Higher plasma uric acid (PUA) levels are associated with lower GFR and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D.
T1D patients (n=49) were studied under eu- and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy controls (HC) were studied under normoglycemic conditions (n=24). PUA, GFR (inulin), effective renal plasma flow (ERPF, paraaminohippurate), BP and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal RAAS) were measured pre- and post-FBX. Arterial stiffness, flow and nitroglycerin mediated dilation (FMD, GMD), urinary nitric oxide (NO) and inflammatory markers were measured pre- and post-FBX. Gomez’s equations were used to estimate afferent (RA) and efferent (RE) arteriolar resistances and glomerular hydrostatic pressure (PGLO).
FBX had a modest systolic BP lowering effect in T1D patients (112±10 to 109±9 mmHg, p=0.049), without impacting arterial stiffness, FMD, GMD or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients, through larger increases in RE, PGLO and interleukin-18, but without impacting the RAAS.
FBX lowered systolic BP and modulated the renal RE responses to hyperglycemia, but without impacting the RAAS or NO, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.
* co-senior authors
- Received February 7, 2017.
- Accepted April 4, 2017.
- © 2017 by the American Diabetes Association.