Dagmar-Christiane Fischer

Semmelweis University, Budapeŝto, Budapest, Hungary

Are you Dagmar-Christiane Fischer?

Claim your profile

Publications (23)70.23 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Chronic inflammation may increase arterial stiffness. We tested whether arterial stiffness is increased children with asthma, a chronic disease characterized by fluctuating airway and systemic inflammation. Arterial stiffness, expressed as carotid-femoral pulse wave velocity (PWVcf), was measured in 37 mild-to-moderate asthmatic children: 11 girls, median (range) age 11.1 years (6-15). PWVcf in asthma was compared to PWVcf in 65 healthy controls matched for age, height, and gender previously studied in Germany and was correlated with airway inflammation and obstruction. PWVcf was higher in asthmatic children compared to controls: PWVcf median (interquartile range) was 4.7 m/s (4.5-4.9) vs. 4.3 m/s (4.1-4.7), p < 0.0001. In asthmatic children, PWVcf was inversely associated (r (2) = 0.20, p = 0.004) with forced expiratory volume in 1 s (FEV1). This association remained significant after adjusting for possible confounders including body mass index, blood pressure, steroid use, and FeNO. Conclusion: Arterial stiffness is increased in children with mild-to-moderate asthma. The association between impaired lung function and increased arterial stiffness suggests that severity of disease translates into detrimental effects on the cardiovascular system.
    European Journal of Pediatrics 09/2014; · 1.98 Impact Factor
  • Hagen Staude, Susann Jeske, Karin Schmitz, Gert Warncke, Dagmar-Christiane Fischer
    [Show abstract] [Hide abstract]
    ABSTRACT: The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i) biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification, and iii) an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.
    Kidney and Blood Pressure Research 03/2013; 37(1):68-83. · 1.60 Impact Factor
  • Journal of Hypertension 02/2013; 31(2):424-5. · 4.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P<0.0001); inflammation did not account for this difference. Multiple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the CT cohort, there was a positive association between the relative reduction of suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2 mutation had higher suPAR levels than those without a mutation. In conclusion, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. The associations between a change in circulating suPAR with different therapeutic regimens and with remission support the role of suPAR in the pathogenesis of FSGS.
    Journal of the American Society of Nephrology 11/2012; · 8.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Paediatric reference values for novel markers of phosphate homeostasis, bone formation and resorption and their putative relationship to growth are lacking. METHODS: A total of 424 healthy children, adolescents and young adults (221 males) aged 0.1-21 y, were enrolled in this cross-sectional study. Height, weight and height velocity were assessed. Plasma/serum samples for determination of C-terminal fragment of fibroblast growth factor-23 (cFGF-23), sclerostin, bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRAP5b) were available from 222, 264, 352 and 338 individuals, respectively. Calculation of cross-sectional centiles and z-scores was based on median (M), standard coefficient of variation (S) and the Box-Cox power (L) of transformation (LMS method) per age cohort. Correlations between variables as well as with growth were assessed. RESULTS: cFGF-23, BAP and TRAP5b were significantly correlated with age (each P < 0.01), with highest values during infancy and adolescence. Serum levels of BAP and TRAP5b were significantly higher in adolescent boys compared with girls (each P < 0.01). In contrast, sclerostin levels were independent of age and gender. BAP and TRAP5b were strongly correlated and both were significantly associated with cFGF-23 and sclerostin as well (each P < 0.01). cFGF-23 was positively correlated with serum phosphate and renal phosphate threshold concentration (each P < 0.01). Height, weight, body mass index and height velocity were weakly correlated with BAP and TRAP5b (each P < 0.05). CONCLUSIONS: This study provides age- and gender-related centile charts and z-scores for cFGF-23, BAP, TRAP5b and sclerostin and highlights the link between phosphate homeostasis and markers of bone metabolism during growth.
