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Publication Record


Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis.
Kaseda R, Tsuchida Y, Gamboa JL, Zhong J, Zhang L, Yang H, Dikalova A, Bian A, Davies S, Fogo AF, Linton MF, Brown NJ, Ikizler TA, Kon V
(2018) Nutr Metab Cardiovasc Dis 28: 582-591
MeSH Terms: Adult, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Biomarkers, Cholesterol, HDL, Double-Blind Method, Female, Humans, Inflammation Mediators, Kidney Failure, Chronic, Male, Middle Aged, Oxidative Stress, Ramipril, Renal Dialysis, Tennessee, Time Factors, Treatment Outcome, Valsartan
Show Abstract · Added August 3, 2018
BACKGROUND AND AIMS - Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD.
METHODS AND RESULTS - HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA.
CONCLUSION - Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.
Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
1 Communities
3 Members
0 Resources
19 MeSH Terms
Acute kidney injury is a risk factor for subsequent proteinuria.
Parr SK, Matheny ME, Abdel-Kader K, Greevy RA, Bian A, Fly J, Chen G, Speroff T, Hung AM, Ikizler TA, Siew ED
(2018) Kidney Int 93: 460-469
MeSH Terms: Acute Kidney Injury, Aged, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Blood Pressure, Comorbidity, Databases, Factual, Diabetes Mellitus, Diabetic Nephropathies, Disease Progression, Female, Glomerular Filtration Rate, Hospitalization, Hospitals, Veterans, Humans, Hypertension, Kidney, Male, Middle Aged, Prevalence, Prognosis, Proteinuria, Renal Insufficiency, Chronic, Retrospective Studies, Risk Factors, Severity of Illness Index, Time Factors, United States
Show Abstract · Added November 29, 2018
Acute kidney injury (AKI) is associated with subsequent chronic kidney disease (CKD), but the mechanism is unclear. To clarify this, we examined the association of AKI and new-onset or worsening proteinuria during the 12 months following hospitalization in a national retrospective cohort of United States Veterans hospitalized between 2004-2012. Patients with and without AKI were matched using baseline demographics, comorbidities, proteinuria, estimated glomerular filtration rate, blood pressure, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEI/ARB) use, and inpatient exposures linked to AKI. The distribution of proteinuria over one year post-discharge in the matched cohort was compared using inverse probability sampling weights. Subgroup analyses were based on diabetes, pre-admission ACEI/ARB use, and AKI severity. Among the 90,614 matched AKI and non-AKI pairs, the median estimated glomerular filtration rate was 62 mL/min/1.73m. The prevalence of diabetes and hypertension were 48% and 78%, respectively. The odds of having one plus or greater dipstick proteinuria was significantly higher during each month of follow-up in patients with AKI than in patients without AKI (odds ratio range 1.20-1.39). Odds were higher in patients with Stage II or III AKI (odds ratios 1.32-1.81) than in Stage I AKI (odds ratios 1.18-1.32), using non-AKI as the reference group. Results were consistent regardless of diabetes status or baseline ACEI/ARB use. Thus, AKI is a risk factor for incident or worsening proteinuria, suggesting a possible mechanism linking AKI and future CKD. The type of proteinuria, physiology, and clinical significance warrant further study as a potentially modifiable risk factor in the pathway from AKI to CKD.
Published by Elsevier Inc.
0 Communities
1 Members
0 Resources
29 MeSH Terms
Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH) Trial.
Le CN, Hulgan T, Tseng CH, Milne GL, Lake JE
(2017) PLoS One 12: e0170515
MeSH Terms: Adipose Tissue, Adult, Angiotensin II Type 1 Receptor Blockers, Anthropometry, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Benzimidazoles, Benzoates, Body Fat Distribution, Eicosanoids, Female, HIV Infections, Humans, Inflammation, Lipodystrophy, Male, Middle Aged, Oxidative Stress, Pilot Projects, Prospective Studies, Sex Factors, Telmisartan, Waist-Hip Ratio
Show Abstract · Added December 11, 2019
OBJECTIVES - Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial.
METHODS - Thirty-five HIV+ adults (15 women; 20 men) completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB-M) were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman's rho assessed correlations between clinical factors and eicosanoid levels.
RESULTS - Median PGE-M increased on telmisartan (p<0.01), with greater changes in men (+4.1 [p = 0.03] vs. +1.0 ng/mg cr in women; between-group p = 0.25) and participants losing >5% VAT (+3.7 ng/mg cr, p<0.01) and gaining >5% SAT (+1.7 ng/mg cr, p = 0.04). Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08) and did not change on telmisartan.
CONCLUSIONS - Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.
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MeSH Terms
Effects of losartan treatment on the physicochemical properties of diabetic rat bone.
