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      Update on Pathogenesis of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

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          Abstract

          In the existing stages of diabetic kidney disease (DKD), the first stage of DKD is called the preclinical stage, characterized by glomerular hyperfiltration, an abnormally elevated glomerular filtration rate. Glomerular hyperfiltration is an independent risk factor for accelerated deterioration of renal function and progression of nephropathy, which is associated with a high risk for metabolic and cardiovascular disease. It is imperative to understand hyperfiltration and identify potential treatments to delay DKD progress. This paper summarizes the current mechanisms of hyperfiltration in early DKD. We pay close attention to the effect of glucose reabsorption mediated by sodium–glucose cotransporters and renal growth on hyperfiltration in DKD patients, as well as the mechanisms of nitric oxide and adenosine actions on renal afferent arterioles via tubuloglomerular feedback. Furthermore, we also focus on the contribution of the atrial natriuretic peptide, cyclooxygenase, renin–angiotensin–aldosterone system, and endothelin on hyperfiltration. Proposing potential treatments based on these mechanisms may offer new therapeutic opportunities to reduce the renal burden in this population.

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          Most cited references136

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          Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

          Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
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            Dapagliflozin in Patients with Chronic Kidney Disease

            Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.
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              Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials

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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                19 May 2022
                2022
                : 13
                : 872918
                Affiliations
                [1]Department of Nephrology, The Second Affiliated Hospital of Nanchang University , Nanchang, China
                Author notes

                Edited by: Francisco Westermeier, FH Joanneum, Austria

                Reviewed by: Akira Sugawara, Tohoku University, Japan; Tatsuo Shimosawa, International University of Health and Welfare (IUHW), Japan; Sebastián Alarcón, Austral University of Chile, Chile

                *Correspondence: Gaosi Xu, gaosixu@ 123456163.com

                This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.872918
                9161673
                ae81e95d-6685-4f3d-bbaa-4b256be74b00
                Copyright © 2022 Yang and Xu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 February 2022
                : 11 April 2022
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 136, Pages: 11, Words: 4728
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81970583, 82060138
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                diabetic kidney disease,glomerular hyperfiltration,sodium–glucose cotransporter,tubuloglomerular feedback,renal hemodynamics

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