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  - Kumar, Reddi K.
A1  - Heuchel, Matthias
A1  - Kratz, Karl
A1  - Lendlein, Andreas
A1  - Jankowski, Joachim
A1  - Tetali, Sarada D.
T1  - Effects of extracts prepared from modified porous poly(ether imide) microparticulate absorbers on cytotoxicity, macrophage differentiation and proinflammatory behavior of human monocytic (THP-1) cells
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment.
KW  - Chronic kidney disease
KW  - hemodialysis
KW  - Inflammation
KW  - Porous poly(ether imide) microparticulate absorbers
KW  - THP-1 cells
KW  - Uremic toxins
Y1  - 2018
U6  - https://doi.org/10.3233/CH-189112
SN  - 1386-0291
SN  - 1875-8622
VL  - 69
IS  - 1-2
SP  - 175
EP  - 185
PB  - IOS Press
CY  - Amsterdam
ER  -