Head-to-head comparison of structurally unrelated dipeptidyl peptidase 4 inhibitors in the setting of renal ischemia reperfusion injury

结构无关的二肽基肽酶 4 抑制剂在肾缺血再灌注损伤中的直接比较

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作者:Christoph Reichetzeder, Karoline von Websky, Oleg Tsuprykov, Azadeh Mohagheghi Samarin, Luise Gabriele Falke, Sulistyo Emantoko Dwi Putra, Ahmed Abdallah Hasan, Viktoriia Antonenko, Caterina Curato, Jörg Rippmann, Thomas Klein, Berthold Hocher0

Results

Plasma-active glucagon-like peptide type 1 (GLP-1) increased threefold to fourfold in all DPP4 inhibitor groups 24 h after IRI. Plasma cystatin C, a marker of GFR, peaked 48 h after IRI. Compared with the placebo group, DPP4 inhibition did not reduce increased plasma cystatin C levels. DPP4 inhibitors ameliorated histopathologically assessed tubular damage with varying degrees of drug-specific efficacies. Renal osteopontin expression was uniformly reduced by all DPP4 inhibitors. IRI-related increased renal cytokine expression was not decreased by DPP4 inhibition. Renal DPP4 activity at study end was significantly inhibited in the linagliptin group, but only numerically reduced in the prolonged/dose-adjusted sitagliptin group. Active GLP-1 plasma levels at study end were increased only in the prolonged/dose-adjusted sitagliptin treatment group. Conclusions and implications: In rats with renal IRI, DPP4 inhibition did not alter plasma cystatin C, a marker of glomerular function, but may protect against tubular damage.

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