@misc{HocherReichetzederAlter2012,
  author    = {Hocher, Berthold and Reichetzeder, Christoph and Alter, Markus L.},
  title     = {Renal and cardiac effects of DPP-4 inhibitors - from preclinical development to clinical research},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  volume    = {36},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  number    = {1},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000339028},
  pages     = {65 -- 84},
  year      = {2012},
  abstract  = {Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.},
  language  = {en}
}
@misc{vonWebskyReichetzederHocher2014,
  author    = {von Websky, Karoline and Reichetzeder, Christoph and Hocher, Berthold},
  title     = {Physiology and pathophysiology of incretins in the kidney},
  series = {Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers},
  volume    = {23},
  journal   = {Current opinion in nephrology and hypertension : reviews of all advances, evaluations of key references, comprehensive listing of papers},
  number    = {1},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {1062-4821},
  doi       = {10.1097/01.mnh.0000437542.77175.a0},
  pages     = {54 -- 60},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}