Clinical trial NCT04170855: Kidney Sodium Content in Cardiorenal Patients
Official title: Evaluation of Kidney Medullary Sodium Content Using 23Na MRI to Understand and Predict Diuretic Resistance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardio-Renal Syndrome
Keywords: kidney sodium content
Sodium MRI
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2019-11-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Diuretic therapy is the cornerstone of the management of fluid overload in heart failure. Resistance to diuretic therapy is the most common reason for treatment failure in patients affected by the combination of heart failure and kidney disease. Currently, there is no way of predicting whether heart failure patients will develop resistance to diuretic therapy and what dose of diuretic is necessary to overcome diuretic resistance. Answering these questions would allow doctors to be able to prescribe an accurate dose of diuretic therapy to prevent diuretic resistance and potential side effects of an excessive diuretic dose.

With magnetic resonance imaging, it is possible to measure the kidney sodium (salt) content and observe the diuretic response in patients with heart failure and kidney disease. The investigators speculate that measuring kidney sodium content will allow to predict diuretic response in these patients.

The aim of this study is to compare the kidney sodium content in patients with chronic cardiorenal syndrome with and without diuretic resistance. Secondly, in a sample of patients with diagnosed diuretic resistance,the aim will be to observe the changes in kidney sodium content induced by an additional dose of diuretic therapy and to observe whether these changes are associated with a response to diuretic therapy.

Detailed description: This is a prospective, interventional, pilot study involving patients recruited from the Heart Failure outpatient clinic at St. Joseph's Hospital in London, Ontario. Depending on scanner availability, the study visits may also take place at Robarts Research Institute, University of Western Ontario. All eligible patients who consent to take part in the study will undergo one study visit. During this visit, all study participants will undergo a combined proton (1H) and 23Na MRI scan of their kidneys to measure kidney sodium content. Prior to the scan, all participants will be asked to complete a questionnaire, will have their fluid volume measured using bioimpedance spectroscopy, will have their heart failure classified using the NYHA system, will have their weight taken using a clinical scale, and will have their sitting blood pressure and heart rate measured three times consecutively using a standard automatic blood pressure monitor. In addition to this, all participants will undergo a research focused echocardiogram, provide a spot urine sample and have blood work collected. All participants will be responsible to complete a 24-hour urine volume test the day before the study visit and bring the special container to the team on the visit day.

Study participants who meet the criteria for diuretic resistance will undergo a second study visit within one week of the first one. During this visit, participants will receive an additional intravenous dose of diuretic (furosemide) and they will subsequently undergo a second proton and 23Na MRI scan of their kidneys. Prior to the scan participants will undergo the same study procedures as in visit one excluding the questionnaire. In addition to this, participants will be responsible to record their weight at home the morning before the visit and bring their weight to the study team. After the scan, all participants will have their blood pressure, heart, rate, and weight measured again, and will be asked to complete a 24-hour urine collection. Furthermore, participants will be asked to take their weight using a home scale the morning after the scan and a member of the research team will phone the participants to collect this information.

Eligibility criteria: Inclusion Criteria for Visit 1

* Clinico-pathological diagnosis of heart failure
* Age ≥ 18 years
* Estimated GFR ≥ 15 mL/min/1.73m2
* Receiving loop diuretics for at least a week at ≥ 40 mg/day (furosemide) or 2 mg/day (bumetanide), either orally or intravenously
* Willing and able to provide consent

Inclusion Criteria for Visit 2 · Patients from visit 1 with diuretic resistance

Exclusion Criteria for Visit 1 Direct contraindications to MR scanning (implanted materials etc.)

* Additional diuretic types other than spironolactone/epleronone/metolazone/finerenone
* Liver disease with hepato-renal syndrome
* Pregnant, breastfeeding or intending pregnancy
* Kidney malformation leading to chronic kidney disease (for example polycystic kidney)
* Unable to provide consent

Exclusion criteria for Visit 2

· Hypokalemia (serum potassium \<3.5 mmol/l)

Primary outcomes:
measure: Medullary sodium concentration
timeFrame: Through MRI, an average of 60 minutes
Secondary outcomes:
measure: Corticomedullary sodium gradient
timeFrame: Through MRI, an average of 60 minutes
measure: Change in medullary sodium concentration
timeFrame: Through MRI, an average of 60 minutes
measure: Change in corticomedullary sodium gradient
timeFrame: Through MRI, an average of 60 minutes
measure: Correlation between kidney sodium content and renal function
timeFrame: Through one study visit, and average of 3 hours
measure: Correlation between kidney sodium content and biological cardiac biomarker
timeFrame: Through one study visit, and average of 3 hours
measure: Correlation between kidney sodium content and inflammation
timeFrame: Through one study visit, and average of 3 hours
measure: Correlation between kidney sodium content and NYHA
timeFrame: Through one study visit, an average of 3 hours
measure: Correlation between kidney sodium content and echocardiography
timeFrame: Through one study visit, an average of 3 hours
measure: Correlation between kidney sodium content and Bioimpedance spectroscopy
timeFrame: Through one study visit, an average of 3 hours
Other outcomes:
Locations:
city: London
country: Canada
facility: Heart Failure Clinic | St. Joseph's Health Care London
state: Ontario
Study officials:
affiliation: Western University
name: Christopher W McIntyre, MD
role: PRINCIPAL_INVESTIGATOR
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