    Annals of Clinical Biochemistry 09/2012; · 1.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: : A semi-automated devise for oscillometric measurement (Vicorder) of carotid-femoral pulse wave velocity (cfPWV) has been considered to be especially suited for multicenter studies in children and adolescents. : Within a healthy pediatric population (156 boys/158 girls; mean age 10.8 years, range 5.0-19.6 years), the transit time of the pulse wave was measured oscillometrically (Vicorder) between a carotid and femoral cuff. For calculation of cfPWV, the traveled path length was set to 80% of the direct distance between both sites of measurement. Reference tables were generated using the maximum-likelihood curve-fitting technique and SD scores were calculated. Normalizing the same set of data with reference values specific for applanation tonometry yielded Zat values. Effects of sex, age, height, weight, BMI, blood pressure (BP), and heart rate on cfPWV as well as the correlation between sex-specific age-related and height-related Zosci and Zat were investigated. : Sex-specific reference values and curves for cfPWV as a function of age and height are presented. cfPWV correlated positively with age, height, weight, SBP, mean arterial BP, and sex (each P < 0.005). Multiple regression analysis identified age, sex, and mean arterial pressure as significant independent predictors of cfPWV explaining 42% of the overall variability. Strong linear relationships between Zosci and Zat were noted and per sex a set of age and height-related equation for conversion was derived: Zat,age = -0.22 + 0.68 × Zosci,age; r = 0.98 and Zat,height = -0.33 + 0.66 × Zosci,height; r = 0.99 in boys and Zat,age = -0.61 + 0.81 × Zosci,age; r = 0.98 and Zat,height = -0.73 + 0.72 × Zosci,height; r = 0.97 in girls (each P < 0.001). : A strong linear association between height-related oscillometric and tonometric Z-scores was observed. Age-related Z-scores are of limited value when comparing results across different populations and methods.
    Journal of Hypertension 08/2012; 30(11):2159-67. · 4.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vascular calcification, albeit heterogeneous in terms of biological and physicochemical properties, has been associated with ageing, lifestyle, diabetes, and chronic kidney disease (CKD). It is unknown whether or not moderately impaired renal function (CKD stages 2-4) affects the physiochemical composition and/or the formation of magnesium-containing tricalcium phosphate ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a high-resolution scanning X-ray diffraction analysis (European Synchrotron Radiation Facility, Grenoble, France) utilizing histological sections of paraffin-embedded arterial specimens derived from atherosclerotic patients with normal renal function (n = 15) and CKD (stages 2-4, n = 13) was performed. This approach allowed us to spatially assess the contribution of calcium phosphate (apatite) and whitlockite to arterial microcalcification. Per group, the number of samples (13 vs. 12) with sufficient signal intensity and total lengths of regions (201 vs. 232 μm) giving rise to diffractograms ("informative regions") were comparable. Summarizing all informative regions per group into one composite sample revealed calcium phosphate/apatite as the leading mineral phase in CKD patients, whereas in patients with normal renal function the relative contribution of whitlockite and calcium phosphate/apatite was on the same order of magnitude (CKD, calcium phosphate/apatite 157 μm, whitlockite 38.7 μm; non-CKD, calcium phosphate/apatite 79.0 μm, whitlockite 94.1 μm; each p < 0.05). Our results, although based on a limited number of samples, indicate that chronic impairment of renal function affects local magnesium homeostasis and thus contributes to the physicochemical composition of microcalcification in atherosclerotic patients.
    Calcified Tissue International 04/2012; 90(6):465-72. · 2.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, we identified a microduplication in chromosomal band 1q21.1 encompassing the CHD1L/ALC1 gene encoding a chromatin-remodelling enzyme in congenital anomalies of the kidneys and urinary tract (CAKUT) patient. To explore the role of CHD1L in CAKUT, we screened 85 CAKUT patients for mutations in the CHD1L gene and performed functional analyses of the three heterozygous missense variants detected. In addition, we quantitatively determined CHD1L expression in multiple human fetal and adult tissues and analysed expression of CHD1L protein in human embryonal, adult and hydronephrotic kidney sections. Two of three novel heterozygous missense variants identified in three patients were not found in >400 control chromosomes. All variants lead to amino acid substitutions in or near the CHD1L macro domain, a poly-ADP-ribose (PAR)-binding module interacting with PAR polymerase 1 (PARP1), and showed decreased interaction with PARP1 by pull-down assay of transfected cell lysates. Quantitative messenger RNA analysis demonstrated high CHD1L expression in human fetal kidneys, and levels were four times higher than in adult kidneys. In the human embryo at 7-11 weeks gestation, CHD1L immunolocalized in the early ureteric bud and the S- and comma-shaped bodies, critical stages of kidney development. In normal postnatal sections, CHD1L was expressed in the cytoplasm of tubular cells in all tubule segments. CHD1L expression appeared higher in the hydronephrotic kidney of one patient with a hypofunctional CHD1L variant than in normal kidneys, recapitulating high fetal levels. Our data suggest that CHD1L plays a role in kidney development and may be a new candidate gene for CAKUT.
