Objective To analyze and compare the clinical characteristics of atherosclerotic renal artery stenosis (ARAS) and benign nephrosclerosis (BN) in order to distinguish the ARAS from BN. Method A retrospective study was performed on 82 hypertensive patients with renal injury. Patients were divided into BN and ARAS group according to renal artery doppler scanning. The clinical date such as age， gender， family medical history， blood pressure， urine protein excretion， serum indexes，eyeground and blood vessel morphology were analyzed. Results Ischemic renal disease (IRD) was identified in 17/82 patients (20.7%)， among whom 13 (13/82， 15.9% ) exhibited ARAS. 17/19 (89.5%) patients were correctly identified by doppler ultrasound scanning. Between ARAS and BN， there were significant differences in age， family medical history， course of hypertension ， body mass index， smoking， total cholesterol， serum glucose， left ventricle mass index， kidney size. Renal artery duplex scanning showed significant differences in renal-aortic ratio， peak systolic velocity， end-diastolic velocity， resistive index of arteries in ARAS versus BN. Conclusions BN diagnosed clinically can not exclude the possibility of ARAS， which may also exhibit an insidious nature . Color doppler ultrasonography is the best screening method with a predictive value. Obesity， smoking， hyperlipidemia and hyperglycemia are risk factors of ARAS.

Objective To evaluate the prognostic result of renal function on atherosclerotic renal artery stenosis (ARAS) patients after revascularization and medication therapy. Methods The clinical data of 132 ARAS patients diagnosed by renal angiography were analysed. For comparing the differences of glomerular filtration rate (GFR) between revascularization and medication therapy， 88 patients with unilateral ARAS were divided into two groups: ≤70 and>70 years old， meanwhile， according to GFR， these patients were divided into ≥60 and <60 ml/min groups. Forty-four patients with bilateral ARAS were divided into bilateral， unilateral and non-revascularization three groups according to the treatment， and differences were compared among these three groups. Results In unilateral ARAS patients， the GFR variety after 1-year revascularization was better than that of medication therapy in ≤70 years old group and GFR≥60 ml/min group. There were no differences of GFR variety between revascularization and medication in > 70 years old group and GFR < 60 ml/min group. In 44 bilateral ARAS patients， the GFR variety was better in bilateral revascularization group than that of other two groups. Logistic regression analysis showed that the revascularization and the GFR≥60 ml/min were positively correlated with the prognosis of renal function. Conclusions 1-year revascularization indicates a better prognosis of renal function for unilateral ARAS patients with age≤70 years and GFR≥60 ml/min. As for the ARAS patients older than 70 years old， revascularization must be estimated carefully in details.

Objective To observe the change of 24-hour blood pressure and to explore the relation between abnormality of circadian rhythm and renal injury in patients with chronic kidney disease. Methods Circadian blood pressure rhythm was studied by ambulatory 24-hour monitoring in normotensive(n=130) and hypertensive (n=106) patients with chronic kidney disease， and in matched control groups (14 healthy subjects and 43 patients with essential hypertension) without renal disease. Ambulatory blood pressure monitoring(ABPM) was performed with a portable oscillometric recorder(Spacelab 90217). ABP Report Management System Version1.03.03 was used to analyze the 24-hour data. The term “dipper” was described as BP during sleep drops at least 10% below daytime pressure. The term “non-dipper” referred to those subjects in whom the nocturnal decline in BP is reversed， absent， or blunted (ie， less than 10%). Results In normotensive subjects， average night systolic and diastolic BP values were constantly higher in the patients with chronic kidney disease than those in the controls (111.2±10.8 vs 91.6±7.5，68.7±9.5 vs 56.2±4.6，P < 0.05). Average daytime SBP and DBP levels did not differ considerably in CKD patients and essential hypertensivers. The frequency of non-dippers was 70.0% in NCKD group， 81.6% in HCKD group， 37.2% in EH group， 7.14% in NC subjects respectively. The normotensive and hypertensive renal patients had higher heart rate(HR) than the corresponding groups，especially at nighttime， with a significant blunted nocturnal decline as compared to control subjects. The NCKD group and HCKD group revealed a much less pronounced decline in nocturnal mean BP values，with a typical non-dipper pattern.Hypertensives with chronic kidney disease displayed pronounced abnormalities in the 24-hour BP pattern， with markedly blunted nocturnal fall and flattened or reversed day-night circadian rhythm BP values. Conclusions Normotensive patients with chronic kidney disease are exposed to a relative hypertension at nighttime and that renal hypertensive subjects can be underestimated in their hypertensive status if the measurement of BP is confined to daytime. There is a compelling need for studying if treating nocturnal hypertension in CKD can prevent renal disease progression.

