TY - CHAP A1 - Doyon, Anke A1 - Schmiedchen, Bettina A1 - Bayazit, Aysun A1 - Canpolat, Nur A1 - Duzova, Ali A1 - Kracht, Daniela A1 - Litwin, Mieczyslaw A1 - Niemirska, Anna A1 - Sozeri, Betul A1 - Zeller, Rene A1 - Anarat, Ali A1 - Caliskan, Salim A1 - Mir, Sevgi A1 - Shroff, Rukshana A1 - Melk, Anette A1 - Wühl, Elke A1 - Schweigert, Florian J. A1 - Querfeld, Uwe A1 - Schäfer, Franz T1 - Altered arterial morphology and function in children with CKD Role of mineral-bone disorder T2 - Pediatric nephrology : journal of the International Pediatric Nephrology Association Y1 - 2012 SN - 0931-041X VL - 27 IS - 9 SP - 1606 EP - 1607 PB - Springer CY - New York ER - TY - CHAP A1 - Doyon, Anke A1 - Schmiedchen, Bettina A1 - Bayazit, Aysun A1 - Canpolat, Nur A1 - Duzova, Ali A1 - Kracht, Daniela A1 - Litwin, Mieczyslaw A1 - Niemirska, Anna A1 - Sozeri, Betul A1 - Zeller, Rene A1 - Ranchin, Bruno A1 - Anarat, Ali A1 - Caliskan, Salim A1 - Mir, Sevgi A1 - Melk, Anette A1 - Wühl, Elke A1 - Schweigert, Florian J. A1 - Querfeld, Uwe A1 - Schäfer, Franz T1 - Distribuion and determinants of serum vitamin d concentrations in european children with chronic kidney disease T2 - Pediatric nephrology : journal of the International Pediatric Nephrology Association Y1 - 2012 SN - 0931-041X VL - 27 IS - 9 SP - 1627 EP - 1628 PB - Springer CY - New York ER - TY - GEN A1 - Hocher, Berthold A1 - Oberthür, Dominik A1 - Slowinski, Torsten A1 - Querfeld, Uwe A1 - Schaefer, Franz A1 - Doyon, Anke A1 - Tepel, Martin A1 - Roth, Heinz J. A1 - Grön, Hans J. A1 - Reichetzeder, Christoph A1 - Betzel, Christian A1 - Armbruster, Franz Paul T1 - Modeling of oxidized PTH (oxPTH) and non-oxidized PTH (n-oxPTH) receptor binding and relationship of oxidized to non-oxidized PTH in children with chronic renal failure, adult patients on hemodialysis and kidney transplant recipients N2 - Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH. We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 343 KW - n-oxPTH KW - chronic renal failure KW - kidney transplantation KW - hemodialysis KW - oxidation KW - PTH KW - chronic renal failure in children Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-399980 ER - TY - JOUR A1 - Hocher, Berthold A1 - Oberthür, Dominik A1 - Slowinski, Torsten A1 - Querfeld, Uwe A1 - Schäfer, Franz A1 - Doyon, Anke A1 - Tepel, Martin A1 - Roth, Heinz J. A1 - Grön, Hans J. A1 - Reichetzeder, Christoph A1 - Betzel, Christian A1 - Armbruster, Franz Paul T1 - Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH. We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. KW - n-oxPTH KW - Chronic Renal Failure KW - Kidney Transplantation KW - Hemodialysis KW - Oxidation KW - PTH KW - Chronic Renal Failure in Children Y1 - 2013 U6 - https://doi.org/10.1159/000350149 SN - 1420-4096 SN - 1423-0143 VL - 37 IS - 4-5 SP - 240 EP - 251 PB - Karger CY - Basel ER -