    Nephrology Dialysis Transplantation 12/2011; 27(6):2355-64. · 3.37 Impact Factor
  • Dieter Haffner, Dagmar-Christiane Fischer
    [Show abstract] [Hide abstract]
    ABSTRACT: In patients with chronic kidney disease (CKD) renal osteodystrophy, in the form of either low- or high-turnover bone disease, is quite common. While renal transplantation is expected to reverse renal osteodystrophy, long-term treatment with glucocorticoids before and/or after transplantation may lead to osteoporosis instead. Osteoporosis is defined as a skeletal disease with low bone mineral density, microarchitectural deterioration, and concomitant fragility. In adults, bisphosphonates are widely used to treat osteoporosis and other diseases associated with excessive bone resorption. In pediatric CKD patients the efficacy and safety of these drugs have not yet been addressed adequately and thus no evidence-based recommendations regarding the optimal type of bisphosphonate, dosage, or duration of therapy are available. Furthermore, while in adults the determination of areal bone mineral density is sufficient to diagnose osteoporosis, this is not the case in children. Instead, in pediatric patients, careful morphological assessment of bone structure and formation is required. Indeed, data from studies with uremic rats indicated that bisphosphonates, via a deceleration of bone turnover, have the potential not only to aggravate pre-existing adynamic bone disease, but also to impair longitudinal growth. Thus, the widespread use of bisphosphonates in children with CKD should be discouraged until the risks and benefits have been carefully elucidated in clinical trials.
    Pediatric Nephrology 12/2011; 26(12):2111-9. · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The extracellular protein fetuin-A is a potent soluble inhibitor of calcification, and its deficiency has been associated with vascular calcification in dialysis patients. In proteinuric patients, significant urinary losses of fetuin-A may cause low serum fetuin-A levels. In a cross-sectional study, urinary/serum concentrations of fetuin-A were investigated in proteinuric children with glomerular diseases and preserved renal function (n = 58) in comparison to healthy controls (n = 246). Mean fetuin-A serum concentrations were clearly reduced in children with nephrotic syndrome (0.25 ± 0.14 g/l, p < 0.001), slightly reduced in children with large proteinuria (0.39 ± 0.15 g/l, p < 0.05), and comparable to controls in those with mild proteinuria (0.45 ± 0.14 vs. 0.46 ± 0.12 g/l). Fetuin-A was positively correlated with serum protein (r = 0.58), albumin (r = 0.57), and calcium (r = 0.64), but negatively correlated with proteinuria (r = -0.41), albuminuria (r = -0.46), and urinary fetuin-A excretion (r = -0.48; each p < 0.001). The fractional excretion of fetuin-A was significantly associated with the degree of proteinuria and serum fetuin-A levels. However, the urinary loss of fetuin-A and albumin in nephrotic children differed by three orders of magnitude and the mean fractional excretion of fetuin-A was only 1/10 of that of albumin (0.016 ± 0.029 vs. 0.162 ± 0.403%; p < 0.001). Fetuin-A is clearly reduced in children with nephrotic syndrome and associated with the degree of hypoalbuminemia. This is due to urinary fetuin-A loss and/or reduced hepatic synthesis. Persistent fetuin-A deficiency may have an impact on cardiovascular morbidity in nephrotic children.