Donmez BO, Unal M, Ozdemir S, Ozturk N, Oguz N, Akkus O
(2017) J Bone Miner Metab 35: 161-170
MeSH Terms: Absorptiometry, Photon, Angiotensin II Type 1 Receptor Blockers, Animals, Biomechanical Phenomena, Bone Density, Bone and Bones, Diabetes Mellitus, Experimental, Female, Losartan, Rats, Rats, Wistar, Renin-Angiotensin System, Spectroscopy, Fourier Transform Infrared
Show Abstract · Added March 3, 2017
Inhibitors of the renin-angiotensin system used to treat several diseases have also been shown to be effective on bone tissue, suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce fracture risk. The present study investigated the effects of losartan on the physicochemical and biomechanical properties of diabetic rat bone. Losartan (5 mg/kg/day) was administered via oral gavage for 12 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Whole femurs were tested under tension to evaluate the biomechanical properties of bone. The physicochemical properties of bone were analyzed by Fourier transform infrared spectroscopy. Although losartan did not recover decreases in the BMD of diabetic bone, it recovered the physicochemical (mineral and collagen matrix) properties of diabetic rat bone. Furthermore, losartan also recovered ultimate tensile strength of diabetic rat femurs. Losartan, an angiotensin II type 1 receptor blocker, has a therapeutic effect on the physicochemical properties of diabetic bone resulting in improvement of bone strength at the material level. Therefore, specific inhibition of this pathway at the receptor level shows potential as a therapeutic target for diabetic patients suffering from bone diseases such as osteopenia.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study.
Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA
(2015) BMC Nephrol 16: 167
MeSH Terms: Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Arginine, Bradykinin, Cell Line, Cross-Over Studies, Double-Blind Method, Endothelium, Vascular, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Ramipril, Renal Dialysis, Valsartan
Show Abstract · Added November 5, 2015
BACKGROUND - Endothelial dysfunction occurs in patients with end-stage renal disease (ESRD) and is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) contributes to endothelial dysfunction in ESRD. In the general population, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease ADMA levels, but no study has compared the effect of these drugs in patients with ESRD on maintenance hemodialysis (MHD).
METHODS - We evaluated the effect of 1-week treatment with ramipril (5 mg/d), valsartan (160 mg/d), and placebo on ADMA levels in 15 patients on MHD in a double-blind, placebo-controlled, three x three cross-over study.
RESULTS - We found that ADMA levels were increased at baseline and throughout the dialysis session during ramipril treatment (p < 0.001 compared to both, placebo and valsartan). Ramipril did not increase ADMA levels in a study of patients without ESRD, suggesting that factors related to ESRD or hemodialysis contribute to the ACE inhibitor-induced increase in ADMA. We have previously shown that ACE inhibition increases bradykinin (BK) levels during hemodialysis. We therefore evaluated the effect of bradykinin on ADMA production in A549 cells; a cell line that expresses BK receptors. Incubation with BK increased intracellular ADMA concentration through BK B2-receptor stimulation.
CONCLUSION - These data indicate that short-term ACE inhibition increases ADMA in patients on MHD whereas ARBs do not. In vitro studies further suggest that this may occur through BK-mediated increase in ADMA production during ACE inhibition.
TRIAL REGISTRATION - Clinicaltrials.gov NCT00732069 August 6 2008 and NCT00607672 February 4 2008.
0 Communities
3 Members
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16 MeSH Terms
Visit-to-visit variability in blood pressure and kidney and cardiovascular outcomes in patients with type 2 diabetes and nephropathy: a post hoc analysis from the RENAAL study and the Irbesartan Diabetic Nephropathy Trial.
McMullan CJ, Lambers Heerspink HJ, Parving HH, Dwyer JP, Forman JP, de Zeeuw D
(2014) Am J Kidney Dis 64: 714-22
MeSH Terms: Aged, Angiotensin II Type 1 Receptor Blockers, Biphenyl Compounds, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Humans, Irbesartan, Kidney, Male, Middle Aged, Office Visits, Prospective Studies, Tetrazoles, Treatment Outcome
Show Abstract · Added October 28, 2014
BACKGROUND - Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy.
STUDY DESIGN - Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study.
SETTING & PARTICIPANTS - 2,739 participants with type 2 diabetes and nephropathy with at least 1 year of blood pressure measurements available.
PREDICTORS - Systolic blood pressure visit-to-visit variability was calculated from the SD of the systolic blood pressure from 4 visits occurring 3-12 months postrandomization.
OUTCOMES - The kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death; the cardiovascular outcome was defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization.
RESULTS - Mean visit-to-visit variability in systolic blood pressure from 3 to 12 months postrandomization was 12.0±6.8(SD)mmHg. Following this ascertainment period, there were 954 kidney disease and 542 cardiovascular events. Greater systolic blood pressure visit-to-visit variability was associated independently with increased risk of the composite kidney disease end point (HR per 1-SD increment, 1.08 [95%CI, 1.01-1.16]; P=0.02) and end-stage renal disease, but not with the cardiovascular outcome.
LIMITATIONS - Observational study with the potential for confounding.
CONCLUSIONS - In diabetic individuals with nephropathy, systolic blood pressure visit-to-visit variability is associated independently with hard kidney disease outcomes.
Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Optimizing blood pressure control in patients with nondiabetic glomerular disease.
