Sodium Deposition in Soft Tissues of Patients with Kidney Disease

Evaluation of Sodium Deposition in Soft Tissues of Patients with Kidney Disease and Its Association with Patient Symptomatology

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.

Inclusion Criteria:

• Age greater than or equal to 6 years
• For patients on maintenance hemodialysis or peritoneal dialysis: more than 3 months duration of therapy
• For patients with CKD stage 1-5: CKD stage 1-5 and no indications to start dialysis
• For heart failure patients: with or without renal dysfunction
• For healthy controls: lack of kidney disease, heart failure, liver cirrhosis, and peripheral edema

For subsequent visits (must meet 1 of the below indicators):

• Change in dialysis prescription
• Change in renal replacement therapy modality
• Change in medication
• Parathyroidectomy
• Intervention added to or removed from dialysis (i.e. such as but not limited exercise, cooling, and ischemic preconditioning)

Exclusion Criteria:

• Pregnant, breastfeeding or intending pregnancy
• Unable to give consent or understand written information
• Contraindication to MRI study