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NCT Number: NCT04170855

Kidney Sodium Content in Cardiorenal Patients

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Heart Failure Clinic | St. Joseph's Health Care London

London, Ontario, N6A 3N3, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Furosemide Injection

Drug

We will measure kidney sodium content in patient with cardiorenal syndrome. we will inject within the week of this first measurement furosemide only in patient who will be resistant to diuretics (Based on these parameters, diuretic response will be defined as:

  • A reduction in fractional spot urinary sodium
  • An increase in urinary volume
  • A >1 kg reduction in body weight within 24 hours from diuretic administration (extrapolation of guidance on management of acute HF) and we will do another measurement of kidney sodium content after furosemide injection.

Primary outcomes

  1. Medullary sodium concentration

    Time frame: Through MRI, an average of 60 minutes

    To demonstrate a statistically significant difference in medullary sodium concentration of at least 100 mmol/L between patients with chronic cardiorenal syndrome who are responsive versus patients who are resistant to their current diuretic therapy.

Secondary outcomes

  1. Corticomedullary sodium gradient

    Time frame: Through MRI, an average of 60 minutes

    To demonstrate a difference in corticomedullary sodium gradient between patients with chronic cardiorenal syndrome who are responsive versus patients who are resistant to their current diuretic therapy.

  2. Change in medullary sodium concentration

    Time frame: Through MRI, an average of 60 minutes

    To demonstrate a change in medullary sodium concentration compared to baseline in patients with chronic cardiorenal syndrome and diuretic resistance who show a clinical response to an additional diuretic dose, assessed by the lost of weight.

  3. Change in corticomedullary sodium gradient

    Time frame: Through MRI, an average of 60 minutes

    To demonstrate a change in corticomedullary sodium gradient compared to baseline in patients with chronic cardiorenal syndrome and diuretic resistance who show a clinical response to an additional diuretic dose

  4. Correlation between kidney sodium content and renal function

    Time frame: Through one study visit, and average of 3 hours

    To investigate the correlation between kidney sodium content and renal function assessed by GFR measurement (mL/min/1.73m2)

  5. Correlation between kidney sodium content and biological cardiac biomarker

    Time frame: Through one study visit, and average of 3 hours

    To investigate the correlation between kidney sodium content and cardiac biomarkers assessed by NT-ProBNP

  6. Correlation between kidney sodium content and inflammation

    Time frame: Through one study visit, and average of 3 hours

    To investigate the correlation between kidney sodium content and inflammation biomarkers assessed by CRP (mg/dL)

  7. Correlation between kidney sodium content and NYHA

    Time frame: Through one study visit, an average of 3 hours

    To investigate the correlation between kidney sodium content and NYHA class (no unit, scale from 0 to 4)

  8. Correlation between kidney sodium content and echocardiography

    Time frame: Through one study visit, an average of 3 hours

    To investigate the correlation between kidney sodium content and left ejection fraction (in %)

  9. Correlation between kidney sodium content and Bioimpedance spectroscopy

    Time frame: Through one study visit, an average of 3 hours

    To investigate the correlation between kidney sodium content and extra cellular volume content (in liters) measured by bioimpedance spectroscopy.

Sponsors and collaborators

Lead sponsor

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Other

Registry information

Official study title

Evaluation of Kidney Medullary Sodium Content Using 23Na MRI to Understand and Predict Diuretic Resistance

Important dates

Study start
2020
Primary completion
2026
Study completion
2027
First posted
Nov 20, 2019
Registry last updated
May 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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