Umanath K, Lewis JB, Dwyer JP
(2014) Adv Chronic Kidney Dis 21: 200-4
MeSH Terms: Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Diet, Sodium-Restricted, Humans, Hypertension, Patient Care Planning, Proteinuria, Renal Insufficiency, Chronic, Severity of Illness Index, Smoking Cessation
Show Abstract · Added October 28, 2014
Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD.
Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Estimated GFR decline as a surrogate end point for kidney failure: a post hoc analysis from the Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study and Irbesartan Diabetic Nephropathy Trial (IDNT).
Lambers Heerspink HJ, Weldegiorgis M, Inker LA, Gansevoort R, Parving HH, Dwyer JP, Mondal H, Coresh J, Greene T, Levey AS, de Zeeuw D
(2014) Am J Kidney Dis 63: 244-50
MeSH Terms: Aged, Angiotensin II Type 1 Receptor Blockers, Biomarkers, Biphenyl Compounds, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Irbesartan, Kidney Failure, Chronic, Losartan, Male, Middle Aged, Tetrazoles
Show Abstract · Added October 28, 2014
BACKGROUND - A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defined by smaller declines in eGFR would improve the statistical power of these clinical trials.
STUDY DESIGN - Post hoc analyses of 2 multinational randomized controlled trials (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan [RENAAL] and Irbesartan Diabetic Nephropathy Trial [IDNT]) that assessed the treatment effect of the angiotensin receptor blockers (ARBs) losartan and irbesartan.
SETTING & PARTICIPANTS - 1,513 (RENAAL) and 1,715 (IDNT) adult patients with type 2 diabetes and nephropathy.
PREDICTOR - Established versus alternative end points defined as a confirmed doubling of serum creatinine level versus confirmed eGFR decline of 57%, 40%, 30%, or 20% as a component of a composite end point of end-stage renal disease or eGFR < 15mL/min/1.73m(2).
OUTCOMES - Numbers of patients reaching end points, precision (standard error), and significance (z score) of ARB treatment effect (HR) during follow-up.
RESULTS - Lesser eGFR declines resulted in a greater number of patients reaching end points in both treatment groups and lower standard error of the HR, but the effect on z score was counterbalanced by attenuation of the HR. When calculating the eGFR decline from month 3, attenuation of the HR was less pronounced.
LIMITATIONS - Post hoc analysis.
CONCLUSIONS - Despite increases in precision of the treatment effect, eGFR declines less than a doubling of serum creatinine value did not consistently improve statistical power of the clinical trials due to attenuation of the treatment effect. Attenuation of the treatment effect appears to be due in part to acute effects of ARBs on eGFR. These findings should be taken into account when using lesser eGFR declines as alternative end points for clinical trials.
Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Impaired systolic function by strain imaging in heart failure with preserved ejection fraction.
Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Claggett B, Pieske B, Zile MR, Voors AA, Lefkowitz MP, Packer M, McMurray JJ, Solomon SD, PARAMOUNT Investigators
(2014) J Am Coll Cardiol 63: 447-56
MeSH Terms: Aged, Aged, 80 and over, Aminobutyrates, Angiotensin II Type 1 Receptor Blockers, Drug Combinations, Echocardiography, Doppler, Color, Female, Follow-Up Studies, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Neprilysin, Prognosis, Prospective Studies, Stroke Volume, Tetrazoles, Valine, Valsartan, Ventricular Function, Left
Show Abstract · Added February 28, 2014
OBJECTIVES - This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF).
BACKGROUND - Although diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined.
METHODS - We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined.
RESULTS - The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (-20.0 ± 2.1 and -17.07 ± 2.04 vs. -14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (-27.1 ± 3.1 and -30.1 ± 3.5 vs. -22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = -0.46; p < 0.0001; CS, R = -0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001).
CONCLUSIONS - Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588).
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Angiotensin II, independent of plasma renin activity, contributes to the hypertension of autonomic failure.
Arnold AC, Okamoto LE, Gamboa A, Shibao C, Raj SR, Robertson D, Biaggioni I
(2013) Hypertension 61: 701-6
MeSH Terms: Aged, Aldosterone, Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Antihypertensive Agents, Captopril, Double-Blind Method, Female, Humans, Hypertension, Losartan, Male, Middle Aged, Orthostatic Intolerance, Pure Autonomic Failure, Renin, Sodium
Show Abstract · Added December 10, 2013
At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. Although the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable, suggesting renin-angiotensin (Ang) pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that Ang II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating Ang II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/mL, n=11) compared with matched healthy controls (27±4 pg/mL, n=10; P=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/mL per hour, respectively; P=0.449). To determine the contribution of Ang II to supine hypertension in these patients, we administered the AT(1) receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mm Hg at 6 hours after administration (P<0.05), decreased nocturnal urinary sodium excretion (P=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of captopril on supine blood pressure in a subset of these patients. These findings suggest that Ang II formation in autonomic failure is independent of plasma renin activity, and perhaps Ang-converting enzyme. Furthermore, these studies suggest that elevations in Ang II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT(1) receptor blockers for treatment of these patients.
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1 Members
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17 MeSH Terms