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Physiology and pathophysiology of incretins in the kidney

  • Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species.Purpose of reviewIncretin-based therapy with glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is considered a promising therapeutic option for type 2 diabetes mellitus. Cumulative evidence, mainly from preclinical animal studies, reveals that incretin-based therapies also may elicit beneficial effects on kidney function. This review gives an overview of the physiology, pathophysiology, and pharmacology of the renal incretin system.Recent findingsActivation of GLP-1R in the kidney leads to diuretic and natriuretic effects, possibly through direct actions on renal tubular cells and sodium transporters. Moreover, there is evidence that incretin-based therapy reduces albuminuria, glomerulosclerosis, oxidative stress, and fibrosis in the kidney, partially through GLP-1R-independent pathways. Molecular mechanisms by which incretins exert their renal effects are understood incompletely, thus further studies are needed.SummaryThe GLP-1R and DPP-4 are expressed in the kidney in various species. The kidney plays an important role in the excretion of incretin metabolites and most GLP-1R agonists and DPP-4 inhibitors, thus special attention is required when applying incretin-based therapy in renal impairment. Preclinical observations suggest direct renoprotective effects of incretin-based therapies in the setting of hypertension and other disorders of sodium retention, as well as in diabetic and nondiabetic nephropathy. Clinical studies are needed in order to confirm translational relevance from preclinical findings for treatment options of renal diseases.show moreshow less

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Metadaten
Author:Karoline von Websky, Christoph ReichetzederORCiDGND, Berthold HocherGND
DOI:https://doi.org/10.1097/01.mnh.0000437542.77175.a0
ISSN:1062-4821 (print)
ISSN:1473-6543 (online)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24257158
Parent Title (English):Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers
Publisher:Lippincott Williams & Wilkins
Place of publication:Philadelphia
Document Type:Review
Language:English
Year of first Publication:2014
Year of Completion:2014
Release Date:2017/03/27
Tag:DDP-4 inhibition; GLP-1 receptor; diabetes; diabetic nephropathy; hypertension; incretins; kidney; renal impairment
Volume:23
Issue:1
Pagenumber:7
First Page:54
Last Page:60
Funder:Boehringer Ingelheim
Organizational units:Humanwissenschaftliche Fakultät / Institut für Sportmedizin und Prävention
Peer Review:Referiert