Hypertension control is the most important and effective treatment for chronic kidney diseases.Compared with hypertension patients without kidney diseases,it requires a stricter blood pressure control in those with kidney diseases.The treatment principles are:(i)To lower the blood pressure is the top priority;and(ii)the impacts of various antihypertensive drugs on individual patients.The antihypertensive drugs should be chosen taking into consideration of the following factors:the extent of hypertension,whether the hypertension occurs abruptly or permanently,the heart and renal functions and any significant metabolic disorders.Among the existing drugs,diuretic is usually hampered by renal dysfunction;ACEI/ARB seems to be more effective on patients with proteinuria,but it should be used with caution in patients with severe renal insufficiency;CCB is effective and can quickly lower blood pressure,therefore it is an essential drug for hypertension treatment;?-blocker is not considered as a main drug for hypertension with kidney diseases.Combination use of anti-hypertensive drug is common to many CKD with hypertension,among them ACEI/ARB+diuretic,ACEI/ARG+CCB are the most common combinations.ACEI+ARB exhibit a better proteinuria reduction effect;however it is not indicated in patients with severe cardiovascular lesion.Hypertension treatment should take into consideration of individual differences and should be adjusted according to individual responses.Salt intake control also plays an important role in the successful treatment of hypertension with kidney diseases.

AIM To explore the effect of ACE inhibitor on early kidney hypertrophy and its mechanism in diabetic rats. METHODS Rats were randomly divided into three groups: uninephrectomized rats, streptozotocin induced diabetic rats and diabetic rats treated with benazepril (an ACE inhibitor, 10 mg?kg -1 ?d -1 , ig). Activity of ACE was determined by the fluorimetric assay. Expression of TGF? 1 mRNA and TGF? 1 and p21 CIP1 protein was measured by Northern blot analysis and Western blot analysis, respectively. RESULTS After 1 week, the diabetic rats developed a body weight loss, kidney weight/body weight increased and renal cortex ACE activity elevated despite a decrease in plasma ACE activity. Northern blot analysis showed that renal cortex TGF? 1 mRNA expression in the diabetic rats was enhanced by 1.3 times, compared with uninephrectomized rats. Western blot analysis showed that TGF? 1 and p21 CIP1 protein expression were also increased. Administration of benazepril for one week significantly suppressed kidney hypertrophy. ACE activity in the plasma, renal cortex and medulla was reduced by 89%,70% and 70 5%, respectively. Expression of TGF? 1 mRNA as well as expression of TGF? 1 and p21 CIP1 protein was reduced by 47 7%, 49 5% and 60 0%, respectively. CONCLUSION Our results suggest that the suppression of ACE inhibitor on diabetic kidney hypertrophy might partially be associated with a decrease in the expression of TGF? 1 and p21 CIP1 in diabetic rats renal cortex. However, its exact mechanism remains to be further explored.

AIM: To study effect of benazepril (an ACE inhibitor) on expression of insulin receptor (IR) and its substrate-1(IRS-1) protein in renal tissue cell membrane in diabetic rats. METHODS: The rats were randomly divided into following groups: control (n=6), streptozotocin induced diabetic (n=7) and diabetic treated with benazepril (n=7). Body weight, kidney weight and kidney weight/body weight were observed after 4 weeks of treatment. ACE activities in plasma, renal tissue were measured by the fluorimetric assay. The expressions of IR and IRS-1 protein were determined by Western blot analysis in renal tissue cell membrane. RESULTS: After 4 weeks of treatment, benazepril significantly ameliorated kidney hypertrophy in diabetic rats. ACE activities in plasma, renal tissue were redunced by approximately 92.00% and 88.77%, respectively. Western blot analysis showed that the expressions of IR and IRS-1 protein were increased by 2.1 and 1.5 folds in renal tissue cell membrane in diabetic rats. However, benazepril reduced expression of IR and IRS-1 protein by 45.74% and 47.66%, respectively. CONCLUSIONS: Increased expression of IR and IRS-1 protein might be related to abnormally active glucose metabolism in diabetic rat kidney. Down-regulation of expression of IR and IRS-1 protein might be one of important machnisms of Benazepril nephroprotection on diabetic rats.

Objective To probe the changes of RAGEmRNA expression in renal tissue of.streptozotocin (STZ)-induced diabetic rats. Methods Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used in control rats and diabetic rats for 12 weeks. Results After 4 weeks of diabetes inducement, RACEmRNA level showed a continuous increase both in diabetic renal cortex and medulla. However, this enhancement could not be observed in 2 weeks of diabetes. In addition, after 8 weeks diabetic rats had significantly higher glycated Hb(GHb). Conclusion Gene expression of RAGE in renal tissue of diabetic rats is altered and the excessive gene expression of RAGE may enhance the AGEs-RAGE interactions which would contribute to the development of diabetic nephropathy. Furthermore, this change occurs as a result of hyperglycemia-induced AGEs formation.

