TY  - JOUR
A1  - Frey, Simone K.
A1  - Henze, Andrea
A1  - Nagl, Britta
A1  - Raila, Jens
A1  - Scholze, Alexandra
A1  - Tepel, Martin
A1  - Schweigert, Florian J.
A1  - Zidek, Walter
T1  - Effect of renal replacement therapy on retinol-binding protein 4 isoforms
N2  - 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.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00098981
U6  - https://doi.org/10.1016/j.cca.2008.11.008
SN  - 0009-8981
ER  - 
TY  - JOUR
A1  - Frey, Simone K.
A1  - Spranger, Joachim
A1  - Henze, Andrea
A1  - Pfeiffer, Andreas F. H.
A1  - Schweigert, Florian J.
A1  - Raila, Jens
T1  - Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus
N2  - Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00260495
U6  - https://doi.org/10.1016/j.metabol.2009.05.003
SN  - 0026-0495
ER  - 
TY  - THES
A1  - Henze, Andrea
T1  - Chronic kidney disease and type 2 diabetes mellitus as factors influencing retinol-binding protein 4
Y1  - 2009
CY  - Potsdam
ER  - 
TY  - JOUR
A1  - Bobbert, Thomas
A1  - Raila, Jens
A1  - Schwarz, Franziska
A1  - Mai, Knut
A1  - Henze, Andrea
A1  - Pfeiffer, Andreas F. H.
A1  - Schweigert, Florian J.
A1  - Spranger, Joachim
T1  - Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness
N2  - Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.
Y1  - 2010
UR  - http://www.sciencedirect.com/science/journal/00219150
U6  - https://doi.org/10.1016/j.atherosclerosis.2010.07.063
SN  - 0021-9150
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Frey, Simone K.
A1  - Raila, Jens
A1  - Scholze, Alexandra
A1  - Spranger, Joachim
A1  - Weickert, Martin O.
A1  - Tepel, Martin
A1  - Zidek, Walter
A1  - Schweigert, Florian J.
T1  - Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters
N2  - 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.
Y1  - 2010
UR  - http://www.sciencedirect.com/science/journal/0006291X
U6  - https://doi.org/10.1016/j.bbrc.2010.01.082
SN  - 0006-291X
ER  - 
TY  - JOUR
A1  - Thawnashom, Kittisak
A1  - Tungtrongchitr, Rungsunn
A1  - Chanchay, Siriporn
A1  - Tungtrongchitr, Anchalee
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Schweigert, Florian J.
T1  - Association between Retinol-Binding protein and renal function among Asian subjects with type 2 diabetes mellitus a cross-sectionaö study
JF  - The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED)
N2  - Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m(2) (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A - controls with an eGFR > 60 ml/min per 1.73 m(2), Group B - controls with an eGFR < 60 ml/min per 1.73 m(2), Group C- T2DM subjects with an eGFR>60 ml/min per 1.73 m(2), and Group D - T2DM subjects with an eGFR <60 ml/ mm per 1.73 m(2). In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m(2) than in subjects with an eGFR >60 ml/min per 1.73 m(2). However, the difference was only significant between the control groups (p <0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p<0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.
KW  - retinol-binding protein 4
KW  - renal function
KW  - type 2 diabetes mellitus
KW  - Asian subjects
Y1  - 2011
SN  - 0125-1562
VL  - 42
IS  - 4
SP  - 936
EP  - 945
PB  - SEAMEO
CY  - Bangkok
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Raila, Jens
A1  - Kempf, Caroline
A1  - Reinke, Petra
A1  - Sefrin, Anett
A1  - Querfeld, Uwe
A1  - Schweigert, Florian J.
T1  - Vitamin A metabolism is changed in donors after living-kidney transplantation an observational study
JF  - Lipids in health and disease
N2  - Background: The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
 Results: As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months.
 Conclusion: LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.
KW  - Donors
KW  - glomerular filtration rate
KW  - kidney transplantation
KW  - retinol
KW  - retinol-binding protein 4
KW  - transthyretin
Y1  - 2011
U6  - https://doi.org/10.1186/1476-511X-10-231
SN  - 1476-511X
VL  - 10
IS  - 23
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Krane, Vera
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Impact of vitamin A on clinical outcomes in haemodialysis patients
JF  - Nephrology, dialysis, transplantation
N2  - Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study.
 Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations.
 Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85).
 Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients.
KW  - haemodialysis
KW  - mortality
KW  - retinol
KW  - retinol-binding protein 4
KW  - sudden death
Y1  - 2011
U6  - https://doi.org/10.1093/ndt/gfr171
SN  - 0931-0509
VL  - 26
IS  - 12
SP  - 4054
EP  - U583
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Aumer, Franziska
A1  - Grabner, Arthur
A1  - Raila, Jens
A1  - Schweigert, Florian J.
T1  - Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling
JF  - The British journal of nutrition : an international journal devoted to the science of human and animal nutrition
N2  - Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.
KW  - Mass spectrometry
KW  - Post-translational modifications
KW  - Proteome
KW  - Species differences
Y1  - 2011
U6  - https://doi.org/10.1017/S0007114511000845
SN  - 0007-1145
VL  - 106
SP  - S170
EP  - S173
PB  - Cambridge Univ. Press
CY  - Cambridge
ER  - 
TY  - CHAP
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Blouin, Katja
A1  - Schneider, A.
A1  - Schmiedeke, D.
A1  - Krane, Vera
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients
T2  - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)
Y1  - 2012
SN  - 0250-6807
VL  - 60
IS  - 2
SP  - 137
EP  - 137
PB  - Karger
CY  - Basel
ER  -