Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus. Issue 8 (20th January 2016)

• Record Type: Journal Article
• Authors: Lytvyn, Y.; Škrtić, M.; Yang, G. K.; Lai, V.; Scholey, J. W.; Yip, P. M.; Perkins, B. A.; Cherney, D. Z. I.
• Is Part Of: Diabetic medicine. Volume 33:Issue 8(2016:Aug.)
• Page Start: 1102
• Page End: 1111
• Publication Date: 2016-01-20
• Subjects: Diabetes -- Periodicals; 616.462
• DOI: 10.1111/dme.13051
• Languages: English
• ISSNs: 0742-3071

Abstract

Abstract: Aims: Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. Methods: PUA, GFR (inulin) and effective renal plasma flow (ERPF; para‐aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent ( R A ) and efferent ( R E ) arteriolar resistances, glomerular hydrostatic pressure ( P GLO ) and filtration pressure (Δ P F ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. Results: In patients with Type 1 diabetes, higher PUA correlated with lower P GLO ( P = 0.002) and Δ P F ( P = 0.0007), with higher R A ( P = 0.001), but not with R E ( P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR ( P = 0.0007), ERPF ( P = 0.008), RBF ( P = 0.047) and higher RVR ( P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. Conclusions: The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated R A . PUA‐mediated R A may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation. What's new?: For the first time in human data, we show that the association of higher plasma uric acid with lower GFR and renal plasma flow in patients with Type 1 diabetes may be on the basis of increased afferent renal arteriolar resistance. This association may be due to increased tone or thickening of the afferent renal arteriole, leading to renal injury by causing ischaemia to the renal microcirculation. Uric acid‐lowering therapies in patients with Type 1 diabetes may lead to renal protection by avoiding renal ischaemia and the associated decline in renal function—an effect that is being studied in ongoing renal protection trials.