Objective To investigate the expression of transforming growth factor ?_1(TGF?_1)in renal cortex from uninephrectomized diabetic rats. Methods Wistar rats were divided into uninephrectomized rats(group A), streptozotocin diabetic rat(group B). Blood glucose, serum insulin level and body weight, kidney weight, kidney weight/body weight as well as renal tissue protein contents were observed after 1, 4 weeks of streptozotocin injection. The expression of TGF?_1, precollagen 1?(Ⅳ) and fibronectin mRNA were measured by Northern blot analysis, and TGF?_1 protein by Western blot analysis in kidney cortex. In addition, ACE activities were determined by fluorimetric assay in plasma, kidney cortex and medulla. Results Group B demonstrated significantly elevated blood glucose and decreased serum insulin level. Kidney weight、kidney weight/body weight and renal tissue protein contents progressively increased despite total body weight loss. There was significant(P

Purpose To evaluate apoptosis in renal tissue of diffuse proliferative lupus nephritis and therelationship between the existence of apoptosis cells in renal tissue and histopathological or clinical changes.Methods Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25patients with type Ⅳ LN, 12 patients with IgAN, 4 patients with MsPGN, and 3 patients with APSGN. Normalrenal tissue obtained at nephrectorny for hypemephroma in 4 adults was used as control. In addition, proliferatingcells were identified by proliferating cell nuclear antigen(PCNA) in these patients. Results Compared to otherproliferative glomerulonephritis and control,the patients with lupus nephritis had less apoptosis cells, higher ratio ofPCNA+ cells/TdT+ cells/(P/T) in renal tissues;Ratio of P/T in glomeruli and tubulointerstitium correlated withthe chronicity index, r=0. 498 3(P = 0. 013 2), r = 0. 839 9(P＜ 0.001 ), r = 0. 661 4(P = 0. 003 3),respectively. Ratio of P/T in glomerulus and tubule had positive correlation with 24 hour urinary protein, r =0.855 4(P＜0.001),r=0.713 4(P=0. 001); negative correlation with Ccr, r = - 0. 488 0(P =0. 013 3)and r = - 0. 722 9(P = 0. 001), which in tubules positively correlated with Scr, r = 0. 410 7 (P = 0.041 4 ).Conclusions Apoptosis is insufficient in proliferative lupus nephritis. Intense proliferation without followingincrease in apoptosis may be related to chronic progressive renal histopatholcgical changes.

Uninephrectomy was performed in a ll rats of this study, and diabetic model was induced in partial rats by streptozo tocin. Then these rats were divided into uninephrectomy group, diabetes group an d benazepril-treated diabetes group. After 4 weeks, renal tubulo-interstitial morphological change was observed and type Ⅳ collagen, fibronectin and transfor ming growth factor ? 1 (TGF-? 1) proteins as well as TGF-? 1 mRNA were d etermined. The results suggested that benazepril played a protective role in ren al tubulo-interstitial injury, which was associated partially with down-regula ted overexpression of TGF-? 1.

Objective To investigate the expression and translocation of protein kinase C (PKC) ?Ⅱ isoform in renal tissue of diabetic rats and the effects of blocking renin-angiotensin system (RAS) on them. Methods Diabetic rats induced with streptozotocin were randomized to 4 groups. (1) Diabetic control without treatment. (2) Treatment with irbesartan (40 mg?kg -1 ?d -1 ). (3)Treatment with fosinopril (40 mg?kg -1 ?d -1 ) and (4) Treatment with a combination of irbesartan and fosinopril (20 mg?kg -1 ?d -1 each). Six normoglycemic rats served as normal control. After 4 weeks, blood glucose and insulin were measured and expression and translocation of PKC?Ⅱ in renal cortex and medulla were assessed by immunohistochemistry and Western blot. Results The expressions of total and membrane fraction in renal cortex of diabetic control rats weredecreasedto66.0%and50.0% of the values of normal control rats respectively (both P

Objective To understand the situation of oxidative stress among diabetic nephropathy (DN) patients and observe the antioxidative effect of losartan at increasing dose in DN patients. Methods Thirty type 2 DN patients who neither smoked and nor took antioxidants were selected. The study began with an initial 4-6 weeks screening-treatment. Eligible patients then received losartan 50 mg/d daily for 8 weeks followed by losartan 100 mg/day daily for an additional 8 weeks. Blood glucose and blood pressure were closely monitored over the whole study period. All patients were followed up every other weeks, their 24-hour urine samples,fresh urine and venous blood sample were collected to measure urinary protein and creatinine excretion, urinary 8-OHdG, SOD, TAOC and MDA excretion , serum SOD, TAOC , MDA and other blood biochemistry parameters. Urinary 8-OHdG was determined by capillary electrophoresis and liquid phase chromatography. Results The total 24 hours urinary 8-OHdG excretion and the serum MDA concentration were higher than the normal values. The serum and urine SOD concentrations were lower than the normal values. There was an improvement in urinary 8-OHdG,serum and urine SOD, serum and urine MDA levels with losartan therapy. Compared with losartan 50 mg/d, the antioxidative effect of losartan 100 mg/d was more noticeable. Obvious decrease in 24-hour proteinuria on exposure to losartan was found, without severe adverse effect. Conclusions Oxidative stress damage is active in DN patients. Losartan has antioxidative effect on DN patients. Compared with losartan 50 mg/d, the antioxidative effect of losartan 100 mg/d is more marked, without increasing side effect. Losartan's antioxidative effect may be involved in its beneficial mechanisms on DN.

Objective To study the inhibitive effect and mechanism of PPAR?1 on the extracellular matrix (ECM) accumulation of mesangial cells induced by Ang Ⅱ .Methods The plasmid of PPAR?1/WT (wild type) was transfected into mesangial cells. After 48 hours of Ang Ⅱ stimulation, the gene expression of TGF-?1, PAI-1, c-fos and c-jun was examined by RT-PCR. Protein levels of p-ERK, I-?B and nucleus/cytosol ratio of NF-?B were estimated by Westen-blot. The concentrations of FN and TGF-?1 were estimated by ELISA. The activity of PPAR?1 was examined by specific PPRE binding activity. Plasmid expressing non-functional dominant negative type of mPPAR?1, pIRES2-EGFP-mPPAR?1/DN (DN), and blank plasmid, pIRES2-EGFP (Blank) were used as controls. Effects of 6 ?mol/L PPAR? agonist pioglitazone (Pio) were also studied. Results The expression of TGF-?1 and PAI-1 mRNA in mesangial cells induced by Ang Ⅱ was inhibited by PPAR?1(P