Objective To evaluate the restenosis， renal function and blood pressure after renal artery stenting in patients with atherosclerosis renovascular disease. Methods Percutaneous renal artery stent (PTRAS) was performed in 135 patients with single or bilateral renal artery stenosis (≥70%).Clinical data of above patients were studied during follow-up period. Results A total of 147 stents were successfully deployed in 145 lesions of 135 consecutive patients. Seventy percent of the patients were followed-up by renal artery angiography for an average of (7.2±5.6) months. The restenosis rate of the renal artery was 7.4%. Ninety-five percent of patients were followed-up for blood pressure and renal function for an average of (22±6)months. The systolic and diastolic pressure were significantly decreased from 172±23/93±16 mm Hg to 159±20/85±13 mm Hg(P < 0.05). The serum creatitine level and glomerular filtration rate(GFR) did not change significantly during 12 months and 24 months follow-up. Conclusions Implantation of renal artery stent benefits the improvement of blood pressure in the patients with atherosclerosis renal vascular disease with a low renal artery restenosis rate.

Objective To investigate the potential contributing effects of reduced serum fetuin A and coronary artery calcification(CAC) on cardiovascular events in end stage renal disease (ESRD) patients. Methods Thirty-eight ESRD patients on chronic hemodialysis (duration of hemodialysis less than 6 months)were enrolled in this study.Controls consisted of 22 non-ESRD patients with chronic kidney diseases (CKD). Serum fetuin A and related parameters， along with CAC score quantified by Multislice Spiral CT scan， were examined at the initiation of this study. The patients were followed up for 18 months for appraising cardiovascular events defined as cardiac failure， angina pectoris or myocardial infarction. Results During the 18 months follow-up， significant difference in cardiovascular events was documented in patients with ESRD (30 times) and without ESRD (3 times，P=0.001). Eighteen cases of CAC(62.07%)were identified by CT scan in 29 ESRD patients. Stepwise regression analysis in 38 ESRD patients without induction of CAC score indicated that fetuin A(P < 0.01)， LDL-C (P=0.008) and CRP(P=0.014) were independently associated with cardiovascular events. After induction of CAC score， stepwise regression analysis in 29 ESRD patients with CAC showed that fetuin A(P < 0.0005) and CAC score (P=0.006) were associated with cardiovascular events. Serum fetuin A was lower in patients with CAC than that in patients without CAC (P=0.001). Stepwise regression analysis showed that CAC was associated with reduce fetuin A (P < 0.0005) and elevated serum phosphorus (P=0.001). Conclusion Reduced serum fetuin A and coronary artery calcification may contribute to cardiovascular events in ESRD patients receiving hemodialysis.

Objective To investigate the effects of simvastatin on inducible type A scavenger receptor (SR-A) in human glomerular mesangial cells(HMC). Methods HMC were cultured and stimulated with phorbol 12-myristate 13-acetate (PMA).The uptake of fluorescence Dil-labeled acetylated LDL(Dil-Ac-LDL) by HMC was evaluated by confocal microscopy. SR-A mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). Promoter activity of SR-A in HMC was assessed by transient expression assay system. Results Simvastatin (1~10 μmol/L) significantly decreased the uptake of Dil-Ac-LDL by HMC and the SR-A mRNA expression stimulated by PMA. Simvastatin also directly inhibited the mRNA expression in the SR-A cDNA transfected human glomerular measngial cells. Transient expression assay indicated that simvastatin inhibited PMA-induced SR-A promoter activity. The inhibitory effect of simvastatin could be blocked by coincubation with 100 μmol/L of mevalonic acid. Conclusions Simvastatin inhibits the expression of type A scavenger receptor by affecting mevalonate metabolism，which may slow the progression of glomerulosclerosis in chronic renal diseases.

