Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 310
- 试验地点
- 1
- 主要终点
- normalization of serum LDL cholesterol
研究概览
简要总结
Hyperlipidemia and atherosclerosis lead to cardiovascular diseases and are an indirect cause of increased death rate in the general population. This association is still more evident in specific subpopulations, like patients with advanced chronic kidney disease (CKD), especially hemodialysis (HD) patients, due to a higher prevalence of lipid disturbances and atherosclerosis compared to the general population. Cardiovascular events in CKD patients are frequently associated with traditional risk factors, including diabetes, male sex, hypertension, dyslipidemia and advanced age. However, these factors failed to fully account for the increased risk of cardiovascular events in CKD. The efforts are made to identify new risk factors that contribute to the development of atherosclerosis and participate in causes of cardiovascular death. In 2003, there were identified peptides designated salusin-alpha and salusin-beta. Development of atherosclerosis may be suppressed by salusin-alpha. Salusin-alpha may have a lipid lowering effect, similar to that of statins.
The purpose of this study is to investigate whether 1) salusin-alpha is associated with lipid metabolism of HD patients (without or with metabolic syndrome or type 2 diabetes mellitus), similarly or not like in healthy or obese subjects; 2) treatment with atorvastatin and its effects are associated with changes in plasma salusin-alpha concentration, if so - whether it is dependent on the direct influence of atorvastatin on salusin-alpha or associated with a decrease in serum lipid level; 3) salusin-alpha may predict mortality in HD patients.
详细描述
Purpose I, step 1. To investigate whether plasma salusin-alpha is associated with lipid and lipid-related abnormalities in hemodialysis (HD) patients, plasma salusin-alpha concentration, expression of receptor CD36 on macrophages, serum lipid parameters, anthropometric and laboratory indices of nutrition and biomarkers of inflammation will be cross-sectionally analyzed. In chronic kidney disease (CKD) patients there is a close association between atherosclerosis (A), malnutrition (M) and inflammation (I), known as MIA syndrome, so interactions between all these parameters will be obviously present and should be taken into account. In addition, homeostasis model assessment of insulin resistance (HOMA-IR) will be applied as insulin resistance is a metabolic abnormality occurring in advanced CKD, in metabolic syndrome shown in about 50% of HD patients and diabetic mellitus (DM), being a cause of CKD in approximately 40% of cases. Results of correlations and associations shown in HD patients will be compared with those of healthy controls and obese persons with normal renal function for evaluation of salusin-alpha relationships under different metabolic conditions, which may exert not uniform influence.
Study populations:
HD patients (n = 200) Obese persons (n = 50) Controls (n = 60)
Data collection:
Medical history (with special attention for demographics - age, gender, cause of CKD, renal replacement therapy vintage, changes in body weight, habits and data required for inclusion and exclusion criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For HD patients:
- •HD vintage at least 3 months
- •signed consent for participation in the study
- •For obese persons:
- •BMI > 30 kg/m2
- •eGFR > 60 ml/min/1.73 m2 BSA
- •interest in weight loss according to weight loss diet protocol (WLDP)
- •signed consent for participation in the study
- •For controls (healthy volunteers):
- •declared health, comfort
- •no substantial changes in the medical interview and physical examination
- •no medication
- •signed consent for participation in the study
排除标准
- •For HD patients:
- •active thyroid gland disease and/or thyreotropic medication
- •treatment with corticosteroids, immunosuppressants or hormones
- •treatment with statins or fibrates in 6 weeks before the study commencement
- •diagnosis of genetic lipid abnormalities
- •neoplastic disease
- •acute coronary syndrome and/or cerebral stroke in 6 months before the study commencement
- •surgery in 3 months before the study commencement
- •plasma activities of ALT and/or AST exceeding 3 times the upper laboratory normal limit
- •non compensated diabetes mellitus
- •For obese persons:
- •a known history of moderate or severe cardiovascular disease, stroke or transient ischemic attack
- •uncontrolled hypertension
- •severe dyslipidemia (triglycerides > 500 mg/dl, total cholesterol > 350 mg/dl) or taking lipid-lowering agents at the recruitment or 6 weeks before
- •serious chronic disease requiring active treatment (example with glucocorticoids, antineoplastic agents, psychoactive agents, bronchodilators on a regular basis, insulin or oral hypoglycemic drugs)
- •women of child-bearing potential using an effective form of hormonal birth control, pregnant or lactating women
研究组 & 干预措施
atorvastatin
The prospective, randomized, double-blind, placebo-controlled study:
- will be preceded by one month non-pharmacological treatment of hyperlipidemia (prerandomization phase)
- 130 hyperlipidemic hemodialysis (HD) patients will be randomly assigned to receive blinded study drug: 65 patients will be allocated to start with atorvastatin and 65 patients - with placebo.
Atorvastatin will be administered and monitored according to the K/DOQI guidelines (2003).
The prospective, observational study:
- 35 hyperlipidemic patients will be followed for 30 weeks on the prescribed non-pharmacological treatment of hyperlipidemia
干预措施: Atorvastatin (Drug)
结局指标
主要结局
normalization of serum LDL cholesterol
时间窗: 30 weeks
次要结局
未报告次要终点
研究者
Alicja E. Grzegorzewska
Full Professor
Poznan University of Medical Sciences