Adolescents and young adults with youth-onset type 2 diabetes (T2D) are disproportionally impacted by hyperuricemia compared to non-diabetic peers and youth with type 1 diabetes (T1D). In fact, 50% of males with youth-onset T2D have serum uric acid (SUA) greater than 6.8 mg/dl. The investigators also recently demonstrated that higher SUA conferred greater odds of developing hypertension and diabetic kidney disease (DKD) in youth with T2D over 7 years follow-up. Elevated SUA is thought to lead to cardiovascular disease (CVD) and DKD by inflammation, mitochondrial dysfunction and deleterious effects on nephron mass. While there are studies demonstrating beneficial effects of uric acid (UA) lowering on vascular health in the general population, there are no studies in youth-onset T2D. Youth-onset T2D carries a greater risk of DKD and CVD compared to adult-onset T2D and T1D. Accordingly, a clinical trial evaluating UA lowering therapies is needed in youth-onset T2D. Krystexxa (pegloticase), a uricase, effectively lowers SUA and therefore holds promise as a novel therapy to impede the development of CVD and DKD in youth-onset T2D. This proposal describes a pilot and feasibility trial evaluating the effect of UA lowering by pegloticase on markers of CVD and DKD in ten (n=10) youth aged 18-25 with youth-onset T2D (diagnosed \<21 years of age) over 7 days. The overarching hypothesis is that pegloticase improves marker of cardiorenal health by lowering UA.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
One time dosing of pegloticase will be administered. Participants will receive an infusion of pegloticase over two hours in the outpatient clinical and translational research center (CTRC) at Children's Hospital Colorado, and will be monitored after infusion.
Children's Hospital Colorado
Aurora, Colorado, United States
Systolic Blood Pressure
Systolic blood pressure measured by sphygmomanometer
Time frame: Baseline and 1 week post treatment
Diastolic Blood Pressure
Diastolic blood pressure measured by sphygmomanometer
Time frame: Baseline and 1 week post treatment
Mean Arterial Pressure
Mean arterial pressure measured by sphygmomanometer
Time frame: Baseline and 1 week post treatment
Pulse Wave Velocity (PWV)
Measured by Aortic MRI renal MRI (4D Flow)
Time frame: Baseline and 1 week post treatment
Wall Shear Stress (WSS)
Measured by Aortic MRI renal MRI (4D Flow)
Time frame: Baseline and 1 week post treatment
Renal Blood Flow
Measured by 4D Flow renal MRI
Time frame: Baseline and 1 week post treatment
Glomerular Filtration Rate
Measured by Iohexol Clearance in Plasma
Time frame: Baseline and 1 week post treatment
Urine Albumin-creatinine Ratio
Measured by albumin and creatinine concentrations in urine
Time frame: Baseline and 1 week post treatment
Serum Uric Acid (sUA)
Measured by baseline sUA compared to sUA one week later
Time frame: Baseline and 1 week post treatment
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