Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of an Oral Nutritional Supplement on Nutritional and Functional Status, Biological Markers (Inflammation and Oxidative Stress, Intestinal Microbiota, Circulating microRNA and Its Target Genes) in Malnourished Hemodialysis Patients.
Brief Summary: Malnutrition in hemodialysis patients is frequent and it is associated with a reduction in muscular mass, strength, functional capacity and quality of life, with an increment in inflammatory and oxidative markers, and with a dysregulation of circulating miRNAs and its target genes.

Animal and human studies have reported that some dietary components (macronutrients, micronutrients and other bioactive substances) might restore these altered features.

Thus, we hypothesized that the intake of an oral nutritional supplement (ONS) specifically developed for malnourished hemodialysis patients enriched with functional nutrients (extra virgin olive oil, omega 3 fatty acids, whey protein, antioxidants, carnitine, and with or without probiotics) vs. individualized diet recommendations might:

* Improve nutritional status (visceral proteins, muscular mass), functional capacity and quality of life.
* Reduce inflammatory and oxidative markers, and modulate the circulating levels of some miRNAs and the expression of its target genes on cells. miRNAs may be useful biomarkers to check the response to a nutritional intervention in malnourished hemodialysis patients.

The present study is a randomized, multicenter, parallel-group trial with 3 groups, open to the intake of ONS or individualized diet recommendations, but double-blind to the intake of probiotics. Inclusion criteria comprised adult subjects (\>18 y/o) undergoing hemodialysis more than 6 months previous at inclusion and at least one of these caloric malnutrition criteria: a) involuntary weight loss \>5% in 3 months or \>10% in 6 months; b) serum albumin \< 3.5 g/dl or prealbumin \<28 mg/dl; c) body mass index (BMI) \< 23 kg/m2; d) muscular mass loss \>5% in 3 months or \>10% in 6 months.

The study duration is 6 months, and comprises 4 visits (screening, basal, 3 months and 6 months). A nutritional examination that included anthropometric measurements, handgrip strength measured by a hand dynamometer, body composition assessed by bioelectrical impedance analysis (BIA) and a 5 days dietary record; quality of life evaluation by the "12-item short form health survey"; the presence of symptoms of depression and anxiety (Hospital Anxiety and Depression Scale); assessment of functional status by the "Barthel" test, the "Short Physical Performance Battery" and the "International Physical Activity Questionnaire"; and blood and stool samples will be obtained for each participant in each study visit (except screening visit).


Options:
A: Inclusion Criteria:

* Adult subjects (\>18 y/o) undergoing hemodialysis more than 6 months previous at inclusion.
* At least one of these caloric malnutrition criteria: a) involuntary weight loss \>5% in 3 months or \>10% in 6 months; b) serum albumin \< 3.5 g/dl or prealbumin \<28 mg/dl; c) body mass index (BMI) \< 23 kg/m2; d) muscular mass loss \>5% in 3 months or \>10% in 6 months.
* Standard hemodialysis therapy (3 days/week, 240 min, high permeability dialyzer, blood flow \>250 ml/min and dialysate flow 500 ml/min) or on-line hemodialysis therapy that was not modified in the last 3 months previous to the inclusion.
* Written informed consent obtained.

Exclusion Criteria:

* Type 1 diabetes mellitus or type 2 diabetes mellitus with HbA1c\>9%.
* Unstable dry weight.
* Limb amputation.
* Significant edema.
* Active malignancy.
* Hospital admissions in the last 3 months.
* Acute gastrointestinal disease in the 2 weeks before the inclusion.
* Gastrectomy, gastroparesis or abnormal gastric emptying.
* Acute heart failure grade IV.
* Severe hepatic insufficiency (men gamma glutamyl transferase -GGT- \>150 U/l, women \>120 U/l).
* Alcohol or other drugs abuse.
* Participants enrolled in other research study at inclusion.
* Pregnant women.
* No informed consent obtained.
* Patients who received any oral nutritional supplement (specific for hemodialysis patients or not) in the 4 weeks before the inclusion.
* Patients receiving enteral tube feeding.
* Galactosemia, fructosemia, or requirement of a no fiber diet.
* Allergy or hypersensitivity to any ingredient of the oral nutritional supplement.
* Ongoing treatment with glucocorticoids.
* Patients who received any oral fatty acids omega-3 supplement in the 4 weeks before the inclusion.
* Patients who received intradialytic parenteral nutrition in the 3 months before the inclusion.
* Patients who received any probiotics or prebiotics (not as part of the diet) in the 3 months before the inclusion.
* Anemia (Hemoglobin \< 10 g/dl) or Epoetin resistance.
B: Inclusion Criteria:

