Kidney Sodium Content in Cardiorenal Patients

Cardio-Renal Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04170855
• Other study ID #: 114884
• Status: Recruiting
• Phase: N/A
• Start date: October 20, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Lawson Health Research Institute
• Contact: Christopher W McIntyre, MD
• Phone: 519.685.8500
• Email: cmcint48[@]uwo.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardio-Renal Syndrome

Intervention

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.

Locations

Country	Name	City	State
Canada	Heart Failure Clinic | St. Joseph's Health Care London	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Medullary sodium concentration	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	Corticomedullary sodium gradient	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
Secondary	Change in medullary sodium concentration	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
Secondary	Change in corticomedullary sodium gradient	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
Secondary	Correlation between kidney sodium content and renal function	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
Secondary	Correlation between kidney sodium content and biological cardiac biomarker	To investigate the correlation between kidney sodium content and cardiac biomarkers assessed by NT-ProBNP	Through one study visit, and average of 3 hours
Secondary	Correlation between kidney sodium content and inflammation	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
Secondary	Correlation between kidney sodium content and NYHA	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
Secondary	Correlation between kidney sodium content and echocardiography	To investigate the correlation between kidney sodium content and left ejection fraction (in %)	Through one study visit, an average of 3 hours
Secondary	Correlation between kidney sodium content and Bioimpedance spectroscopy	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