporation of 3H proline and radioimmunoassay. Results: rhHGF stimulated the proliferation of ADPKD cyst lining epithelial cells and synthesis of collagen and laminin,the optimal concentration and time of rhHGF were 1 ng/ml and 48 h. Conclusion: rhHGF can significantly stimulate ADPKD cyst lining epithelial cells proliferation and extracellular matrix synthesis in vitro . [

Objective: To study the effect of N (4 hydroxyphenyl) retinamide (4 HPR) on apoptosis of cyst lining epithelial cells in autosomal dominant polycystic kidney disease (ADPKD).Methods: The proliferation of ADPKD cyst lining epithelial cells was detected by MTT assay after stimulated by 1,2.5,5 and 10 ?mol/L 4 HPR for 24,48,72 and 96 h respectively.The effect of 4 HPR on the survival rate of cells stimulated by HGF was analyzed with trypan blue staining.The effect of 4 HPR on the apoptotic rate of cyst lining epithelial cells stimulated by HGF was detected with DNA laddering and cell staining with fluorescent dye Hoechst 33342.The expression of HGF and c Myc protein was examined by immunohistochemical staining and semi quantitative analysis in cyst lining epithelial cells stimulated by 4 HPR.Results: Compared with control group,4 HPR inhibited the proliferation of ADPKD cyst lining epithelial cells in a dose and time dependent manner.The most remarkable inhibition effect was observed by 5 or 10 ?mol/L 4 HPR for 96 h ( P

Objective:To study the effects of recombinant human hepatocyte growth factor (rhHGF) on the synthesis of extracellular matrix (ECM) and matrix metalloproteinases and tissue inhibitor of metalloproteinases in autosomal dominant polycystic kidney disease (ADPKD) cyst lining epithelial cells.Methods:The synthesis of laminin (LN) and aminoterminal propeptide of type Ⅲ procollagen (PⅢNP) in ADPKD cyst lining epithelial cells stimulated by rhHGF was examined with radioimmunoassay.The synthesis of type Ⅳ collagen (ColⅣ) was analyzed with ELISA.The mRNA expression of transforming growth factor ? 1 (TGF? 1),matrix metalloproteinases 2 (MMP 2),tissue inhibitor of metalloproteinases 1 (TIMP 1) and TIMP 2 in rhHGF stimulated cyst lining epithelial cells were detected by RT PCR.MMP 2 protein expression was examined with Western blotting and MMP 2 activity was analyzed by gelatin zymography in supernatant of cyst lining epithelial cells stimulated by rhHGF.Results:In rhHGF group and rhHGF+ anti TGF? 1 antibody group,the synthesis of LN and ColⅣ were markedly increased.There was no significant difference in the synthesis of LN and ColⅣ between the 2 groups.Among control group,rhHGF group,rhHGF+ anti HGF antibody group and rhHGF+ anti TGF? 1 antibody group,no significant difference in the synthesis of PⅢNP was found.No significant difference was found in the expression level of TGF? 1 mRNA in cyst lining epithelial cells among control group,rhHGF group and rhHGF+anti HGF antibody group.Compared with control group,MMP 2 mRNA expression in ADPKD cyst lining epithelial cells was significantly increased and TIMP 1 mRNA and TIMP 2 mRNA expression were significantly decreased in rhHGF group.Furthermore,MMP 2 protein expression and MMP 2 activity in supernatant of cyst lining epithelial cells also greatly increased.Conclusion:HGF stimulates the synthesis of LN and ColⅣ.HGF up regulates MMP 2 expression while HGF down regulates TIMP 1 and TIMP 2 expression in ADPKD cyst lining epithelial cells.All these changes may involve in the initiation and progression of ADPKD cysts.

