Abstract 409: Effects of Angiotensin II Receptor Blocker (ARB) and PPAR-gamma Agonist on Vascular Failure in Patients with Hypertension, Diabetic Mellitus and Chronic Kidney Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideki Watanabe ◽  
Kunio Nakagawa ◽  
Masaaki Kakihana
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Sensitivity ◽  
Ppar Gamma ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Ppar Γ ◽  
Ckd Stage ◽  
Measured Flow

Background: Hypertension (HT), diabetes mellitus (DM), and chronic kidney disease (CKD) are known to be associated with “vascular failure”, which is defined as the integration of endothelial dysfunction and metabolic abnormalities of the vessel wall including inflammation, oxidative stress. We evaluated effects of ARB, calcium channel blocker (CCB), and PPAR-γ agonist on vascular failure in patients with HT, DM and CKD. Methods: Forty eight patients with untreated HT, type 2 DM (HbA1c 6.0 – 6.5%), and CKD (stage 3 or 4) were randomized to receive telmisartan ( Tel. group , n=12), telmisartan and pioglitazone ( Tel. and Pio. group , n=12), amlodipine ( Aml. group , n=12), or amlodipine and pioglitazone ( Aml. and Pio. group , n=12). We measured flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery, and pulse wave velocity (PWV). We also measured high sensitivity C-reactive peptide (hsCRP) and TBARS levels as indexes of inflammation and oxidative stress. Measurements were performed at baseline, and then at every 6 months after the treatments. Results: Blood pressure was significantly decreased in these groups, and there was no difference among four groups at baseline and during the study. FMD was significantly increased, and PWV, hsCRP, and TBARS were significantly decreased in four groups. However, these improvements were much better in the Tel. and Pio. group than the other groups. NID did not change during the study. Conclusion: Combination therapy with ARB and PPAR-γ agonist was much better in the improvement of vascular failure in patients with HT, DM and CKD as compared with the therapy with ARB alone, CCB alone, or CCB and PPAR-γ agonist.

scholarly journals Nephroprotective strategy in the treatment of hypertension as a modern general medical problem

2018 ◽  
pp. 107-118 ◽  
Author(s):  
V. I. Podzolkov ◽  
A. E. Bragina ◽  
T. I. Ishina ◽  
L. V. Bragina ◽  
L. V. Vasilyeva
Keyword(s):  
Chronic Kidney Disease ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Medical Problem ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
High Prevalence ◽  
Advanced Stages ◽  
Receptor Blockers

The current population is characterized by a high prevalence of risk factors for the development of chronic kidney disease: hypertension, diabetes, obesity, metabolic syndrome, physical inactivity, smoking. The development of severe complications and a close connection with potentially fatal cardiovascular disorders make this disease a socially and economically significant problem. Treatment of chronic kidney disease in advanced stages belong to nephrologist duties. However, the success of preventive interventions depends on the time of their onset, which makes it relevant to identify the disease. The use of nephroprotective approaches by physicians of different specialties (general practitioners, cardiologists, gerontologists, nephrologists, endocrinologists) can significantly improve the prognosis of both those at risk of developing renal dysfunction and the existing disease. The review presents data on the clinical and laboratory efficacy of angiotensin-renin blocker use, as well as the combination of angiotensin II receptor blockers with calcium antagonists. Using the combination of the angiotensin II receptor blocker irbesartan and amlodipine as an example, we demonstrated the possibilities of nephroprotective therapy in patients with renal dysfunction.

scholarly journals Thrombomodulin as a New Marker of Endothelial Dysfunction in Chronic Kidney Disease in Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Dorota Drożdż ◽  
Monika Łątka ◽  
Tomasz Drożdż ◽  
Krystyna Sztefko ◽  
Przemko Kwinta
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Cystatin C ◽  
Oxidized Ldl ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Oxidative Stress Biomarkers ◽  
Ckd Stage

Endothelial dysfunction (ED) and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL), protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA), von Willebrand factor, brain natriuretic peptide (BNP), lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP) measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1) years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine (R=0.666; p<0.001), cystatin C (R=0.738; p<0.001), BNP (R=0.406; p=0.001), ADMA (R=0.353; p=0.01), oxLDL (R=0.340; p=0.009), 24-hour systolic (R=0.345; p=0.011) and mean (R=0.315; p<0.05) BP values, and left ventricular mass index (LVMI, R=0.293; p=0.024) and negatively with estimated glomerular filtration rate (R=−0.716; p<0.001). In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.

scholarly journals ACTI ON OF N- ACETYLCYSTEI NE ON ASYMMETRI C DIMETHYLARGININE AND ALBUMINURIA IN STAGE 1-4 NONDIABETIC CHRONIC KIDNEY DISEASE PATIENTS

2010 ◽  
Vol 1 (3) ◽  
pp. 146
Author(s):  
MOCHAMMAD THAHA ◽  
Widodo Widodo ◽  
Moh. Yogiantoro ◽  
WENNY PUTRI NILAMSARI ◽  
MOCHAMAD YUSUF ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Treatment Group ◽  
Kidney Disease ◽  
Day Treatment ◽  
Oral Treatment ◽  
Control Group ◽  
Adma Level ◽  
Ckd Stage ◽  
Stage 1

