The Association Between Uric Acid, Renal Hemodynamics and Arterial Stiffness Over the Natural History of Type 1 Diabetes.

Aims To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. Materials and methods PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean +/- SD age 16.8 +/- 1.9 years), 52 young adults (mean +/- SD age 25.6 +/- 5.5 years) and 66 older adults (mean +/- SD age 65.7 +/- 7.5 years). Results PUA was highest in patients with the longest T1D duration: 197 +/- 44 mu mol/L in adolescents versus 264 +/- 82 mu mol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (beta = -2.12 +/- 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (beta = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. Conclusions The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.