Kidney Sodium Content in Cardiorenal Patients

NCT ID: NCT04170855

Last Updated: 2025-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-20

Study Completion Date

2026-02-28

Brief Summary

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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

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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.

Conditions

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Cardio-Renal Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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

Group Type OTHER

Furosemide Injection

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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


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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

OTHER

Sponsor Role lead

Responsible Party

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Chris McIntyre

Professor of Medicine, Medical Biophysics and Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher W McIntyre, MD

Role: PRINCIPAL_INVESTIGATOR

Western University

Locations

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

London, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Christopher W McIntyre, MD

Role: CONTACT

519.685.8500 ext. 58502

Fabio Salerno, MD

Role: CONTACT

Facility Contacts

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Justin Dorie, RPN

Role: primary

519-685-8500 ext. 56370

References

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Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007 Sep;93(9):1137-46. doi: 10.1136/hrt.2003.025270.

Reference Type BACKGROUND
PMID: 17699180 (View on PubMed)

Chioncel O, Mebazaa A, Harjola VP, Coats AJ, Piepoli MF, Crespo-Leiro MG, Laroche C, Seferovic PM, Anker SD, Ferrari R, Ruschitzka F, Lopez-Fernandez S, Miani D, Filippatos G, Maggioni AP; ESC Heart Failure Long-Term Registry Investigators. Clinical phenotypes and outcome of patients hospitalized for acute heart failure: the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2017 Oct;19(10):1242-1254. doi: 10.1002/ejhf.890. Epub 2017 Apr 30.

Reference Type BACKGROUND
PMID: 28463462 (View on PubMed)

McCullough PA, Kellum JA, Haase M, Muller C, Damman K, Murray PT, Cruz D, House AA, Schmidt-Ott KM, Vescovo G, Bagshaw SM, Hoste EA, Briguori C, Braam B, Chawla LS, Costanzo MR, Tumlin JA, Herzog CA, Mehta RL, Rabb H, Shaw AD, Singbartl K, Ronco C. Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013;182:82-98. doi: 10.1159/000349966. Epub 2013 May 13.

Reference Type BACKGROUND
PMID: 23689657 (View on PubMed)

Clark AL, Kalra PR, Petrie MC, Mark PB, Tomlinson LA, Tomson CR. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-910. doi: 10.1136/heartjnl-2018-314158.

Reference Type BACKGROUND
PMID: 31118203 (View on PubMed)

Jamison RL. The renal concentrating mechanism: micropuncture studies of the renal medulla. Fed Proc. 1983 May 15;42(8):2392-7.

Reference Type BACKGROUND
PMID: 6341087 (View on PubMed)

Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD003838. doi: 10.1002/14651858.CD003838.pub3.

Reference Type BACKGROUND
PMID: 22336795 (View on PubMed)

Maril N, Rosen Y, Reynolds GH, Ivanishev A, Ngo L, Lenkinski RE. Sodium MRI of the human kidney at 3 Tesla. Magn Reson Med. 2006 Dec;56(6):1229-34. doi: 10.1002/mrm.21031.

Reference Type BACKGROUND
PMID: 17089361 (View on PubMed)

Maril N, Margalit R, Mispelter J, Degani H. Sodium magnetic resonance imaging of diuresis: spatial and kinetic response. Magn Reson Med. 2005 Mar;53(3):545-52. doi: 10.1002/mrm.20359.

Reference Type BACKGROUND
PMID: 15723399 (View on PubMed)

Akbari A, Lemoine S, Salerno F, Marcus TL, Duffy T, Scholl TJ, Filler G, House AA, McIntyre CW. Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys. Radiology. 2022 May;303(2):384-389. doi: 10.1148/radiol.211238. Epub 2022 Feb 8.

Reference Type DERIVED
PMID: 35133199 (View on PubMed)

Other Identifiers

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114884

Identifier Type: -

Identifier Source: org_study_id

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