Evaluation of the Effect of a Daily Dose of Wakame (Undaria Pinnatifida) on Reducing Circulating Concentrations of Advanced Glycation End Products (AGEs: Methylglyoxal) in Patients With Stage III Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Circulating AGE
研究概览
简要总结
Persistent glomerular hyperfiltration is a characteristic feature of the early stages of kidney disease and represents a factor in the progression of chronic kidney disease (CKD). In this context, the benefit of low-protein diets (less than 0.8g/kg/day) has been demonstrated in slowing the progression of CKD, although the underlying pathophysiological mechanisms remain unclear.
Some studies suggest that the effects of protein on renal hemodynamics are primarily linked to the quality of the protein, particularly the amount of AGEs (Advanced Glycation End Products) consumed.
Recently, edible seaweeds have gained popularity in Western countries due to their anti-inflammatory, anti-diabetic, and antihypertensive properties. These seaweeds are also associated with the above-average longevity of certain Asian populations who consume them daily. Wakame seaweed (Undaria pinnatifida), which is locally harvested along the French Atlantic coast, has shown promising biological properties, notably antihypertensive and anti-diabetic effects. It has also been recently demonstrated that fucoxanthin, a compound found in high concentrations in wakame, possesses strong anti-AGE activity.
Dietary modifications are essential for nephroprotection, but they are often difficult to implement. This highlights the need to develop approaches that are both acceptable on a daily basis and sustainable in the long term for patients.
A Michelin-starred chef, known for regularly incorporating seaweed into his cuisine, is a sponsor of the project and has validated a set of adapted recipes that will be offered to participants to accompany the daily wakame supplementation.
The investigator's hypothesis is that a daily dose (5 grams of French wakame, dehydrated at low temperature and in flake form), equivalent to the average daily intake in Japan, could reduce circulating AGE levels in patients with stage III CKD. This would provide an additional protective effect when combined with the standard low-protein diet, helping to slow the progression of CKD over the long term.
详细描述
Persistent glomerular hyperfiltration is a characteristic feature of the early stages of chronic kidney disease (CKD), particularly observed in the initial phases of diabetic nephropathy, and constitutes a major factor in the progression of kidney failure. In this context, the benefit of low-protein diets (less than 0.8g/kg/day) in slowing CKD progression has been demonstrated, though the underlying pathophysiological explanation remains unclear.
Among the proposed mechanisms, a study demonstrated that an oral protein load (cooked red meat) led to a significant 26% increase in glomerular filtration rate, measured by inulin clearance, in healthy subjects 90 minutes after ingestion. This protein-induced glomerular hyperfiltration is used to assess renal functional reserve, defined as the kidney's ability to increase renal blood flow and GFR after a protein load, via modulation of intrarenal hemodynamics.
The precise mechanisms underlying these hemodynamic and functional changes remain controversial. A study suggested that the renal hemodynamic effects of a protein load are primarily related to the amount of Advanced Glycation End Products (AGEs) ingested. Indeed, the experimental models used to study renal functional reserve (e.g., amino acid perfusions, red meat meals) also involved significant AGE exposure.
AGEs are formed through non-enzymatic glycation reactions, where sugars bind to peptides or nucleic acids, leading to cellular aging via increased ROS (Reactive Oxygen Species) production and activation of inflammatory pathways. Methylglyoxal (MG) and Carboxymethyl-lysine (CML), two major circulating and tissue AGEs, are predominantly cleared by the kidneys and accumulate with age.
While it was previously thought that AGEs were primarily endogenously produced, it is now well established that dietary intake is a significant source, especially via harmful cooking methods (high-temperature cooking with oil and little water), both in healthy individuals and those with CKD. An oral AGE load has been shown to significantly increase circulating CML levels within 90 minutes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients not under legal protection
- •Patients aged ≥ 18 and < 90 years
- •Patients with stage IIIA-B chronic kidney disease (CKD) (estimated GFR by CKD-EPI ≥ 30 mL/min and < 60 mL/min)
- •Patients receiving optimized nephroprotective treatment (ACE inhibitors, SGLT2 inhibitors)
- •Patients who have signed the informed consent form
- •Patients not participating in another clinical study
- •Patients affiliated with or benefiting from a social security scheme
排除标准
- •Adult patients under legal protection
- •Patients under 18 years old or over 90 years old
- •Patients with uncontrolled thyroid disorders
- •Patients with decompensated heart failure
- •Patients consuming other dietary supplements containing seaweed or iodine (e.g., multivitamins)
- •Pregnant or breastfeeding women
- •Patients with acute kidney injury
- •Patients who decline to participate in the study
结局指标
主要结局
Circulating AGE
时间窗: From enrollment to the end of 3 months follow-up
Circulating AGE measurement by plasma methylglyoxal (MG) measurement at M3
次要结局
- Proteinuria(From enrollment to the end of 3 months follow-up)
- Ambulatory blood pressure(From enrollment to the end of 3 months follow-up)
- Plasma creatinine clearance(From enrollment to the end of 3 months follow-up)
- HbA1c(From enrollment to the end of 3 months follow-up)
- Lipid profile(From enrollment to the end of 3 months follow-up)
- TSH(From enrollment to the end of 3 months follow-up)