Objective To investigate the effect of 17-β-estradiol on renal interstitial fibrosis after unilateral ureteral obstruction(UUO) in rats. Methods Thirty female Sprague-Dawley rats were randomly divided into four groups:(Ⅰ)control group: rats were treated with sham operation；(Ⅱ)normal estrogen group: rats underwent UUO；(Ⅲ)low estrogen group: rats were ovariectomized(OVX) and underwent UUO； (Ⅳ) high estrogen group: rats underwent UUO and received 17-β-estradiol injection. Rats were sacrificed at day 21 after UUO operation， and the renal tissues were examined by HE， PAS， Masson and PASM stain. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied to determine the protein and mRNA expression of α-SMA and TIMP-1. Results Tubulointerstitial fibrosis was found in group Ⅱ.Compared with group Ⅱ， the lesion was remarkably aggravated in group Ⅲ(P < 0.05) and was attenuated in group Ⅳ(P < 0.05). Compared with control group， the expression of protein and mRNA of α-SMA and TIMP-1 increased significantly in UUO groups(P < 0.01). Compared with group Ⅱ， the expression of protein and mRNA of α-SMA and TIMP-1 in group Ⅲ increased significantly(P < 0.05)，which decreased significantly in group Ⅳ(P < 0.05). Conclusion Estrogen may protect the kidney through the inhibition of expression of α-SMA and TIMP-1， resulting in reduction of extracellular matrix deposition.

Objective To determine the inhibitory effect of a synthetic hexa-peptide GGWSHW (G peptide) derived from thrombospondin-1(TSP1) on TGF-β activation induced by angiotensin Ⅱ (AngⅡ) in cultured human renal tubular epithelial cells. Methods Human proximal tubular epithelial cell line(HK-2) was cultured in vitro， untreated HK-2 cells were acted as normal control group. HK-2 cells were then stimulated by AngⅡ for 1~24 hours (AngⅡ stimulation group)， so that optimal dosage and duration could be chosen. One hour prior to induction， HK-2 cells were pretreated with 10 μmol/L peptide G(G peptide treated group)or losartan (losartan treated group)， the blocker of Ⅰ type receptor of AngⅡ was acted as inhibitory control. The mRNA and protein levels of TSP1， TGF-β1， FN and PAI-1 were measured by RT-PCR and Western blot. Confocal microscopy and flow cytometry were performed to detect the presence of TSP1， TGF-β1 and co-positive expression of two protein， respectively. The concentrations of total and active TGF-β1 as well as FN and PAI-1 in cell culture supernatants were measured by ELISA. Additionally， the expression of Smad2 and p-Smad2 was also examined for the bioactivity of TGF-β1 signaling protein.Results AngⅡ enhanced the expression of TSP1 and TGF-β1 in a temporal-spatial dependent manner. The optimal dosage and duration were 1 μmol/L and 6 hours， for TSP1， and 0.1 μmol/L and 12 hours for TGF-β1 respectively. Comparing with untreated HK-2，the co-expression of TSP1 and TGF-β1 induced by AⅡ showed a increase of 5.4 folds. In addition， the protein level of p-Smad2 was elevated remarkedly， the mRNA level of FN and PAI-1 was up-regulated by 3 and 1.5 folds， and the concentration was increased by 2.0 and 1.9 folds respectively. Peptide G had less effect on the expression of TSP1 and TGF-β1， whereas it significantly reduced the secretion of active TGF-β1， though total level of TGF-β1 remained up-regulated. Furthermore， comparing with losartan treated group， p-Smad2 expression was reduced by 28.9%， the mRNA level of FN and PAI-1 was decreased by 34.5% and 26% respectively， and the protein levels were reduced by 11.0% and 8.9% respectively. Conclusion The inhibitory peptide derived from TSP1 effectively suppresses TGF-β1 activation through a competitive mechanism and also reduces the secretion of FN and PAI-1 associated with fibrosis.

Objective To investigate the mechanism of Rhubarb in treating chronic kidney disease. Methods The animal model of renal disease was induced by unilateral ureteral obstruction (UUO) in CD-1 mice. The mice were divided into three groups: the sham， UUO， and UUO receiving Rhubarb extract treatment (12.5， 25， and 50 mg/kg body weight) daily. The morphological changes and content of total collagen from each group were examined at day 7 following UUO. Meanwhile， the de novo expression of α-smooth muscle actin (α-SMA)， and collagen I in tissues from mice were assessed by Western blotting. Results Administration of Rhubarb extract markedly attenuated renal tissue injury， and decreased total collagen accumulation. The expression of α-SMA was suppressed dramatically in the mice receiving Rhubarb extract treatment (50 mg/kg body weight). In addition， Rhubarb extract inhibited deposition of collagen I significantly. Conclusion Rhubarb extract is a drug for amelioration of renal fibrosis of mice in vivo.

