@article{FreyHenzeNagletal.2009,
  author    = {Frey, Simone K. and Henze, Andrea and Nagl, Britta and Raila, Jens and Scholze, Alexandra and Tepel, Martin and Schweigert, Florian J. and Zidek, Walter},
  title     = {Effect of renal replacement therapy on retinol-binding protein 4 isoforms},
  issn      = {0009-8981},
  doi       = {10.1016/j.cca.2008.11.008},
  year      = {2009},
  abstract  = {Background: Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms. Methods: We investigated serum levels of RBP4, apo-RBP4, holo-RBP4, RBP4-L, RBP4-LL, retinol and transthyretin (TTR) in 18 hemodialysis (HD) patients, 30 patients after renal transplantation (RTx) and in 35 healthy controls. RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay, apo- and holo-RBP4 by native electrophoresis, retinol by high performance liquid chromatography and RBP4-L and RBP4-LL were analyzed by mass spectrometry. Results: HD and RTx patients had elevated RBP4, apo-RBP4 and RBP4-LL levels compared to controls. RTx patients had elevated amounts of RBP4-L compared to controls and elevated RBP4 and apo-RBP4 levels compared to HD patients. Conclusion: The results demonstrate a strong correlation between kidney function and RBP4 isoforms and provide data for investigating the relation of RBP4 and insulin resistance in these patients.},
  language  = {en}
}
@article{HenzeRailaScholzeetal.2013,
  author    = {Henze, Andrea and Raila, Jens and Scholze, Alexandra and Zidek, Walter and Tepel, Martin and Schweigert, Florian J.},
  title     = {Does N-Acetylcysteine modulate post-translational modifications of transthyretin in hemodialysis patients?},
  series = {Antioxidants \& redox signaling},
  volume    = {19},
  journal   = {Antioxidants \& redox signaling},
  number    = {11},
  publisher = {Liebert},
  address   = {New Rochelle},
  issn      = {1523-0864},
  doi       = {10.1089/ars.2012.5125},
  pages     = {1166 -- 1172},
  year      = {2013},
  abstract  = {It is assumed that effects of the thiol antioxidant N-acetylcysteine (NAC) are mediated by interaction with protein-associated cysteine residues, however, information on protein level in vivo are missing. Therefore, we analyzed NAC-induced modifications of the protein transthyretin (TTR) in plasma of hemodialysis patients in a randomized, placebo-controlled study. TTR was selected due to its low molecular weight and the free cysteine residue in the polypeptide chain, which is known to be extensively modified by formation of mixed disulfides. The intravenous application of NAC during a hemodialysis session resulted in a substantial increase of native TTR from median 15\% (range 8.8\%-30\%) to median 40\% (37-50) and reduction of S-cysteinylated TTR [51\% (44-60) vs. 6.6\% (2.4-10)]. Additionally the pronounced formation of a TTR-NAC adduct was detected. However, all these modifications seemed to be reversible. Additionally, in vitro incubation of plasma with NAC confirmed the in vivo results and indicated that changes in post-translational modification pattern of TTR were a function of NAC concentration. Based on these observations and the essential metabolic and biochemical role of protein-associated cysteine residues we hypothesize that the interaction of NAC with proteins may explain altered protein functions due to modification of cysteine residues. Antioxid. Redox Signal. 19, 1166-1172.},
  language  = {en}
}
@article{TepelArmbrusterGroenetal.2013,
  author    = {Tepel, Martin and Armbruster, Franz Paul and Groen, Hans Juergen and Scholze, Alexandra and Reichetzeder, Christoph and Roth, Heinz J{\"u}rgen and Hocher, Berthold},
  title     = {Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients},
  series = {The journal of clinical endocrinology \& metabolism},
  volume    = {98},
  journal   = {The journal of clinical endocrinology \& metabolism},
  number    = {12},
  publisher = {Endocrine Society},
  address   = {Chevy Chase},
  issn      = {0021-972X},
  doi       = {10.1210/jc.2013-2139},
  pages     = {4744 -- 4751},
  year      = {2013},
