Reduction of proteinuria with angiotensin receptor blockers

Galle, Jan

doi:10.1038/ncpcardio0806

Cited by 42 publications

(43 citation statements)

References 43 publications

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“…Reducing proteinuria is critically important for the regression of chronic kidney disease including diabetic nephropathy, 29 and evidence indicates that ARB not only prevents progression but also induces a reversal of diabetic nephropathy, mainly by reducing proteinuria. 22 The results of this study show that decreases in the mean ambulatory BP levels during both day and night were accompanied by decreases in short-term BP variability by telmisartan. Thus, it is likely that telmisartan is effective for the improvement of short-term BP variability in addition to its general BP-lowering effect in hypertensive patients with overt diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 57%

“…The Ang II type 1 receptor (AT1 receptor) is responsible for most of the pathophysiological actions of Ang II, and AT1 receptor blockers (ARBs) have been shown to exert various protective effects on diabetic nephropathy and its cardiovascular complications, at least partially, through a reduction in urinary protein excretion. 22 However, there have been no studies examining the effects of ARB on short-term BP variability and comparing the associations of BP variability with urinary protein excretion and atherosclerosis in hypertensive patients with type II diabetes. Furthermore, previous studies have reported that telmisartan has a long-term half-life with peroxisome proliferator-activated receptor-g-activating property and a recent AMADEO study showed that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

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Effects of angiotensin II type 1 receptor blocker on ambulatory blood pressure variability in hypertensive patients with overt diabetic nephropathy

et al. 2009

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Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether the angiotensin II type 1 receptor blocker (ARB) would improve ambulatory shortterm BP variability in hypertensive patients with diabetic nephropathy. A total of 30 patients with type II diabetes, along with hypertension and overt nephropathy, were enrolled in this randomized, two-period, crossover trial of 12 weeks of treatment with losartan (50 mg daily) and telmisartan (40 mg daily). At baseline and at the end of each treatment period, 24-h ambulatory BP monitoring with power spectral analysis of heart rate and measurements of proteinuria, estimated glomerular filtration rate and brachial-ankle pulse wave velocity (baPWV) were performed. After 12 weeks of treatment, 24-h, daytime and nighttime shortterm BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased by telmisartan. Both losartan and telmisartan reduced urinary protein excretion and baPWV. However, compared with losartan, telmisartan significantly decreased urinary protein excretion, baPWV and low-frequency (LF)-to-high-frequency (HF) ratio, an index of sympathovagal balance. Multiple regression analysis showed significant correlations between urinary protein excretion and baPWV, 24-h LF-to-HF ratio, nighttime systolic BP and 24-h short-term systolic BP variability. These results suggest that ARB, particularly telmisartan, is effective in reducing proteinuria in hypertensive patients with overt diabetic nephropathy, partly through inhibitory effects on ambulatory short-term BP variability and sympathetic nerve activity, in addition to its longer duration of action on nighttime BP reduction.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Effects of angiotensin II type 1 receptor blocker on ambulatory blood pressure variability in hypertensive patients with overt diabetic nephropathy

et al. 2009

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“…For example, studies have demonstrated superiority of ultrahigh dose ARB therapy in the management of chronic renal disease, when compared with typical antihypertensive regimens and independent of any apparent hemodynamic influence. 41 Trials of combined and monotherapy with ultrahigh dosing of losartan or newer generation ARBs seem warranted in MFS. Such initiatives may ultimately be informed by the nature of the underlying mutation, consideration of other potential genetic influences (eg, those influencing drug metabolism, affinity for targets, and downstream consequences), and the application of biomarkers of drug response and efficacy.…”

