Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis

Ottawa Hospital Research Institute50 enrolled

Overview

Hypothesis: Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and leptin levels and will reverse dialysis-induced increases in sympathetic activity.

Cardiovascular mortality remains higher among patients treated with peritoneal dialysis as compared to patients treated with hemodialysis. Sympathetic hyperactivity is considered a significant emerging risk factor for cardiovascular mortality among patients with ESRD (End-Stage Renal Disease). Sympathetic activity, via its hemodynamic effects and trophic effects, and in interaction with RAAS (Renin Angiotensin Aldosterone System), does play a major role in cardiac and vascular remodelling, development of LVH and vascular hypertrophy, as well as progression to CHF. Glucose-based dialysate induces hyperinsulinemia and hyperleptinemia. We propose that hyperleptinemia induced by glucose-based peritoneal solution is a significant contributing factor to sympathetic hyperactivity in ESRD patients treated with PD, and could be prevented by non-glucose-based PD solution such as icodextrin-based. Adult patients with ESRD starting PD as their first renal replacement therapy modality will be studied. Patients will be recruited 1-3 weeks prior to starting PD treatment. At baseline, specific studies for microneurography (MSNA), fasting plasma insulin, leptin, catecholamines and brain natriuretic peptide (BNP) will be performed. EKG will be recorded and digitized for further assessment of heart rate variability using power spectral analysis. Extracellular fluid volume status will be assessed by bioelectrical impedance. Central vascular volume will be assessed from inferior vena cava (IVC) by heart ultrasound. Consequently 24-h ambulatory blood pressure monitoring(ABPM)and a 24-h urine collection for urea clearance and creatinine clearance will be done. All participants into the study will receive a PD treatment for 6 weeks with standard glucose-based PD solution Dianeal. The specific studies are repeated at 6 weeks.Then, patients will be randomized to one of the two groups (arms). One group will continue with Dianeal PD solution for another 12 weeks. The other group will receive Dianeal during the day and Extraneal, icodextrin or non-glucose based solution, during the night only, for the next 12 weeks. The specific studies are repeated at 12 weeks after randomization (18 weeks of PD treatment).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

End-stage Renal Disease (ESRD)Kidney Disease

Interventions

DIANEALOTHER

EXTRANEALOTHER

Weeks 1 to 6 (6 weeks): * CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night * CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): * CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of EXTRANEAL during the night * CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and one 8-12-hour dwell of EXTRANEAL during the night

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult (age 18 years and older) * Patients with end-stage renal disease(ESRD)/chronic kidney disease(CKD)stage 5 Exclusion Criteria: * Diabetes Mellitus * Acute coronary syndrome in the past 6 months * Cardiac arrhythmias (2nd and 3rd degree heart block or premature ventricular complexes in Lown classes 4 or 5) * Symptoms suggestive of obstructive or central sleep apnea (with a score of \> 10 on Epworth sleepiness scale) * Patients taking Clonidine * Body mass index (BMI) \> 34 * Patients unable to give consent * Pregnant women * Patients with leg injury involving nerve damage * Patients taking anticoagulant medication * Patients with significant bleeding disorder or liver disorder * Hemoglobin \<1.05 g/dl at the time of initiation of therapy * patients with unilateral or bilateral nephrectomy * Planned kidney transplant in the next 4 months * Life expectancy under 6 months * Oliguria (urine output less than 400 ml per day)

Locations (1)

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Outcomes

Primary Outcomes

Changes in muscle sympathetic nerve activity(MSNA)

Muscle sympathetic nerve activity(MSNA) is measured by microneurography at * baseline (before starting peritoneal dialysis) * 6 weeks of PD * 18 weeks of PD(12 weeks after randomization) MSNA increases on a glucose-based dialysis regimen and may decrease by adding non-glucose-based solution

Time frame: 6 weeks on PD and 18 weeks on PD

Changes in leptin levels

Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen

Time frame: 6 weeks on PD and 18 weeks on PD

Secondary Outcomes

Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM)

Blood pressure will be assessed with 24-hour ABPM at baseline, 6 weeks on PD and 18 weeks after starting peritoneal dilaysis. Summary measures of each day and night period include average systolic and diastolic BP as well as % nocturnal dipping. These summary measures can predict cardiovascular events more accurately than casual BP measures

Time frame: 6 weeks on PD and 18 weeks on PD

Changes in extracellular volume assessed by bioelectrical impedance (BIA)

Bioelectrical impedance directly measures extracellular fluid volume and total body water. The test is based on the ability to detect differences in the conductive properties of a cell by measuring its resistance (impedance) to electrical current. The technique is reliable for tracking sequential changes in extracellular fluid volume.

Time frame: 6 weeks on PD and 18 weeks on PD

Changes in heart rate variability

During the microneurography testing, EKG is recorded. Heart rate and heart rate variability(HRV) will be analyzed from EKG data at baseline, 6 weeks and 18 weeks after starting dialysis.

Data from ClinicalTrials.gov

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