No abstract available.
Humans ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis*

PURPOSE: Efonidipine, which inhibits both T- and L-type calcium channels, has been shown to be effective in reducing proteinuria and preserve renal function. This study was conducted to compare the effects of efonidipine versus amlodipine on the management of hypertension and proteinuria in patients with chronic kidney disease (CKD) receiving ACE inhibitors or ARB. METHODS: This study included 41 CKD patients who were at stages 2-4 and had a urine spot protein/ creatinine ratio of >0.5. Patients were administered amlodipine (5 mg/day) and efonidipine (40 mg/ day) for 3 months in a cross-over design. Blood pressure and spot urine protein/creatinine ratio were compared before and after the cross-over treatment. RESULTS: There were 24 male patients and 17 female patients. The mean age of the patients was 55.9+/-12.9 years. When the patients' medication was changed to eponidifine, we obtained the following results. First, there were no significant changes in blood pressure and serum creatinine. Second, the urine spot protein/creatinine ratio was significantly decreased (before the cross-over, 2.9+/-2.6; after the cross-over, 2.3+/-1.9 g/g; p=0.02). Finally, the reduction rate of proteinuria was significantly higher in patients with CKD at stages 2-3 than in those with CKD at stage 4 after the cross-over (stage 2, - 26.1%; stage 3, -17%; stage 4, +12.8%; p=0.03). CONCLUSION: It is concluded that efonidipine may significantly decrease proteinuria compared with amlodipine in CKD patients receiving ACE inhibitors or ARB. Further double-blind clinical trials with a larger sample size are needed to confirm our results.
Amlodipine ; Angiotensin-Converting Enzyme Inhibitors ; Blood Pressure ; Calcium Channels, L-Type ; Creatinine ; Cross-Over Studies ; Dihydropyridines ; Female ; Humans ; Hypertension ; Male ; Nitrophenols ; Organophosphorus Compounds ; Proteinuria ; Renal Insufficiency, Chronic ; Sample Size

OBJECTIVE: Diverse glomerular disorders leadsing to progressive glomerulosclerosis share the common features of increased mRNA expression for extra- cellular matrix protein and growth factors. The precise role of angiotensin II in contributing to these disturbances is currently unknown. ACE inhibitors have been proved to be beneficial in protecting against glomerular injury in animal models and many of human glomerular diseases. Type IV collagen is a main component of extracellular matrix in the mesangium : its increased accumulation is a common pathologic finding in the glomerulosclerosis. There are some evidences that the beneficial effect of ACE inhibitor does not solely depend on the hemodynamic effect, but may be mediated by other effect. The purpose of this study is to evaluate the effects of high glucose, angiotensin II and angiotensin converting enzyme inhibitor on the expression of PC alpha1(lV) in mesansial cells(MCs). METHODS: Human mesangial cells were cultured with standard method. To investigate the effect of each drug and high glucose condition, MCs were cultured in the normal-glucose medium(100mg/dl) and high-glucose medium(450mg/dl), respectively. An- giotensin II and angiotensin converting enzyme inhibitor(captopril) were added to culture medium at final concentration of 10 M which is the physiologic dose in vivo. MCs were cultured in each condition for 3days, when the maximal effect of high glucose on MCs, and harvested for mesurement of the expression of PC alpha1(IV) mRNA. To quantitate the PC alpha(1V) mRNA levels in each condition, semiquantitatine RT-PCR was done with co-amplification of house keeping gene. RESULTS: PCa1(IV) mRNA expression was significantly increased in high-glucose medium(30mM) compared to normal-glucose medium(5.5mM)(2.28+/-0.34 vs 0.96+/-0.08, p<0.05). Administration of angiotensin ll(10(-6)M) in culture media induced a further increment in the PC a >(IV) mRNA expression to 4.64+/-0.28(p<0.05). Angiotensin II in the normal-glucose medium increased the PC alpha1(lV) mHNA expression as 2.69+/-0.23 control(p<0.05). Addition of angiotensin converting enzyme inhibitor(Capopril, 10(-6)M) in high- glucose culture medium significantly suppressed the PC alpha1(IV) mRNA expression as 0.690.11(p<0.05). CONCLUSION: High glucose concentration in culture medium significantly increases the mRNA expression of procollagen alphal(IV) than normal glucose concentration. Angiotensin II increases the collagen mRNA expression directly and this effect was significantly prevented by ACE inhibitor. This result suggests that hyperglycemia in diabetic millieu can directly increase collagen production, and ACE inhibitor may inhibit progressive glomerulosclerosis by decreasing collagen production as well as reducing intraglomerular pressure.
Angiotensin II ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins* ; Collagen ; Collagen Type IV ; Culture Media ; Extracellular Matrix ; Glucose* ; Hemodynamics ; Humans* ; Hyperglycemia ; Intercellular Signaling Peptides and Proteins ; Mesangial Cells* ; Models, Animal ; Peptidyl-Dipeptidase A ; Procollagen ; RNA, Messenger*