1. Age ≥18 years
2. Have a diagnosis of ESRD and have been on Continuous Ambulatory Peritoneal Dialysis (CAPD) for at least 3 months
3. Be in a stable clinical condition during the four weeks immediately prior to Screening Period as demonstrated by medical history, physical examination and laboratory testing
4. Have a blood hemoglobin concentration above 8,5 g/100ml (data will be verified with Investigators)
5. Have not experienced peritonitis episodes in the last 3 months
6. Be treated with Extraneal (nocturnal exchange bag solution) for at least 1 month
7. Be treated with 3 diurnal exchange bag solutions (1.5% or 2.5% glucose) and one nocturnal exchange bag solution (Extraneal)
8. Have Kt/V urea measurement \> 1.7 per week in a previous test performed within 6 months that should be confirmed at Baseline Visit
9. Have a minimum weekly creatinine clearance of 45 litres in a previous test performed within 6 months that should be confirmed at Baseline Visit
10. Have a D/P Creatinine ratio at Peritoneal Equilibration Test (PET) between 0.50 and 0.81 in a previous test performed within 6 months that should be confirmed at Baseline Visit
11. Have a D/P Glucose ratio at Peritoneal Equilibration Test (PET) between 0.26 and 0.49 in a previous test performed within 6 months that should be confirmed at Baseline Visit
12. Be treated by the participating clinical Investigator for a period of at least three months
13. Have understood and signed the Informed Consent Form.

Exclusion Criteria:

1. Have a history of drug or alcohol abuse in the six months prior to entering the protocol
2. Be in treatment with androgens
3. Have Diabetes Mellitus (as defined by the American Diabetes Society, objectively documented by a fasting plasma glucose and HbA1c determinations)
4. Have clinically significant abnormal liver function test (SGOT, SGPT, and gamma-GT \> 2 times the upper normal limit)
5. Have acute infectious conditions (i.e.: pulmonary infection, acute hepatitis, high or low urinary tract infections, renal parenchymal infection, pericarditis, etc)
6. Have a history of congestive heart failure and clinically significant arrhythmia
7. Have an history of epilepsy or any NCS disease
8. Have malignancy within the past 5 years, including lymphoproliferative disorders
9. Have any medical condition that, in the judgment of the Investigator, would jeopardize the patient's safety following exposure to study drug, particularly if patient's life expectancy is less than 1 year
10. Have a history of L-Carnitine therapy or use in the month prior to entering the protocol
11. Have used any investigational drug in the 3 months prior to entering the protocol
12. Be in pregnancy, lactation, fertility age without protection against pregnancy by adequate contraceptive means
C: Inclusion Criteria:

* HD \>3 months
* Fluid overload ≥15% of extracellular volume (ECV) predialysis, as determined by BCM-measurement, after one of the 2 the midweek interdialytic intervals
* Informed consent of the patient

Exclusion Criteria:

* none, except those specified by the Declaration of Helsinki
D: Inclusion Criteria:

* Patient with less than 1 month on hemodialysis.
* Treated with rHuEPO.
* Male or female aged of more than 18 years old.
* With contraception treatment for women of procreation age.
* Having received and understand information.

Exclusion Criteria:

* Patients with no need of rHuEPO
* Patients with cancer disease
* Patients with life expectancy under 6 months
* Patients having a proved carnitine deficiency before the start of hemodialysis

Answer: A