    American Journal of Nephrology 09/2011; 34(4):373-80. · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fetuin-A and vitamin D are significant correlates of cardiovascular morbidity in paediatric chronic kidney disease (CKD) patients. It is thus far unknown, whether or not serum fetuin-A is affected by the vitamin D status or treatment with vitamin D preparations in these patients. In a cross-sectional study, serum concentrations of fetuin-A, 25-hydroxyvitamin D(3) (25OHD) and 1,25-dihydroxyvitamin D(3) (calcitriol) levels were determined in 112 paediatric patients with mild-to-severe CKD (Stages 1-5) and after renal transplantation. A25OHD supplementation and/or calcitriol treatment were given in 64% of the patients. Fetuin-A levels were clearly reduced in dialysis patients but were comparable to healthy controls in those with moderate CKD and after transplantation. Although 64 and 46% of all patients received 25OHD and/or calcitriol treatment, 48 and 20% of patients were 25OHD and/or calcitriol deficient, respectively. Within the whole patient cohort, fetuin-A correlated with serum calcium and yearly weight-related 25OHD dosage (each P < 0.01) but not with the vitamin D status per se. Multiple regression analysis revealed the need for dialysis treatment and cumulative 25OHD dosage as independent predictors of fetuin-A concentrations (model r(2) = 0.17). In dialysis patients, fetuin-A was inversely correlated with serum C-reactive protein but positively correlated with cumulative calcitriol dosage and serum parathormone (each P < 0.01). Fetuin-A levels are clearly reduced in children on dialysis but not in those with moderate CKD and after transplantation. Besides the degree of microinflammation, the cumulative intake of 25OHD and calcitriol are significantly correlated to fetuin-A in these patients. The impact of vitamin D treatment appears to be at least partly mediated by serum calcium.
    Nephrology Dialysis Transplantation 07/2011; 27(3):1107-13. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal osteodystrophy and eventually osteoporosis are serious long-term complications in children with end-stage renal disease before and after renal transplantation. Strontium (Sr) salts are used for treatment of osteoporosis in adults. To evaluate the time-dependent effects of Sr on growth plate morphology and their reversibility, chronic renal failure (CRF) rats received either normal or Sr-loaded drinking water (2 g/l; ±200 mg/kg/day) for periods of 2, 6 and 12 weeks with or without subsequent washout periods of 0, 2, 4 or 8 weeks. While weight gain was not affected by Sr loading, a significant enlargement of the entire growth plate, mainly due to expansion of the hypertrophic zone, was already present after 2 weeks. Sr-loaded animals showed increased osteoid areas and reduced bone formation rates at 2, 6 and 12 weeks compared to controls. This was accompanied by reduced PTH levels and increased serum bone alkaline phosphatase activity. After the washout periods these effects were reversed. In general, the height of the hypertrophic zone was positively correlated with osteoid area and negatively correlated with bone formation rate. Moderate Sr loading in CRF rats results in rapid development of rickets, which is reversible after washout.
    Kidney and Blood Pressure Research 06/2011; 34(6):375-81. · 1.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activation of the mTOR pathway has been implicated in the mediation of the progression of polycystic kidney disease (PKD). Whereas targeted inhibition of mTOR has been proven to be effective in various animal models of autosomal dominant PKD, its efficacy in autosomal recessive PKD (ARPKD) remains to be elucidated. We examined the effects of sirolimus in PCK rats, an orthologous animal model of human ARPKD. Weaned PCK rats (n = 85) and SD-control rats (n = 72) received drinking water without and with sirolimus (corresponding to a daily intake of 2 mg/kg body weight) for 4, 8 and 12 weeks, respectively. The renal and hepatic functions were monitored throughout the treatment periods. Kidneys and livers were harvested and investigated with respect to progression of fibrosis, and number and size of cysts using the QWin image analysis programme. Expression of Akt, mTOR and its downstream target pS6K were assessed by immunohistochemistry. Five out of 43 sirolimus-treated PCK rats, but none of the controls, died during the study. Sirolimus treatment resulted in slightly reduced weight gain. In PCK rats, grossly enlarged kidney and livers as well as hepatic fibrosis together with enlarged bile ducts were readily detectable. Whereas activation of Akt/mTOR signalling was hardly detectable in the kidneys of SD rats, strong signals were seen in the kidneys of PCK rats. Despite a significantly reduced relative kidney weight after 12 weeks of treatment (P < 0.05), neither fibrosis and cyst area nor renal function improved during treatment. Sirolimus-treated PCK rats showed only a minor inhibition of renal mTOR-specific phosphorylation of S6K. Male PCK rats on sirolimus presented with increased concentrations of bile acids and bilirubin compared with controls (each P < 0.05 at 12 weeks). Similar, albeit non-significant, effects were noted in female PCK rats. Sirolimus failed to attenuate progression of kidney and liver disease in PCK rats. The lack of a protective effect might be due to intrinsic or acquired rapamycin resistance in this animal model of ARPKD.
