Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)

Tyrosine kinases-inhibitors targeting vascular endothelial growth factor (VEGF)-receptors (RTKIs) are increasingly used in oncology in several metastatic tumor types. These agents are featured by toxicities including hypertension. According to a new insight, sodium in response to a high dietary sodium intake, is accumulated in a hyperosmolar way in the interstitial compartment. In response to this high sodium concentration cells of the mononuclear phagocytic system (MPS) are activated resulting in an increased production of VEGF-C, activation of VEGF type 3 receptors and formation of a lymphatic capillary network, involved in clearance of interstitial sodium. Blockade of stimulation of VEGF-C receptors or depletion of MPS cells in rodents has been associated with salt-sensitive hypertension.

Sunitinib is an orally-active, multitarget RTKI mainly used for the treatment of patients with metastatic renal cancer and imatinib-resistant gastrointestinal stromal tumors. Sunitinib blocks all three VEGF receptors subtypes, including VEGF-receptor type 3.

The investigators hypothesize that treatment of patients with sunitinib is associated with tissue sodium accumulation and this accumulation contributes to the rise in blood pressure. Tissue sodium is measured by using a newly developed 23Na magnetic resonance-imaging (MRI) technique which allows a non-invasive and contrast agent-free sodium content measurement in the muscle and skin of the lower leg.

Inclusion criteria

• Age men > 18 years
• Life-expectation > 3 months
• Stable weight
• Blood pressure below 140/90 mmHg at baseline
• Estimated glomerular filtration rate > 45 ml/min/1.73m2
• Willingness to give written informed consent

Exclusion criteria

• Heart failure
• Liver disease with ascites
• Nephrotic syndrome
• Gastrointestinal complaints, preventing normal daily food intake or diarrhea
• Any form of diabetes mellitus
• Known autoimmune diseases
• Acute or chronic infection
• Alcohol or substance abuse