lncRNAs as a Biomarker to Assess the Therapeutic Impact of Oral Absorbent ± Probiotics in CKD Patients With PAD

This is a prospective, randomized, open-labeled, blinded end-point (so called PROBE) trial for 6 months. All patients presented to the clinics of participating sites with advanced CKD with eGFR 15 < eGFR < 60 ml/min/1.73m2 and symptomatic PAD will be screened for eligibility. The other healthy adults will be enrolled as control.

Participants who fulfill the inclusion/exclusion criteria will be invited to participate in the current study. After the participants provides the written informed consents, detailed demographic data including genders, ages, body weights, body heights, smoking status (never, past, or active), the baseline creatinine (the nadir value in the past three months) and its corresponding eGFR and CKD stages, degrees of albuminuria (Urine albumin creatinine ratio, UACR), NYHA functional class, presence of atrial fibrillation, prior cardiovascular disease (CVD, including myocardial infarct, peripheral arterial occlusive diseases), presence of diabetes mellitus (DM), or hypertension. Detailed medication list will also be obtained, with the focus on angiotensin receptor blocker or angiotensin converting enzyme inhibitors, statins, and beta-blockers.

The etiology of kidney injury will be non-mutual-exclusively categorized as:

• Hypertensive kidney disease, participants who received any kind of anti-hypertensive drugs.
• Diabetic kidney disease, patients who received any kind of anti-diabetics drugs.
• Glomerulonephritis, patients who have proteinuria more than 0.5mg/dL and kidney biopsy approved Glomerulonephritis.

Eligible 120 participants (group I) with eGFR 15 < eGFR < 60 ml/min/1.73m2 and symptomatic PAD will be randomized into ABC-treatment (A) or no-treatment (B)participants with a 1:1 ratio. The other 60 eligible controls (eGFR > 60 ml/min/1.73m2 and no PAD, group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The participants will receive CharXenPlus 4g (with ABC 2g) thrice daily for 6 months in subgroups IA and IIA, while the participants in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the participants will receive probiotics APL-MIX2 (CharXprob) 0.8 g once a day in the last 3 months except those in subsubgroups IAb and IBb.

After being processed, urine, stool, and plasma samples will be stored in -80°C for further examinations. The names and chart numbers participants will be masked to provide adequate privacy. The coding book connecting codes and individual participants will be filed separately in order to protect participants' privacy. participants will be asked if investigators can keep the encrypted samples refrigerated for 10 years for further investigations.

Inclusion criteria

I: Patients

• Age > 20 years old on the day of screening.
• CKD patients with eGFR 15 < eGFR < 60 ml/min/1.73m2 in a stable status, creatinine elevated less than 0.3 mg/dL in at least 30 days before enrollment.
• Symptomatic PAD with Rutherford Stage ≥ 2 and ABI < 0.9 (or documented by CT-angio, vascular duplex, etc.).

II: Controls

• Age > 20 years old on the day of screening.
• With eGFR > 60 ml/min/1.73m2
• No clinical PAD.

Exclusion criteria

• Baseline estimated glomerular filtration rates (eGFR) < 15 ml/min/1.73m2 according to MDRD equation.
• Patients in severe malnutrition status, albumin less than 2.0 g/dL
• Patients in severe anemia or active gastrointestinal bleeding with hemoglobulin < 8 g/dL.
• Peptic ulcer, esophageal varices, ileus or under fasting status
• Previous gastrointestinal operation.
• Chronic constipation, as defined with less than 3 bowel movements per week, straining, hard stools, incomplete evacuation and inability to pass stool. If usage of oral laxatives can achieve bowel movement, this patient will not be excluded.
• Patients with major hemorrhage, as defined with acute hemorrhage and requirement of blood transfusion during index admission.
• Patients with a biopsy proved or clinically diagnosed advanced liver cirrhosis, Child classification B or C.
• Solid organ or hematological transplantation recipients.
• Patients with oliguric kidney injury, as defined with less than 500 cc/day.
• Evidence of obstructive kidney injury or polycystic kidney disease.
• Antibiotics or probiotics treatment within the last 2 weeks before enrollment and during follow-up period.