title: Physiology and pathophysiology of incretins in the kidney.
abstract: OBJECTIVE
  Incretin-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.
  
  
  RESULTS
  Activation 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: aInstitute of Nutritional Science, University of Potsdam, Potsdam bCenter for Cardiovascular Research, Charité, Berlin, Germany.
authors.forename: Karoline
authors.initials: K
authors.lastname: von Websky
authors.forename: Christoph
authors.initials: C
authors.lastname: Reichetzeder
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4