@article{HeunischvonEinemAlteretal.2014, author = {Heunisch, Fabian and von Einem, Gina and Alter, Markus L. and Weist, Andreas and Dschietzig, Thomas and Kretschmer, Axel and Hocher, Berthold}, title = {Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function}, series = {Life sciences : molecular, cellular and functional basis of therapy}, volume = {118}, journal = {Life sciences : molecular, cellular and functional basis of therapy}, number = {2}, publisher = {Elsevier}, address = {Oxford}, issn = {0024-3205}, doi = {10.1016/j.lfs.2013.12.233}, pages = {440 -- 445}, year = {2014}, abstract = {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.}, language = {en} } @article{HuberTreszlReibisetal.2013, author = {Huber, Matthias and Treszl, Andras and Reibis, Rona Katharina and Teichmann, Christopher and Zergibel, Irina and Bolbrinker, Juliane and Scholze, Juergen and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold}, title = {Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines}, series = {European journal of internal medicine : official journal of the European Federation of Internal Medicine}, volume = {24}, journal = {European journal of internal medicine : official journal of the European Federation of Internal Medicine}, number = {7}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0953-6205}, doi = {10.1016/j.ejim.2013.03.015}, pages = {650 -- 655}, year = {2013}, abstract = {Background: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients. Methods: Patients (n = 605, mean age 56.2 +/- 9.4 years, 82.3\% male) with arterial hypertension and cardiac ejection fraction (EF) >= 40\% were studied. Cardiac parameters were assessed by echocardiography. Results: The cohort comprised subjects with coronary heart disease (73.1\%) and myocardial infarction (48.1\%) with a mean EF of 63.7 +/- 8.9\%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4 mm Hg, 95\% confidence interval (CI): 0.3 to 4.5 mm Hg, p = 0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8\% (CI: 0.45 to 3.14\%) in carriers versus non-carriers (p = 0.009). Conclusion: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.}, language = {en} }