OBJECTIVE: Diabetic nephropathy is an important cause of end stage renal disease in Korea and associated with major morbidity and mortality. The precise pathogenic mechanism of this disease is still controversial, but it has been considered that multiple factors are contribute to the development and progression of diabetic nephropathy. One of these factors, renin-angiotensin system has been proven to be a major mediator of this disease via activation of angiotensin II, which has multiple functions such as induction of production of extracellular matrix protein and various intraglomerular cells, tubulointerstital component and increment of intraglomerular pressure. Transforming growth factor(TGFbeta) is a multifunctional cytokine with major profibrotic character, which stimulates the production of extracellular matrx(ECM) protein, inhibit the degradation of ECM and induce the interaction of mesangial cells with ECM via integrin receptors. This study was done to evaluate the role of angiotensin II and angiotensin converting enzyme inhibitor in expression of TGFbeta mRNA which is a main mediator in the pathogenesis of diabetic nephropathy. METHODS: Human mesangial cells(MCs) were cultured by standard culture techniqne. For this study, cells in the 5th to 7th passage were used. To make a different glucose concentration in culture medium, normal(100mg/dl) or high glucose(450mg/dl) concentrations of D-glucose were added, and cultured in 17% heat inactivated fetal bovine serum. Angiotensin II and ACE inhibitor(captopril) were administered to the culture medium at final concentration of 10-6M. After 72 hours, MCs were harvested to measure the expression of TGFbeta mRNA. To measure the mRNA expression of TGFbeta in each condition, semi quantitative PCR was done and all results were corrected by beta-actin gene. RESULTS: mRNA expression of TGFbeta was significantly increased in the high glucose medium(30 mM) compared to normal glucose medium(5.5mM) (3.82+/-0.465 vs 2.27+/-0.13, p<0.05). Administration of angiotensinII(10-6M) in high glucose medium induced a further increase in the TGFbeta expression to 4.29+/-0.476(p<0.05). AngiotensinII(10-6M) in normal glucose medium also showed a significant increase in TGFbeta expression as 3.40+/-1.88(p<0.05). Administration of ACE inhibitor(Captopril, 10-6M) in high glucose medium prevented the increse of TGFbeta expression(1.20+/-0.18 vs 3.82+/-0.465, p<0.05). CONCLUSION: From these findings, it suggest that angiotensinII is an important mediator in the pathogenesis of diabetic nephropathy. ACE inhibitor may have a role in the progress of this disease via direct suppression of TGFbeta system as well as beneficial intraglomerular hemodynamic effect.
Actins ; Angiotensin II* ; Angiotensins* ; Diabetic Nephropathies ; Extracellular Matrix ; Glucose* ; Hemodynamics ; Hot Temperature ; Humans* ; Kidney Failure, Chronic ; Korea ; Mesangial Cells* ; Mortality ; Peptidyl-Dipeptidase A ; Polymerase Chain Reaction ; Renin-Angiotensin System ; RNA, Messenger* ; Transforming Growth Factor beta*

BACKGROUND: Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. RESULTS: The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=0.809, p=0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
Cells, Cultured ; Female ; Glomerular Mesangium/*cytology/metabolism ; Glomerulonephritis, IGA/metabolism/pathology ; Humans ; Immunoglobulin A/*pharmacology ; Male ; Proteins/*metabolism ; RNA, Messenger/*metabolism ; Research Support, Non-U.S. Gov't

A multicenter prospective study was done in four-university hospital to evaluate the efficacy and safety of cyclosporin A(CyA, Cipol-N(R)) in 64 patients with adult nephrotic syndrome mean age 34.8 years, male:female 2.4:1, duration of disease 38.0+/-40.9months, 31 patients with MCD, 33 patients with Non-MCD (8 FSGS, 14 MGN, 7 MPGN, 2 lupus nephritis, 1 HBsAg associated GN)]. The prior steroid responses of these patients were 17 steroid dependent, 9 frequent relapser, 4 steroid resistant and 1 other in MCD patients, and 5 steroid dependent, 5 frequent relapser, 22 steroid resistant and 1 other in Non-MCD patients. After a 2-week steroid (predni-solon 10mg/day or deflazacort 12mg/day) run-in period, CyA 5mg/kg/day and prednisolone 10mg/day (or deflazacort 12mg/day) were administered for up to 16 weeks. Of the 64 patients enrolled, ll patients were dropped out prematurely due to adverse events or protocol violation. Of the 53 patients who completed the study, 27 had MCD and 26 had Non- MCD. High response (CR and PR) rate of 68% (36/53) were obtained with CyA treatment in all patients. Although the response rate in MCD was significantly higher than that in Non-MCD (89 vs. 46%, p<0.05) and response rates were significantly different according to the previous steroid responses by univariate analysis, only previous steroid responses affected the response to CyA significantly by Logistic multiple regression analysis (p=0.03, RR 7.08); responses were 84% (27/32) in steroid dependent and frequent relapser patients, and 37% (7/19) in steroid resistant patients. 24-hr proteinuria significantly decreased after 2 weeks and serum albumin and cholesteroi increased significantly after 4 weeks of treatment compared to baseline level. The serum creatinine level was not changed during the study. No serious and unexpected side event was observed. In conclusion, cyclosporine therapy is a safe and effective mode of treatment in patients with ne-phrotic syndrome, especially in those who need prolonged administration of steroids with resulting in unavoidable steroid complications such as frequent relapser and steroid dependent type. The patients with steroid resistant type and contraidications of steroid administration such as DM, aseptic bone neerosis etc. can also be candidates for this treatment.
Adult* ; Creatinine ; Cyclosporine* ; Glomerulonephritis, Membranoproliferative ; Hepatitis B Surface Antigens ; Humans ; Lupus Nephritis ; Nephrotic Syndrome ; Prednisolone ; Prospective Studies ; Proteinuria ; Serum Albumin ; Steroids