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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2017; 8(5): 172-186
Published online May 15, 2017. doi: 10.4239/wjd.v8.i5.172
Effects of glycaemic management on diabetic kidney disease
Richard J MacIsaac, George Jerums, Elif I Ekinci
Richard J MacIsaac, Department of Endocrinology and Diabetes, St Vincent’s Hospital, Melbourne, Victoria 3065, Australia
Richard J MacIsaac, Department of Medicine, St Vincent´s Hospital, University of Melbourne, Melbourne, Victoria 3065, Australia
George Jerums, Elif I Ekinci, Endocrine Centre, Austin Health, Melbourne, Victoria 3081, Australia
George Jerums, Elif I Ekinci, Department of Medicine at Austin Health, University of Melbourne, Victoria 3081, Australia
Author contributions: MacIsaac RJ drafted this manuscript; all authors equally contributed to this paper with literature review and analysis and critical revision and editing, and final approval of the final version.
Supported by ADS-Sevier Research Grant (to MacIsaac RJ).
Conflict-of-interest statement: Professor MacIsaac RJ has received honoraria and travel support for lectures from Eli lily, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Merck Sharp and Dohme and Norvartis; he has received research grants from Novo Nordisk and Sevier in the past.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Richard J MacIsaac, Professor, BSc(HONS), PhD, MBBS, FRACP, Director, Department of Endocrinology and Diabetes, St Vincent’s Health, PO Box 2900, Fitzroy, Melbourne, Victoria 3065, Australia. r.macisaac@unimelb.edu.au
Telephone: +61-3-92313569 Fax: +61-3-92313590
Received: August 27, 2016
Peer-review started: August 31, 2016
First decision: October 20, 2016
Revised: February 25, 2017
Accepted: March 14, 2017
Article in press: March 17, 2017
Published online: May 15, 2017
Abstract

Hyperglycaemia contributes to the onset and progression of diabetic kidney disease (DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro- or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin’s reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects of newer glucose lowering agents.

Keywords: Diabetic nephropathy, Albuminuria, Glucose control, Glomerular filtration rate, Diabetes, Chronic kidney disease, Empagliflozin, Liraglutide, Semaglutide

Core tip: Tight glucose control has been clearly shown to reduce the incidence of micro- and macroalbuminuria. Evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Furthermore, empagliflozin which is a glucose lowering agent of the sodium glucose like transporter-2 inhibitor class has been shown to have reno-protective effects over and above those expected from its glucose lowering effects alone. Recent clinical trials have also shown that Liraglutide and Semaglutide, injectable glucose lowering agents which are analogues of human glucagon like peptide-1, reduce progression to macroalbuminuria.