    Nephrology Dialysis Transplantation 01/2011; 26(1):92-100. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bisphosphonates have been shown to attenuate ectopic calcification in experimental uremia. While they are known to reduce bone turnover, the effects on endochondral bone formation have not yet been addressed. To address this issue, we administered male Sprague-Dawley rats weekly subcutaneous injections of either vehicle or ibandronate (1.25 μg/kg body weight) for a total of 10 weeks. The rats were randomly allocated into one of four groups: (1) vehicle-treated, sham-operated rats; (2) ibandronate-treated, sham-operated rats; (3) vehicle-treated, 5/6 nephrectomized rats; (4) ibandronate-treated, 5/6 nephrectomized rats. Bones were double labeled with tetracycline and demeclocycline in vivo, and tibiae were removed for analysis. Weight gain was similar in all groups. Ibandronate reduced body length gain and tibial growth rate in the sham-operated animals but not in the rats showing chronic renal failure (CRF). The height of the proliferative zone of the epiphyseal growth plate was reduced in the ibandronate-treated controls and tended to be reduced in CRF rats. A significant correlation between tibial growth rate and height of the proliferative zone was observed. Mineral apposition rates were significantly reduced in ibandronate-treated, sham-operated rats and tended to be reduced in CRF rats. In conclusion, ibandronate interferes with tibial growth and bone mineralization in young rats with normal and reduced renal function.
    Pediatric Nephrology 10/2010; 26(1):111-7. · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human atheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral-loaded fetuin-A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)-23 to ectopic mineralization. Serial sections of formalin-fixed paraffin-embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin-A and FGF-23. All specimens were calcified and SOX-9, collagen type II, cathepsin-K, fetuin-A and FGF-23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF-23 (45/48) indicates local synthesis. Whereas fetuin-A expression was seen also within areas of vascular smooth muscle actin-positive cells adjacent to calcific deposits, FGF-23 expression was apparently restricted to the mineralization-prone areas. Both local expression and FGF-23 serum concentrations were significantly associated with the degree of atheroma calcification. Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin-A-attracting microenvironment. FGF-23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.
    Histopathology 05/2010; 56(6):775-88. · 2.86 Impact Factor
  • Source
    Dieter Haffner, Dagmar-Christiane Fischer
    [Show abstract] [Hide abstract]
    ABSTRACT: Idiopathic nephrotic syndrome is the most frequent glomerular disease that presents during childhood and is mainly due to minimal change nephropathy (MCNS) and focal-segmental glomerulosclerosis (FSGS). Its treatment is still challenging, with up to 50% of the patients who are initially steroid sensitive (usually MCNS) being frequent relapsers and requiring additional long-term immunosuppression. However, current immunosuppressive regimens are associated with severe toxicity. Only half of the steroid-resistant patients (usually FSGS) achieve long-term remission even with intensive immunosuppression and plasma exchange. Rituximab (RTX), a chimeric monoclonal antibody inhibiting CD20-mediated B-cell proliferation and differentiation, has recently gained attention as a potentially successful therapy for complicated idiopathic nephrotic syndrome in children. A number of case reports and one prospective non-controlled multicenter trial point to the beneficial effects of RTX as a rescue therapy in children with steroid/cyclosporine-dependent or -resistant nephrotic syndrome. However, publication bias often results in positive outcomes being more likely to be reported than negative ones and, in particular, the safety profile of this drug in this group of patients remains unclear. Therefore, controlled randomized studies are required to assess this issue, to develop treatment guidelines, to evaluate the therapeutic and economical efficacy, and to define criteria for the selection of patients.
