Renal Hemodynamics, Energetics and Insulin Resistance: A Follow-up Study

Glomerular Filtration Rate

Glomerular filtration rate measured by iohexol clearance

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

Effective Renal Plasma Flow (ERPF)

Effective renal plasma flow measured by PAH clearance

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

Renal Oxygen Availability

BOLD-MRI uses the specific paramagnetic properties of deoxyhemoglobin to assess renal tissue oxygenation. Its outcome measure is the so-called R2\* value, which varies inversely with local oxygenation. This apparent relaxation rate R2\* (or decay rate, defined as 1/T2\* and expressed as per second) is measured voxel by voxel in each kidney by BOLD-MRI. The R2\* value of each voxel is influenced by microscopic inhomogeneities in the static magnetic field, largely due to the effect of deoxyhemoglobin. As such, the decay rate R2\* in a voxel will be enhanced when the local deoxyhemoglobin concentration is increased. Hence, assuming that blood pO2 is in equilibrium with tissue pO2, low R2\* values indicate high tissue oxygenation, while high R2\* values indicate low tissue oxygenation.

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

Renal Perfusion

Arterial spin labeling (ASL) uses magnetically labeled arterial blood water as an endogenous tracer to assess renal perfusion. Its outcome measure is renal blood flow (RBF), expressed in mL/min/100 g of tissue. In ASL, inflowing arterial blood is magnetically tagged by inverting the longitudinal magnetization of water protons proximal to the imaging plane. After a defined post-labeling delay allowing labeled blood to flow into the tissue, a labeled image is acquired and subtracted from a control image obtained without labeling. The resulting difference signal, measured voxel by voxel in each kidney, is proportional to the labeled blood water delivered during the delay. As such, the difference signal in a voxel will be enhanced when local blood delivery is increased. Hence, after quantification using tissue and blood relaxation parameters, high perfusion values indicate high renal blood flow, while low perfusion values indicate reduced renal blood flow.

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

C-11 Acetate Tracer Uptake

C-11 Acetate tracer uptake measured by PET Scan (K1)

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening

Renal Oxidative Metabolism

Positron emission tomography (PET) with C-11 acetate is used to assess renal oxidative metabolism. Its outcome measure is the cortical clearance rate constant k2, expressed per minute (min\^-1). Following intravenous injection, C-11 acetate is taken up by renal tissue and converted to acetyl-CoA, which enters the tricarboxylic acid (TCA) cycle and is oxidized to C-11 CO2. The washout of C-11 activity from the tissue, modeled region by region in the renal cortex, reflects the rate of this oxidative process. The clearance rate constant k2, derived from kinetic modeling of the tissue time-activity curve, will be enhanced when oxidative metabolism and TCA cycle flux are increased. Hence, assuming tracer washout is in proportion to mitochondrial oxidation, high cortical k2 values indicate high renal oxidative metabolism, while low cortical k2 values indicate reduced renal oxidative metabolism.

Time frame: One-time measure collected at a single visit following screening; timing varied by participant, up to 7 months after screening