Objective To investigate the effects of TIMP-1 shRNA mediated by pEGFP-1 on the apoptosis of rat mesangial cells(RMC) and the extracellular matrix (ECM) in glomeruli in vitro. Methods Two pEGFP-1/TIMP-1 shRNAs reconstructed plasmids， i.e， pEGFP-1/TIMP-1 shRNA1， pEGFP-1/TIMP-1 shRNA2 which contained enhanced green fluorescent protein(EGFP)gene were constructed. The fluorescent microscopy was used to examine the expression of EGFP. The silencing effects of TIMP-1 on the mRNA and protein levels were examined by reverse transcription PCR (RT-PCR) and Western blot analysis respectively. The protein expression of the ECM components in the supernatant of cell culture was analyzed by ELISA. The apoptotic ratio of RMC was monitored by flow cytometry. Results DNA sequencing confirmed that pEGFP-1/TIMP-1 shRNA was successfully constructed. The expression of EGFP was detected in pEGFP-1/TIMP-1 shRNA transfected cells， but was not trailed in nontransfected cells. Both the mRNA expression and protein secretion of TIMP-1 in shRNA1 transfecting RMC were significantly lower than those in control groups (P < 0.05). However， there was no obvious change in TIMP-1 shRNA2 transfecting group(P > 0.05). In contrast with the control group， the expression of FN， LN and collagen Ⅳ protein significantly decreased in both the shRNA1 and antisense TIMP-1 transfecting groups (P < 0.05). At 24 h， 48 h and 72 h， the ratios of apoptotic cells transfected with pEGFP-1/TIMP-1 shRNA1 were 19.81%±0.66%，45.70%±0.71% and 81.29%±0.55% respectively，which were much higher than those of the negative control group and of the nontransfected group (both P < 0.05). Conclusion The specific TIMP-1 shRNA1 markedly inhibits the expression of TIMP-1 on both the gene and protein levels of RMC， which ultimately results in the promotion of apoptosis of RMC and the degradation of ECM.Objective To investigate the effects of TIMP-1 shRNA mediated by pEGFP-1 on the apoptosis of rat mesangial cells(RMC) and the extracellular matrix (ECM) in glomeruli in vitro. Methods Two pEGFP-1/TIMP-1 shRNAs reconstructed plasmids， i.e， pEGFP-1/TIMP-1 shRNA1， pEGFP-1/TIMP-1 shRNA2 which contained enhanced green fluorescent protein(EGFP)gene were constructed. The fluorescent microscopy was used to examine the expression of EGFP. The silencing effects of TIMP-1 on the mRNA and protein levels were examined by reverse transcription PCR (RT-PCR) and Western blot analysis respectively. The protein expression of the ECM components in the supernatant of cell culture was analyzed by ELISA. The apoptotic ratio of RMC was monitored by flow cytometry. Results DNA sequencing confirmed that pEGFP-1/TIMP-1 shRNA was successfully constructed. The expression of EGFP was detected in pEGFP-1/TIMP-1 shRNA transfected cells， but was not trailed in nontransfected cells. Both the mRNA expression and protein secretion of TIMP-1 in shRNA1 transfecting RMC were significantly lower than those in control groups (P < 0.05). However， there was no obvious change in TIMP-1 shRNA2 transfecting group(P > 0.05). In contrast with the control group， the expression of FN， LN and collagen Ⅳ protein significantly decreased in both the shRNA1 and antisense TIMP-1 transfecting groups (P < 0.05). At 24 h， 48 h and 72 h， the ratios of apoptotic cells transfected with pEGFP-1/TIMP-1 shRNA1 were 19.81%±0.66%，45.70%±0.71% and 81.29%±0.55% respectively，which were much higher than those of the negative control group and of the nontransfected group (both P < 0.05). Conclusion The specific TIMP-1 shRNA1 markedly inhibits the expression of TIMP-1 on both the gene and protein levels of RMC， which ultimately results in the promotion of apoptosis of RMC and the degradation of ECM.