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Sodium (Na+) hemostasis is abnormal in CKD patients, and this element can be deposited in the skin, muscle, and skeleton - to cope with long term sodium loading. It is known that sodium stored in this non-osmotically active way, is profoundly inflammatory. Furthermore, inflammation has been associated with several uremic symptoms. The investigators will use novel Na+ MRI imaging to examine the Na+ deposition in the skin, muscle, and skeleton of five groups:1) chronic in-center hemodialysis patients, 2) chronic peritoneal dialysis patients, 3) adult and paediatric patients with CKD stage 1-5 and 4) heart failure patients with and without renal dysfunction 5) sex and age-matched healthy adult and paediatric controls. Additionally, they will investigate the association between sodium deposition in these tissues with uremic symptomatology and biochemical markers of metabolism.
Kidneys have a key role in sodium hemostasis through their excretory function. In patients with chronic kidney disease (CKD), kidney function is impaired; thus, suggesting that sodium handling is abnormal in this setting with long-term sodium loading (from oral intake) and lack of adequate urinary excretion. Yet, sodium concentration needs to stay relatively constant to prevent fatal intra-cellular accumulation, which would result in cell injury and death. In hemodialysis patients, at least a part of this extra sodium is non-osmotically active and deposited in the skin, muscle, and skeleton.
Furthermore, it has become increasingly recognized that sodium (once accumulated in tissues) is directly pro-inflammatory, affecting the innate immune system by regulating the activity of macrophages in skin. This linkage between sodium and inflammation indicates a potential link between sodium deposition and uremic symptoms experienced by patients.
There have been no studies to date examining the sodium deposition in the skin, muscle, and skeleton of patients with different kidney function and renal replacement therapy.
This is a pilot study involving a single center recruiting patients from the prevalent maintenance hemodialysis, peritoneal dialysis , CKD stage 1-5, and heart failure populations of London, Ontario, compared to healthy controls. Once recruited, participants will undergo one study visit with the potential of up to two follow-up visits (on a non-dialysis day for hemodialysis patients). Participants will be followed for up to two years after the first study visit. Each session will include symptom questionnaires, the five times sit to stand and 60-second chair stand test (excluding all children), blood pressure and heart rate measurements, blood work (excluding healthy children and adolescents), urine sampling (excluding those on dialysis), an echocardiogram (excluding healthy controls), and an MRI scan of the lower leg detecting sodium content.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic hemodialysis patients | Patients on standard in-centre 3 times a week hemodialysis |
| |
| Peritoneal dialysis patients | Patients on peritoneal dialysis |
| |
| Adult and paediatric patients with CKD stage 1-5 | Patients with chronic kidney disease stage 1-5 (not dialysis dependent) |
| |
| Healthy adult and paediatric controls | Subjects without kidney disease |
| |
| Heart failure patients with and without renal dysfunction | Heart failure patients (atrial fibrillation etc ...) with and without renal dysfunction |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Measuring sodium content | Other | Sodium MRI measurement of sodium content in the tissues of all participants |
|
| Measure | Description | Time Frame |
|---|---|---|
| Na content in the skin, muscle and skeleton of five cohorts | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Inflammatory Marker: CRP levels | 2 years | |
| Uremic symptom scores among the different groups | 2 years | |
| Liver function markers |
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Inclusion Criteria:
For subsequent visits (must meet 1 of the below indicators):
Exclusion Criteria:
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We will recruit up to 400 participants; approximately 125 dialysis patients including 50 children/adolescents on dialysis, 200 patients with various stages of chronic kidney disease including heart failure patients and approximately 25 children/adolescents with chronic kidney disease, and 75 individuals with no kidney disease including approximately 25 healthy children/adolescents.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christopher W McIntyre, PhD, MD | Contact | 519-685-8500 | 58502 | christopher.mcintyre@lhsc.on.ca |
| Alireza Akbari, PhD | Contact | aakbari@uwo.ca |
| Name | Affiliation | Role |
|---|---|---|
| Christopher W McIntyre, PhD, MD | Western University, Canada | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LHSC Regional Renal Care Program | Recruiting | London | Ontario | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34784242 | Derived | Lemoine S, Salerno FR, Akbari A, McKelvie RS, McIntyre CW. Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target? Circ Cardiovasc Imaging. 2021 Nov;14(11):e012910. doi: 10.1161/CIRCIMAGING.121.012910. Epub 2021 Nov 16. |
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We will measure complete blood count, urea and electrolytes, magnesium, calcium, phosphate, liver function tests, clotting markers, cardiac biomarkers (Troponin T), 25-hydroxyVitamin D and 1,25-dihydroxyVitamin D, CRP, glucose, intact PTH, creatinine, cystatin C, and lactate.
A portion of this blood sample will be sent to the laboratory on-site and the remaining portion will be for processed on-site and stored in the Kidney Clinical Research Unit, LHSC until the end of the study when endotoxin and uremic toxin measurement will be performed.
| 2 years |
| Liver damage markers (liver enzymes) | 2 years |
| cardiac markers (troponin) | 2 years |
| bone markers (ALP, vitamin D levels) | 2 years |
| Uremic toxin levels | 3-4 years |
| Endotoxin levels | 5 years |