Kidney Sodium Content in Cardiorenal Patients

January 26, 2024 updated by: Chris McIntyre, Lawson Health Research Institute

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Christopher W McIntyre, MD
  • Phone Number: 58502 519.685.8500
  • Email: cmcint48@uwo.ca

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 3N3
        • Recruiting
        • Heart Failure Clinic | St. Joseph's Health Care London
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Furosemide Injection

Patients with diuretic resistance:

The presence of diuretic resistance, defined as having clinical signs of fluid overload despite diuretic therapy (this information is routinely collected at each clinical visit). "Fluid overload" is defined as the presence of at least two of the following clinical features:

  • Peripheral or sacral oedema
  • Jugular venous distension ≥ 7 cm
  • Radiographic pulmonary oedema or pleural effusion
  • Enlarged liver or ascites
  • Pulmonary rales, paroxysmal nocturnal dyspnoea, or orthopnoea
  • Point of Care UltraSound (POCUS) evidence of congestion. Inferior Vena Cava diameter >2.5 cm and/or failure to collapse at least 50% with sharp inspiration
Drug: Furosemide Injection

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through MRI, an average of 60 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through MRI, an average of 60 minutes
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.
Through MRI, an average of 60 minutes
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
Through MRI, an average of 60 minutes
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)
Through one study visit, and average of 3 hours
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
Through one study visit, and average of 3 hours
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)
Through one study visit, and average of 3 hours
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)
Through one study visit, an average of 3 hours
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 %)
Through one study visit, an average of 3 hours
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.
Through one study visit, an average of 3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Christopher W McIntyre, MD, Western University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2020

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

October 21, 2019

First Submitted That Met QC Criteria

November 18, 2019

First Posted (Actual)

November 20, 2019

Study Record Updates

Last Update Posted (Estimated)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 26, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 114884

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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