Gut-kidney Axis: Renal Effects of Meditarranean Diet and Low-protein Diet With Ketoacids to Restore Physiological Intestinal Mibrobiota in Chronic Kidney Disease
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change from baseline in fecal microbiota by MD and KD at 18 months
研究概览
简要总结
Food intake has a deep influence on gut microbiota composition and function, both in health and in disease status. In chronic kidney disease (CKD), a microbiota dysbiosis status is observed. Moreover, many toxic uremic molecules are microbial-derived and their accumulation promotes, in turn, disease progression.
Investigators' hypothesis foresees a beneficial effect of nutritional treatments, able to restore gut microbiota balance, to lower microbial-derived uremic toxins and to improve clinical conditions in CKD patients.
Mediterranean Diet (MD) is supposed to have beneficial effect on microbiota composition, while low-protein diet supplemented with ketoacids (KD) is used in CKD patients for the improvement of clinical conditions, but its effects on gut microbiota are currently unknown. Investigators' project aim is to verify the effects of MD and KD on: microbiota and metabolome composition, microbial-derived uremic toxins level and clinical conditions in a cohort of CKD patients.
详细描述
Background: In CKD the biochemical milieu of gastrointestinal tract (GI) is altered by several mechanisms, affecting gut microbiota composition and function. Beyond exerting metabolic functions, microbiota influences the general healthy status. It digests food mainly through saccharolytic or proteolytic catabolism, with a prevalence of the former in healthy status. On the contrary, in CKD, dysbiosis with the prevalence of the latter is observed.
In this setting, reduction in glomerular filtration rate and increase in urea levels result in its heavy influx into the GI. Here urea is hydrolyzed spontaneously and/or by microbial urease, releasing ammonia, readily converted into ammonium hydroxide. The latter raises GI pH, causing mucosa irritation, enterocolitis and changes in microbiota composition. This contributes to worsening of inflammation and disease progression: indeed, microbiota has been identified as the primary source of several well known and yet unidentified volatile organic compounds (VOC), including some of the main uremic toxins.
Some beneficial effects observed from studies with low-protein diet supplemented with ketoacids in CKD cannot be solely explained by the reduced protein intake. Investigators' hypothesis is that ketoacids may have direct protective effects on renal damage progression, through induced modifications in gut biochemical milieu and in microbiota composition.
Similarly, the Mediterranean Diet with its fibers supply can contribute to restore gut microbiota balance.
Hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
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
- •prevalent patients in tertiary nephrology clinic;
- •patients over 18 years;
- •CKD stage 3b-4 (eGFR between 15 and 45 ml/min/1.73m2, estimated by MDRD formula);
- •clinically proven adherence to prescribed therapies;
- •informed consent signed.
排除标准
- •change of GFR >30% within the last 3 months;
- •acute, intercurrent disease during the previous 3 months;
- •severe undernutrition as indicated by: BMI < 20 kg/m2 and serum albumin < 3.2 g/dl, or BMI < 17.5 kg/m2 whatever albumin value, or body weight reduction > 5% within the last month or > 10% within the last six months;
- •pregnancy or feeding;
- •chronic treatment with steroid or cytotoxic drugs; fast progressing glomerulonephritis; active SLE and vasculitis;
- •gastrointestinal diseases (Crohn disease, Ulcerative colitis, Celiac Sprue, Stypsis); 7) infectious diseases; 8) cardiac failure stage III-IV NYHA; advanced liver cirrhosis; active cancer diseases; severe encephalopathy associated with lack of spontaneous feeding; chronic obstructive respiratory diseases needing oxygen treatment; 9) use of antibiotics or probiotics until 15 days before the enrolment; 10) psychiatric disease or inability to assess follow-up.
结局指标
主要结局
Change from baseline in fecal microbiota by MD and KD at 18 months
时间窗: 0-18 months from the beginning of the study
Active fecal microbiota will be analyzed a culture-independent methods. Bacterial tag encoded FLX-titanium amplican pyrosequencing (bTEFAP) analyses will be carried out for bacterial RNA directly extracted from feces at months 0, 3, 9, 12 and 18.
次要结局
- Change from baseline in inflammatory status at 18 months(0-18 months from the beginning of the study)
- Change from baseline in renal function at 18 months(0-18 months from the beginning of the study)
- Change from baseline in nutritional status at 18 months(0-18 months from the beginning of the study)
- Change from baseline in microbial-derived uremic toxins level at 18 months(0-18 months from the beginning of the study)
研究者
Dr Biagio Di Iorio
Chair of Nephrology Departement
Azienda Sanitaria ASL Avellino 2