Section: Perspectivementioning

confidence: 99%

Potential Phenotype–Genotype Correlation in Marfan Syndrome

Dietz

2015

Circ Cardiovasc Genet

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A recent emphasis on individualized medicine reflects a desire to transition currently prevailing evidence-based practices (What works best for the average patient?) to more informed and tailored approaches (What will work best for this patient or subgroup?). It has been both expected and realized that genotypic information will contribute prominently to this endeavor. In this issue of Circulation Cardiovascular Genetics, Franken et al 1 report that the angiotensin receptor blocker (ARB) losartan is particularly effective at suppressing aortic root aneurysm progression in patients with Marfan syndrome (MFS) that are heterozygous for mutations in the fibrillin-1 gene (FBN1) that create a premature termination codon, when compared with other mutation classes expected to express abnormal protein from the mutant allele. Given the intuitive importance of this finding, it is worth exploring its potential biological foundations, while also considering alternative explanations. Article see p 383 Proposed Pathogenesis of MFSMFS is an autosomal-dominant systemic disorder of connective tissue with prominent involvement of the ocular, skeletal, and cardiovascular systems, including a strong predisposition for eye lens dislocation (ectopia lentis) and myopia, long-bone overgrowth and other skeletal deformity, and progressive aortic root dilatation and tear (dissection), respectively. The condition is caused by heterozygous mutations in FBN1 that encodes the extracellular matrix protein fibrillin-1. Fibrillin-1 monomers aggregate to form complex extracellular structures called microfibrils and an extracellular deficiency of microfibrils is thought to be the sentinel event in MFS pathogenesis. Missense mutations are the most common type causing MFS, with particularly high frequency of substitutions that either destroy or create cysteine residues in repetitive epidermal growth factor-like or latent transforming growth factor-β (TGF-β)-binding protein-like domains that each have 6 or 8 obligate cysteines with predictable spacing, respectively, that are required for proper intradomain folding. The FBN1 mutational repertoire also includes all other types of mutations, including insertions/deletions (indels) or altered splicing events that alter the coding sequence but maintain the open reading frame and events that create a premature termination codon, including nonsense and frameshift mutations and out-of-frame perturbations of splicing. Finally, a small subset of patients with MFS show large deletions that remove most or all of the disrupted allele. Premature termination codon mutations in FBN1 that disrupt the open reading frame before the distal portion of the penultimate are expected and observed to induce instability and efficient clearance of the mutant mRNA through nonsense-mediated mRNA decay, effectively precluding the production of much (or any) abnormal fibrillin-1 protein. Cell lines and tissues from patients and mouse models with MFS show diminished matrix deposition of fibrillin-1, with levels <50% threshold predict...

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“…Blockade of RAAS in diabetic kidney disease and overt nephropathy. 17 Current management consensus statements from the National Kidney Foundation (NKF)/ Kidney Disease Outcomes Quality Initiative (KDOQI), 10 American Diabetes Association (ADA), 1 and Joint National Committee (JNC) VII 18 advocate the use of ARBs for management of patients with hypertension and DKD, even in those with advanced stages of nephropathy as well as in those with microalbuminuria. ARBs have been shown to exert their benefi cial effect by blood pressure reduction, improving endothelial dysfunction and reducing oxidative stress.…”

Section: Role Of Drugs Blocking Raasmentioning

confidence: 99%

“…ARBs have been shown to exert their benefi cial effect by blood pressure reduction, improving endothelial dysfunction and reducing oxidative stress. 17 Data from the Heart Outcomes Prevention Evaluation (HOPE) Study evaluated microalbuminuria as a progressive manifestation of overt type nephropathy in patients with type 2 diabetes as a secondary endpoint. 19 Ramipril was shown to reduce the onset of overt nephropathy by 22%.…”

Section: Role Of Drugs Blocking Raasmentioning

confidence: 99%

Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study

Bichu

Nistala²,

Khan³

et al. 2008

VHRM

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Diabetic kidney disease is characterized by persistent albuminuria (Ͼ300 mg/dl or Ͼ200 μg/min) that is confi rmed on at least 2 occasions 3 to 6 months apart, with a progressive decline in the glomerular fi ltration rate (GFR), elevated arterial blood pressure, and an increased risk for cardiovascular morbidity and mortality. Diabetic kidney disease is the leading cause of end stage renal disease (ESRD) prompting investigators to evaluate mechanisms by which to slow disease progression. One such mechanism is to block the activity of angiotensin II at the receptor site and agents that follow this mechanism are referred to as angiotensin receptor blockers (ARB). There is suffi cient clinical evidence to support that ARB have protective effects on kidney function in patients with diabetes and hypertension. However, in the past decade there have been few investigations comparing individual ARBs on renal outcomes. Telmisartan, a lipophilic ARB with a long half-life, has been hypothesized to have a greater anti-proteinuric effect when compared to the shorter acting losartan. Therefore, the A comparison of telMisartan versus losArtan in hypertensive type 2 DiabEtic patients with Overt nephropathy (AMADEO) trial sought to investigate renal and cardiovascular endpoints. In this review, we discuss the pathophysiology of diabetic kidney disease and implications of the AMADEO trial in the context of current understanding from recent outcome trials.

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Reduction of proteinuria with angiotensin receptor blockers

Cited by 42 publications

References 43 publications

Effects of angiotensin II type 1 receptor blocker on ambulatory blood pressure variability in hypertensive patients with overt diabetic nephropathy

Effects of angiotensin II type 1 receptor blocker on ambulatory blood pressure variability in hypertensive patients with overt diabetic nephropathy

Potential Phenotype–Genotype Correlation in Marfan Syndrome

Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study

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