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Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors.

ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) is a key mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II) and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin inhibitors (DRIs) and is approved for the treatment of hypertension in humans. It effectively reduces BP in the general population of hypertensive patients and has a tolerability and safety profile similar to placebo. Aliskiren has favorable effects on vascular inflammation and remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality.

SUBMITTER: Pimenta E

PROVIDER: S-EPMC2701487 | biostudies-other | 2009 Jun

REPOSITORIES: biostudies-other

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Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors.

Pimenta Eduardo E Oparil Suzanne S

Therapeutics and clinical risk management 20090622 3

The renin-angiotensin-aldosterone system (RAAS) is a key mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II) and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin i ...[more]

PMID: 19707255

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Project description:BackgroundGlycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS). Damaged glycocalyx may represent microvascular damage in diabetes and assessment of its dimension might improve early cardio-renal risk stratification.AimTo assess the associations between PBR, PBR-hf and MVHS and cardio-renal risk factors in persons with type 1 diabetes (T1D); and to compare these dimensions in persons with T1D and controls.MethodsCross-sectional study including 161 persons with T1D stratified according to level of albuminuria and 50 healthy controls. The PBR, PBR-hf and MVHS were assessed by the GlycoCheck device (valid measurements were available in 136 (84.5%) with T1D and in all the controls). Higher PBR and PBR-hf indicate smaller glycocalyx width. Lower MVHS represents a worse microvascular health.ResultsThere were no associations between PBR, PBR-hf or MVHS and the cardio-renal risk factors in persons with T1D, except for higher PBR-hf and lower MVHS in females (p = 0.01 for both). There was no difference in PBR, PBR-hf or MVHS in persons with normo-, micro- or macroalbuminuria. The PBR was higher (2.20±0.30 vs. 2.03±0.18μm; p<0.001) and MVHS lower (3.15±1.25 vs. 3.53±0.86μm; p = 0.02) in persons with T1D compared to controls (p≤0.02). After adjustment for cardio-renal risk factors the difference in PBR remained significant (p = 0.001).ConclusionsThe endothelial glycocalyx dimension was impaired in persons with T1D compared to controls. We found no association between the endothelial glycocalyx dimension and the level of albuminuria or cardio-renal risk factors among persons with T1D. The use of the GlycoCheck device in T1D may not contribute to cardio-renal risk stratification.

Project description:BackgroundNephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. We retrospectively evaluated potential risk factors for cisplatin-induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity.Patients and methodsWe reviewed clinical data for 401 patients who underwent chemotherapy including a high dose (≥60 mg/m2) of cisplatin in the first-line setting. Nephrotoxicity was defined as an increase in the serum creatinine concentration of at least grade 2 during the first course of cisplatin chemotherapy, as assessed on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The severity of nephrotoxicity was evaluated on the basis of the mean change in the serum creatinine level. Magnesium was administered intravenously to 67 patients (17%).ResultsCisplatin-induced nephrotoxicity was observed in 127 patients (32%). Multivariable analysis revealed that an Eastern Cooperative Oncology Group performance status of 2 (risk ratio, 1.876; P = 0.004) and the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio, 1.357; P = 0.047) were significantly associated with an increased risk for cisplatin nephrotoxicity, whereas intravenous magnesium supplementation was associated with a significantly reduced risk for such toxicity (risk ratio, 0.175; P = 0.0004). The development of hypomagnesemia during cisplatin treatment was significantly associated with a greater increase in serum creatinine level (P = 0.0025). Magnesium supplementation therapy was also associated with a significantly reduced severity of renal toxicity (P = 0.012).ConclusionsA relatively poor performance status and the regular use of NSAIDs were significantly associated with cisplatin-induced nephrotoxicity, although the latter association was marginal. Our findings also suggest that the ability of magnesium supplementation to protect against the renal toxicity of cisplatin warrants further investigation in a prospective trial.

Project description:BackgroundObesity is one of the conditions that increases the risk of cardiovascular disease. Studies about obesity trajectory and cardio metabolic outcomes at adulthood are still scarce. Therefore, we aimed to assess the association between patterns of overweight over the life-course and cardio metabolic risk factors in young adults.MethodsIn 1982, the maternity hospitals in Pelotas were visited daily and those newborns whose family lived in the urban area of the city were identified (n = 5914), and have prospectively followed for several occasions. Weight and height were measured at every visit. BMI-for-age z-score was calculated using the WHO Child Growth Standards. Overweight and obesity were defined as a BMI greater than or equal to 25 kg/m2 and 30 kg/m2 respectively. This was the definition adopted for evaluations overweight and obesity at 30 years. The participants were divided into eight groups according to the presence of overweight or obesity in childhood, adolescence and adulthood. Blood pressure, random blood glucose, HDL cholesterol, LDL cholesterol triglycerides and fat mass were measured.ResultsFrom 2219 participants with anthropometric data in childhood, adolescence and adulthood, 25% never had been overweight, whereas 11.6% were overweight in the three periods. Random blood glucose, SBP and DBP were higher among those subjects who were always overweight/ obese or only overweight/obese during adolescence and adulthood. The participants who were never overweight/obese or only in childhood or adolescence had a lower cardiovascular risk profile (higher HDL cholesterol, lower blood pressure, lower random glucose, lower LDL cholesterol) at 30 years. Fat mass captured from 25 to 100% of the association of overweight and obesity trajectory with cardiometabolic risk factors.ConclusionsThe tracking of overweight/obesity is associated with an adverse cardio metabolic profile and this association is largely mediated by fat mass in adulthood.

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Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors.

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Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors.

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