Background: Uremic patients are in a pro-oxidant state and show an increased level of asymmetric dimethylarginine (ADMA), which is due to increased PRMT1 activity and reduced dimethylarginine dimethylaminohydrolase (DDAH) as degradation enzymes. Reactive oxidant species may play an important role in increasing the action of PRMT1 and in inhibiting the action of DDAH. Albuminuria and ADMA are closely correlated with progression of cardiovascular disease in chronic kidney disease (CKD) patients as well as indicators for decreasing renal function. Although ACEIs and/or ARBs reduced albuminuria in CKD patients, the results are still conflicting. Several factors in these patients may play important roles in the mechanism of albuminuria such as oxidative stress. The antioxidant N-acetylcysteine may prove to have beneficial therapeutic effect, because it can reduce oxidative stress as shown by evidence in humans, and subsequently increase ADMA. The objective of the present study is to explore the contribution of the antioxidant N-acetylcysteine (NAC) to the decrease of ADMA and albuminuria in non-diabetic CKD patients. Material and Methods: Patients with non-DM CKD stage 1–4 with albuminuria were randomized to receive ACEI and/or ARB alone (control group) or with antioxidant NAC 600 mg orally twice a day (treatment group). Observations were performed for 3 months to measure ADMA and albuminuria before and after-treatment. 80 patients in total 40 in the control group and 40 in the treatment group were used. Results: After oral treatment with NAC, the plasma level of ADMA in the treatment group increased from 0.604 µmol/l to 0.689 µmol/l, whereas ADMA level in the control group exhibited a higher increase from 0.561 µmol/l to 0.743 µmol/l. The increases in these groups were significantly different (p < 0.02). Moreover, the level of albuminuria was reduced from 148.12 µg/mg • cr to 132.7 µg/mg • cr in the treatment group, and from 75.25 µg/mg • cr to 71.85 µg/mg • cr in the control group. The difference was significant (p < 0.001). Conclusion: The anti-oxidant N-acetylcysteine can be used as adjuvant therapy to inhibit the progression of CKD in patients by decreasing the ADMA level and albuminuria.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial

2020 ◽  
Author(s):  
Sydney C W Tang ◽  
Kam Wa Chan ◽  
Dennis K M Ip ◽  
Desmond Y H Yap ◽  
Maggie K M Ma ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Rate Of Change ◽  
Control Group ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Open Label ◽  
Baseline Serum

Abstract Background The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. Methods In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Results Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Conclusion Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

scholarly journals Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients

2020 ◽  
Author(s):  
Andressa Keiko Matsumoto ◽  
Michael Maes ◽  
Ana Paula Michelin ◽  
Abel Esteves Soares ◽  
Laura de Oliveira Semeão ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vitamin D Deficiency ◽  
High Sensitivity ◽  
Cross Sectional Study ◽  
Dialysis Patients ◽  
Cross Sectional ◽  
Vitamin D Levels

Abstract Introduction: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. Methods: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. Results: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. Conclusions: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

scholarly journals Effect of angiotensin II receptor blocker therapy on markers of fibrosis and immune inflammation in hypertensive patients with chronic kidney disease after ischemic stroke

2021 ◽  
Vol 20 (7) ◽  
pp. 3078
Author(s):  
O. A. Osipova ◽  
E. V. Gosteva ◽  
O. N. Belousova ◽  
T. P. Golivets ◽  
J. Yu. Chefranova ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Blocker Therapy ◽  
Hypertensive Patients ◽  
Tnf Α ◽  
Immune Inflammation

Aim. To compare the effect of angiotensin II receptor blocker therapy (azilsartan, telmisartan) on fibrosis and immune inflammation markers in hypertensive patients with chronic kidney disease (CKD) after ischemic stroke (IS).Material and methods. The study included 76 hypertensive patients aged 60-74 years (mean age, 66±5 years) with CKD after IS. Patients were randomly divided into following pharmacotherapy groups: 38 patients — telmisartan group; 36 patients — azilsartan group. The control group consisted of 20 hypertensive people (mean age, 63±2 years) without a history of CKD and IS. The levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by enzyme-linked immunosorbent assay (ELISA Kit, USA). The levels of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), interferon γ (INF-γ), monocytic chemoattractant protein 1 (MCP-1) were assessed using Vector-Best kit (Russia).Results. Six-month azilsartan therapy led to a decrease in the levels of MMP-9 by 19,9% (p<0,01), TIMP-1 by 7,5% (p<0,05), IL-1β by 7,8%, TNF-α by 13,5%, INF-γ by 7,1%, MCP-1 by 13% (p<0,05). Telmisartan therapy was associated with a decrease in the levels of MMP-9 by 39,1% (p<0,01), TIMP-1 by 16,4%, IL-1β by 10,1% (p<0,05), TNF-α by 20,8% (p<0,01), INF-γ by 14,6% (p<0,05), MCP-1 by 21,3% (p<0,01). Intergroup comparison revealed more pronounced changes in the levels of MMP-9 by 19,2% (p<0,01), TIMP-1 by 7,2% (p<0,05), TNF-α by 7,3% (p<0,05), INF-γ by 7,5% (p<0,05), and MCP-1 by 8,3% (p<0,05) when using telmisartan compared to azilsartan. When using telmisartan, the increase in glomerular filtration rate (GFR) was 14,2% (p<0,05) higher compared to azilsartan.Conclusion. Six-month telmisartan therapy in hypertensive patients with CKD after stroke was accompanied by a more pronounced decrease in markers of myocardial fibrosis (MMP-9, TIMP-1) and immune inflammation (TNF-α, INF-γ, MCP-1) compared with azilsartan, as well as with more pronounced improvement in renal function.

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