Fluid Overload Management and Vascular Stiffness in Chronic Kidney Disease Patients With Hypertension

This study aims to reduce fluid overload in order to control blood pressure of hypertensive CKD patients using bio-impedance assessment of fluid status and using a diuretic therapy algorithm.

Hypertension is highly prevalent in individuals with chronic kidney disease (CKD). Gradual loss of kidney function is associated with sodium retention. This ultimately leads to fluid overload which has been associated with high blood pressure and heart failure in patients with CKD. In such cases, diuretics are prescribed to reduce fluid overload and thereby control blood pressure. In clinical practice, diuretics are mostly prescribed based on clinical assessment of fluid status (e.g. hypertension, shortness of breath, edema). Less often biomarkers are used like brain natriuretic peptide and bio-impedance spectroscopy. Nevertheless, uncontrolled hypertension is highly prevalent in CKD patients, and leads to accelerated decline in kidney function as well as to cardiovascular disease. Bio-impedance spectroscopy is an accurate tool to assess fluid overload in CKD patients. Accurate assessment of fluid overload and appropriate prescription of diuretics are two pivotal factors to control blood pressure ultimately leading to preservation of kidney function in patients with CKD and decreased cardiovascular risk. Fluid overload in CKD is well documented, however, there are no randomized controlled trials demonstrating that strict fluid overload control in CKD patients improves blood pressure and outcome. Therefore, this study aims to reduce fluid overload in order to control blood pressure of hypertensive CKD patients using bio-impedance assessment of fluid status and using a diuretic therapy algorithm. First, fluid status will be assessed in all study participants using bio-impedance spectroscopy. Second, the study participants will be divided into two groups; the control group which will initially receive standard conventional therapy (no intervention) for 6 months. In the intervention group, the treatment regimen will be adjusted using bio-impedance spectroscopy and a treatment algorithm for diuretic therapy. Medications will be adjusted for 3 months and patients will be followed up for another 3 months. After 6 months, the control group will be subjected to the fluid overload management strategy. The primary outcomes of the current study are improvement in, a) fluid status towards normovolemia, and b) blood pressure toward normotension. Secondary outcome is improvement in vascular health as assessed by pulse wave velocity and augmentation index. Altogether, an optimized fluid status via a fluid management plan will provide better control of fluid overload, blood pressure, and improvement in vascular health in CKD patients.

Eligibility Criteria:
Inclusion Criteria:

* Adult (\>18 years old) outpatient with uncontrolled hypertension; defined as, AMBP ≥ 130/80 mmHg despite treatment
* With an estimated glomerular filtration rate (eGFR) of 15-45 ml/min/1.73 m2.
* Fluid overload of more than 5% of estimated normal ECFV, as assessed by Bio-impedance spectroscopy (we are using the Body Composition Monitor, a validated device marketed by Fresenius, Canada).

Exclusion Criteria:

* Pregnancy or lactation
* Declined informed consent
* Patients with cognitive dysfunction
* Surgery within six weeks of the study
* Patients with heart failure, atrial fibrillation, stroke, nephrotic syndrome and active auto-immune disease
* Patients with severe life-limiting comorbidities like cancer
* Patients with amputated limbs (despite the fact that the BCM device can be used if people have a unilateral amputation, the home devices measure via 2 legs).