Kidney hemodynamic profile and systemic vascular function in adults with type 2 diabetes: Analysis of three clinical trials

Abstract

Aims: Glomerular hyperfiltration plays a key role in the pathophysiology of diabetic kidney disease (DKD). Mechanisms underlying this adverse hemodynamic profile are incompletely understood. We hypothesized that systemic vascular pathology, including endothelial dysfunction and arterial stiffness, relates to glomerular hyperfiltration indicated by filtration fraction (FF). Methods: Baseline data of three trials of overweight adults with type 2 diabetes (TD2, n = 111) with relatively well preserved kidney function were analyzed. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and FF, were assessed with gold-standard clearance techniques. Systemic vascular resistance (SVR), an indicator of endothelial dysfunction, and pulse pressure (PP), a measure of arterial stiffness, were derived from continuous beat-to-beat monitoring. Results: SVR related negatively to GFR (β: −0.382, p < 0.001) and ERPF (β: −0.475, p < 0.001), and positively to FF (β:0.369, p < 0.001). Associations between SVR, ERPF and FF persisted after multivariable adjustments. PP was negatively related to ERPF (β: −0.252, p = 0.008), and positively to FF (β: 0.257, p = 0.006), of which the latter remained significant in multivariable regression. Conclusion: Parameters of systemic vascular pathology, including endothelial dysfunction and arterial stiffness, relate to an adverse kidney hemodynamic profile characterized by glomerular hyperfiltration, which predisposes to the development of DKD.