Effect of Bio-impedance Analysis and Vitamin D vs Usual Care on Left Ventricular Mass in Peritoneal Dialysis Patients: A Randomized Controlled Trial (FLUID Study)

• Combined outcome of death, non-fatal CV event (stroke, MI, amputation, CHF), and transfer to HD for inadequacy or ultrafiltration failure [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
• Volume measures: bio-impedance (RXc graph, vector length, impedance ratio, phase angle, ECW:TBW ratio), weight, N-BNP, mean and pulse arterial pressure, number of anti-hypertensive agents [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
• Health-related quality of life (HRQOL) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Physical function as measured by 6 minute walk test [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Serum and peritoneal inflammatory and fibrotic markers: albumin, CRP, IL-6, TNF-a [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Peritoneal membrane transport properties,measured by PET [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Renal and peritoneal solute clearance, 24-hour urine output and ultrafiltration volume [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• left ventricular end-diastolic and systolic volumes, stroke volume and ejection fraction measure by MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Fraility Score [ Time Frame: 1 year ] [ Designated as safety issue: No ]

• Combined outcome of death, non-fatal CV event (stroke, MI, amputation, CHF), and transfer to HD for inadequacy or ultrafiltration failure [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
• Volume measures: bio-impedance (RXc graph, vector length, impedance ratio, phase angle, ECW:TBW ratio), weight, N-BNP, mean and pulse arterial pressure, number of anti-hypertensive agents [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
• Health-related quality of life (HRQOL) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Physical function as measured by 6 minute walk test [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Serum and peritoneal inflammatory and fibrotic markers: albumin, CRP, IL-6, TNF-a [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Peritoneal membrane transport properties,measured by PET [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Renal and peritoneal solute clearance, 24-hour urine output and ultrafiltration volume [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• left ventricular end-diastolic and systolic volumes, stroke volume and ejection fraction measure by MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]

The main purpose of this study is to compare the effects of using bio-impedance analysis to guide management of fluid status versus routine clinical care on heart structure. In addition, Vitamin D is being assessed to determine its effect on heart structure.

Patients on peritoneal dialysis are frequently hypervolemic which is associated with deleterious changes in left ventricular (LV) architecture including increased LV mass. In dialysis patients, increased LV mass is associated with death. Recent randomized trials have demonstrated that increasing small solute clearance is not associated with improved outcomes - hence an increased interest in the management of volume control in ESRD patients. Bioimpedance analysis is inexpensive, safe and easy to use and appears to be more useful than other techniques to assess volume status in dialysis patients. In addition, dialysis patients are vitamin D deficient and this is also associated with an increased LV mass and its inherent complications.

This study will evaluate the use of bioimpedance analysis versus usual care to assess and manage volume status and the use of vitamin D versus placebo in peritoneal dialysis patients and its effect on LV mass as measured by cardiac MRI.

• Drug: Bioimpedance and Vitamin D
  Intervention subjects will undergo BIA assessment monthly for 1 year, and then every 3 months until the end of the planned 3-year study. Protocolized interventions to achieve euvolemia will occur based on the BIA result and they include sodium restriction, addition of diuretics, use of icodextrin, and additional rational changes to the PD prescription.
• Drug: Usual care and placebo
  Usual care (not bioimpedance guided volume management) and Placebo
• Drug: Usual care and Vitamin D
  Usual care (not bioimpedance guided volume management) and Vitamin D
• Device: Bioimpedance and Placebo
  Bioimpedance guided volume management and Placebo

• Experimental: Bioimpedance and Vitamin D
  Intervention: Drug: Bioimpedance and Vitamin D
• Experimental: Usual care and Vitamin D
  Vitamin D3
  Intervention: Drug: Usual care and Vitamin D
• Experimental: Bioimpedance and Placebo
  Intervention: Device: Bioimpedance and Placebo
• Placebo Comparator: Usual Care and Placebo
  Intervention: Drug: Usual care and placebo

Inclusion Criteria:

• Age ≥18 years
• on peritoneal dialysis

Exclusion Criteria:

• Contraindication to MRI including presence of a pacemaker, defibrillator, ferromagnetic cerebral aneurysm clips, cochlear implants or eye prosthesis, neurostimulators, shrapnel in vital locations, surgery within 6 weeks, severe claustrophobia and severe obesity
• Previous amputation
• Life or technique expectancy < 1 year
• Pregnancy
• Peritonitis in previous 3 months
• Currently using more than one extraneal bag per 24-hours
• Known icodextrin allergy
• Currently using non-Baxter PD solutions
• Inability to provide consent
• Allergy to cholecalciferol
• Serum Calcium > 2.55 mmol/L