  abstract  = {Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity. Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system. Results: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50\%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (chi(2), 14.3; P = 0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels. Conclusions: The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality.},
  language  = {en}
}
@article{HenzeFreyRailaetal.2010,
  author    = {Henze, Andrea and Frey, Simone K. and Raila, Jens and Scholze, Alexandra and Spranger, Joachim and Weickert, Martin O. and Tepel, Martin and Zidek, Walter and Schweigert, Florian J.},
  title     = {Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters},
  issn      = {0006-291X},
  doi       = {10.1016/j.bbrc.2010.01.082},
  year      = {2010},
  abstract  = {Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients.},
  language  = {en}
}
@inproceedings{HocherArmbrusterScholzeetal.2013,
  author    = {Hocher, Berthold and Armbruster, Franz Paul and Scholze, Alexandra and Marckmann, Peter and Reichetzeder, Christoph and Roth, Heinz J{\"u}rgen and Tepel, Martin},
  title     = {Non-oxidized, biological active parathyroid hormone determines motality in hemodialsysis patients},
  series = {Nephrology, dialysis, transplantation},
  volume    = {28},
  booktitle = {Nephrology, dialysis, transplantation},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  pages     = {33 -- 33},
  year      = {2013},
  language  = {en}
}
@inproceedings{HenzeRailaScholzeetal.2013,
  author    = {Henze, Andrea and Raila, Jens and Scholze, Alexandra and Schweigert, Florian J. and Tepel, Martin},
  title     = {Administration of N-Acetylcyteine causes beneficial posttranslationalmodifications of transthyretin in hemodialysis patients},
  series = {Nephrology, dialysis, transplantation},
  volume    = {28},
  booktitle = {Nephrology, dialysis, transplantation},
  number    = {2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  pages     = {164 -- 164},
  year      = {2013},
  language  = {en}
}
@article{ScholzeLiuPedersenetal.2014,
  author    = {Scholze, Alexandra and Liu, Ying and Pedersen, Lise and Xia, Shengqiang and Roth, Heinz J. and Hocher, Berthold and Rasmussen, Lars Melholt and Tepel, Martin},
  title     = {Soluble alpha-Klotho and its relation to kidney function and fibroblast growth factor-23},
  series = {The journal of clinical endocrinology \& metabolism},
  volume    = {99},
  journal   = {The journal of clinical endocrinology \& metabolism},
  number    = {5},
  publisher = {Endocrine Society},
  address   = {Washington},
  issn      = {0021-972X},
  doi       = {10.1210/jc.2013-4171},
  pages     = {E855 -- E861},
  year      = {2014},
  abstract  = {Context: Relations between fibroblast growth factor-23 (FGF-23), soluble alpha-klotho (s-alpha-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-alpha-klotho requires further study. Objectives: Our objectives were to analyze the relation of s-alpha-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-alpha-klotho to cholecalciferol. Patients, Design, and Setting: Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency). Interventions: Interventions included 40 000 IU cholecalciferol or placebo weekly. Main Outcome Measure: S-alpha-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1. Results: For all patients, s-alpha-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-alpha-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-alpha-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-alpha-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-alpha-klotho. Conclusions: CKD patients with s-alpha-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-alpha-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-alpha-klotho concentrations.},
  language  = {en}
}
@inproceedings{ScholzePetersenHocheretal.2014,
  author    = {Scholze, Alexandra and Petersen, Lise and Hocher, Berthold and Rasmussen, Lars M. and Tepel, Martin},
  title     = {Role of fibroblast growth factor-23 and soluble alpha klotho in chronic kidney disease},
  series = {Nephrology, dialysis, transplantation},
  volume    = {29},
  booktitle = {Nephrology, dialysis, transplantation},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  pages     = {120 -- 121},
  year      = {2014},
  language  = {en}
}