Kidney hemodynamic profile and systemic vascular function in adults with type 2 diabetes: Analysis of three clinical trials
Hesp, Anne C.; Smits, Mark M.; van Bommel, Erik J.M.; Muskiet, Marcel H.A.; Tonneijck, Lennart; Nieuwdorp, Max; Kramer, Mark H.H.; Joles, Jaap A.; Bjornstad, Petter; van Raalte, Daniël H.
(2022) Journal of Diabetes and its Complications, volume 36, issue 3, pp. 1 - 6
(Article)
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
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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.
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Keywords: Arterial stiffness, Diabetes mellitus type 2, Diabetic kidney disease, Endothelial dysfunction, Glomerular hyperfiltration, Kidney hemodynamics, Internal Medicine, Endocrinology, Diabetes and Metabolism, Endocrinology
ISSN: 1056-8727
Publisher: Elsevier Inc.
Note: Funding Information: The RENALIS trial was funded by Boehringer Ingelheim. The funder had no role in the design, the analyses, or the interpretation of the data or drafting of the manuscript. Funding Information: The authors are very grateful for the time and commitment of all participants who volunteered for the trials. In addition, the authors acknowledge the help of the study nurses and assistants who were indispensable in the process of data collection: Ren?e de Meijer, Jeannette Boerop, and Ingrid Knufman (Diabetes Center, Department of Internal Medicine, AUMC, location VUMC). The SAFEGUEARD trial was funded by the Seventh Framework Programme (FP7/2007-2013) of the European commission under grant no. 282521. The funder had no role in the design, the analyses, or the interpretation of the data or drafting of the manuscript. The RENALIS trial was funded by Boehringer Ingelheim. The funder had no role in the design, the analyses, or the interpretation of the data or drafting of the manuscript. The RED trial was funded by AstraZenenca as an invesitgator-initiated study. The funder had no role in the design, the analyses, or the interpretation of the data or drafting of the manuscript. A.C. Hesp: Formal analysis, Visualization, Writing- original draft. M.M. Smits: Investigation, resources, Writing ? Review & Editing. E.J. van Bommel: Investigation, Writing ? Review & Editing. M.H.A. Muskiet: Investigation, Writing ? Review & Editing. L. Tonneijck: Investigation, Writing ? Review & Editing. M. Nieuwdorp: Writing ? Review & Editing. M.H.H. Kramer: Writing ? Review & Editing. J.A. Joles: Writing ? Review & Editing. P. Bjornstad: Supervision, Writing ? Review & Editing. D.H. van Raalte: Supervision, Conceptualisation, Methodology, Funding acquisition, Writing ? Review & Editing. MHAM is a speaker/consultant for AstraZeneca, Eli Lilly & Co. Novo Nordisk, and Sanofi. MN received an unrestricted grant from AstraZeneca and is supported by a ZonMW-VIDI grant 2013 (016.146.327) and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013. PB has acted as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. serves on the advisory board of XORTX. DHR has served as a consultant andreceived honoraria from Boehringer Ingelheim and Lilly, Merck, Novo Nordisk,Sanofi, and AstraZeneca and has received research operating funds from Boehringer Ingelheim and Lilly Diabetes Alliance, AstraZeneca, and NovoNordisk; all honoraria are paid to his employer (Amsterdam University MedicalCenters, location VU University Medical Center). All other authors declare no conflict of interests. Funding Information: MHAM is a speaker/consultant for AstraZeneca, Eli Lilly & Co., Novo Nordisk, and Sanofi. MN received an unrestricted grant from AstraZeneca and is supported by a ZonMW-VIDI grant 2013 ( 016.146.327 ) and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013. PB has acted as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. serves on the advisory board of XORTX. DHR has served as a consultant andreceived honoraria from Boehringer Ingelheim and Lilly, Merck, Novo Nordisk,Sanofi, and AstraZeneca and has received research operating funds from Boehringer Ingelheim and Lilly Diabetes Alliance, AstraZeneca, and NovoNordisk; all honoraria are paid to his employer (Amsterdam University MedicalCenters, location VU University Medical Center). All other authors declare no conflict of interests. Funding Information: The SAFEGUEARD trial was funded by the Seventh Framework Programme (FP7/2007-2013) of the European commission under grant no. 282521 . The funder had no role in the design, the analyses, or the interpretation of the data or drafting of the manuscript. Publisher Copyright: © 2022
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