TY - JOUR A1 - Sharkovska, Yuliya A1 - Reichetzeder, Christoph A1 - Alter, Markus L. A1 - Tsuprykov, Oleg A1 - Bachmann, Sebastian A1 - Secher, Thomas A1 - Klein, Thomas A1 - Hocher, Berthold T1 - Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy JF - Journal of hypertension N2 - Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear. Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes. Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Results: Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well. Conclusion: Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation. KW - diabetic nephropathy KW - DPP-4 inhibitors KW - linagliptin Y1 - 2014 U6 - https://doi.org/10.1097/HJH.0000000000000328 SN - 0263-6352 SN - 1473-5598 VL - 32 IS - 11 SP - 2211 EP - 2223 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Heunisch, Fabian A1 - von Einem, Gina A1 - Alter, Markus L. A1 - Weist, Andreas A1 - Dschietzig, Thomas A1 - Kretschmer, Axel A1 - Hocher, Berthold T1 - Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims: Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. Main methods: We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. Key findings: The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91 +/- 1.23pg/ml versus 0.63 +/- 1.03pg/ml, p<0.001; ET-1/creatinine ratio: 0.14 +/- 0.23 versus 0.09 +/- 0.19, p<0.001). The urinary ET-1 concentrations in patients with CIN decreased significantly more than in patients without CIN (-0.26 +/- 1.42pg/ml vs. -0.79 +/- 1.69pg/ml, p=0.041), whereas the decrease of the urinary ET-1/creatinine ratio was not significantly different (non-CIN patients: -0.05 +/- 0.30; CIN patients: -0.11 +/- 0.21, p=0.223). Urinary ET-1 concentrations as well as the urinary ET-1/creatinine ratio were not associated with clinical events (need for dialysis, rehospitalization or death) during the 90day follow-up after contrast media exposure. However, the urinary ET-1 concentration and the urinary ET-1/creatinine ratio after CM application were higher in those patients who had a decrease of GFR of at least 25% after 90days of follow-up. Significance: In general the ET-1 system in the kidney seems to be down-regulated after contrast media application in patients with moderate CIN risk. Major long-term complications of CIN (need for dialysis, rehospitalization or death) are not associated with the renal ET system. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. KW - Urinary ET-1 KW - Clinical study KW - Radiocontrast media-induced nephropathy KW - Kidney Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2013.12.233 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 440 EP - 445 PB - Elsevier CY - Oxford ER -