ObjectiveTo study the outcome of renal transplantation in polycystic kidney disease (PKD) and its influencing factors.MethodsFrom 1978 to 2002, 46 PKD patients undergoing renal transplantation (PKD group) and 46 cases of other diseases (non-diabetic nephropathy;control group) were retrospectively analyzed. Patient/renal survival rate (1, 3 and 5 years after re nal transplantation) and postoperative complications were evaluated.ResultsA comparable overall patient (1, 3 and 5 years: 95.7?% , 91.3?% , 91.3 ?% PKD vs 97.8?% , 95.7?% , 93.5?% controls) and transplant sur vival rate (1, 3 and 5 years: 93.5?% , 89.1?% , 87.0?% PKD vs 95 .7?% , 89.1?% , 87.0?% controls) was found in both groups. Infectious complications with the exception of urinary tract infections (UTIs: PKD 43.4 ?% vs 10.9?% ) were diagnosed in similar frequency in the graft recipien ts. PKD patients were significantly more affected by UTIs than the control group (P

Objective:To investigate and compare the effect and the possible mechanisms of 2 hypoxia-inducible factors(HIF) 1? and 2? on renal cell carcinoma(RCC) by RNA interference(RNAi) method.Methods: Chemically synthesized HIF-1? and HIF-2? RNAi were transfected into RCC cell line A498 by liposome transient transfection.Normal proximal tubule cell line HK-2 and A498 were separately treated with medium and liposome as controls.The expressions of VEGF,ET-1,bcl-2 and Ki67 were observed by RT-PCR or Western blot 24 h after RNAi.Cell apoptosis was detected by flow cytometry and fluorescence microscopy.Results: Expressions of HIF-1? and HIF-2? RNAi were higher in A498 than those in HK-2,and the 2 genes were successfully blocked after RNAi.HIF-1? RNAi resulted in a significant decrease of ET-1,bcl-2 and Ki67 expression,with increased apoptosis and necrosis of cells.HIF-2? RNAi only resulted in a decrease of VEGF.Conclusion: Both HIF-1? and HIF-2? play important roles in regulation of angiogenesis; moreover,HIF-1? might also regulate proliferation of tumor cells,possibly through regulating anti-apoptotic genes.It is implied the existance of different transcription regulation functions and gene combining sites between HIF-1? and HIF-2?.

Objective To study the quantitative method of determination of Fas ligand (FasL) and T-cell intracellular antigen-1 (TIA-1) in renal allografts and to evaluate its clinical significance. Methods The magnitude of intragraft FasL and TIA-1 mRNA was quantified by competitive PCR in 42 samples obtained to diagnose the etiology of graft dysfunction, and the results were expressed as the ratio of picograms of target gene to picograms of ?-actin, and were compared with the histopathogical diagnosis based on Banff criteria. Results Of all 42 samples, the transcripts were detectable in 11 for FasL and 27 for TIA-1. Intragraft expression of FasL and TIA-1 was significantly up-regulated in acute rejection group compared with chronic rejection group (P

Objective To report immune-reconstruction in two patients with acute radiation sickness due to 60Co radiation accident after stem cell transplantation.Methods Patient “A” and “B” were diagnosed as intestinal form of acute radiation sickness(ARS)and extremely severe degree bone marrow form of ARS,respectively.Peripheral blood stem cell transplantation was successfully performed in these two patients.During their whole disease course,absolute lymphcyte count,neutrophil leukocyte count,T-lymphocyte subsets,natural killer(NK),and immunoglobulin were sequentially determined.Results Immunoglobulin was decreased after irradiation without any recovery tendency after the transplantation.After irradiation,absolute lymphcyte count decreased rapidly,but recovered partially after the transplantation(maintained at 0.5?109/L).Neutrophilic leukocyte count rose rapidly to normal after the transplantation.NK was lowered obviously after irradiation,and it rapidly recovered to normal level after the transplantation,and maintained at a level higher than normal.After irradiation,the proportion of CD4/CD8 showed a transient rise,followed by an abrupt lowering.After the transplantation,it showed a tendency of elevation,but it did not recover to normal.Conclusions The tendency of lowering of immunoglobulin,lymphocyte count,NK cell count,and CD4/CD8 ratio indicate that there is a rapid deterioration of both cellular and humoral immunity after irradiation.Following the homogeneic peripheral blood transplantation,neutrophil count and NK cell count showed a rapid recovery,lymphocyte count and CD4/CD8 ratio also showed a tendency of slow elevation,but there is no sign of recovery of immunoglobulin.The results indicate that there is a faster recovery of cellular immunity.