    Pediatric Nephrology 09/2009; 24(8):1433-8. · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Serum fetuin-A has been shown to be a strong risk marker for myocardial infarction/stroke in the general population, and has been associated with vascular calcifications in patients with chronic kidney disease. Although these issues are worthy of being addressed in children and adolescents as well, adequate age- and gender-related reference values are missing. Within a healthy paediatric population (n = 246), fetuin-A serum concentrations were determined (ELISA kit; Epitope Diagnostics, San Diego, CA, USA) essentially as described by the manufacturer. At the same time, serum protein and serum albumin were measured with established procedures (Beckman Coulter Inc., Krefeld, Germany). Subjects were stratified according to age (<1 yr [n = 25], > or =1 and <6 yr [n = 65], > or =6 and <12 yr [n = 66], > or =12 yr and <16 [n = 45] and > or =16 yr [n = 45]), and both genders were equally distributed within each age cohort. Within each age cohort, fetuin-A serum concentrations were normally distributed, independent of age and gender and the respective reference range (mean +/- 1.96 SD) is 0.22-0.70 g/L (0.46 +/- 0.24 g/L). Fetuin-A serum concentrations are independent of age and gender in a healthy paediatric population and are well comparable with those determined in adults with the same assay.
    Annals of Clinical Biochemistry 09/2009; 46(Pt 6):511-3. · 1.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and contributes significantly to the high long-term cardiovascular morbidity and mortality. The short-term cardiovascular effects of recombinant human growth hormone (rhGH) in CKD patients (stages III-V) and healthy controls (n=15 each) were explored in a single-center, non-randomized pilot study. Subjects were investigated before, after a 7 day treatment with rhGH, and after a 7 day wash-out period. Microcirculation was assessed by nailfold capillaroscopy and leg strain gauge plethysmography. Echocardiography was performed and serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) were determined. Before the start of rhGH therapy, mean post-ischemic maximum flow velocity of erythrocytes (V(RBC)) and leg blood flow (LBF) in CKD patients were significantly reduced to 68% and 75% of that seen in controls, whereas V(RBC) and LBF under resting conditions were comparable. Treatment with rhGH significantly increased V(RBC) and LBF under resting conditions. Whereas maximum post-ischemic V(RBC) was improved by rhGH in patients and controls, maximum post-ischemic LBF increased in controls only. This was paralleled by a non-significant reduction of total vascular resistance, and increased heart rate and cardiac index. In conclusion, CKD patients respond to short-term rhGH treatment with significantly improved capillary blood flow, whereas only minor effects on total peripheral resistance and cardiac output were noted.
    Microvascular Research 07/2009; 78(2):246-52. · 2.93 Impact Factor
  • Source
    Dieter Haffner, Dagmar-Christiane Fischer
    [Show abstract] [Hide abstract]
    ABSTRACT: Growth failure is still a challenge in infants suffering from chronic kidney disease (CKD). Persistent growth failure is associated with the excessive mortality rate seen in these patients and markedly hampers later psychosocial integration. Infancy is an extremely sensitive period of growth, since physiological growth rates are several times higher than in later life. Growth failure in infants with CKD has multiple reasons, originating preferentially from malnutrition and, to a lesser extent, from water and electrolyte losses, metabolic acidosis, anemia, and renal osteodystrophy. Although, recombinant human growth hormone (rhGH) has been proven to be safe and effective for treatment of uremic growth failure in later childhood, its usage has not been adequately investigated in infants. Mencarelli et al. (Pediatric Nephrology 24:1039-1046, 2009) reported on their retrospective analysis of the longitudinal growth of 27 infants with early onset CKD that were receiving either standard therapy or additional rhGH treatment. Although their results were encouraging with respect to a sustained catch-up growth in rhGH-treated children, this issue has to be further addressed in prospective randomized controlled trials. In these trials special emphasis has to be given to the safety of this treatment modality, since rhGH might induce insulin resistance and glucose intolerance, especially in infants on high caloric intake and peritoneal dialysis.
    Pediatric Nephrology 05/2009; 24(6):1097-100. · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autosomal recessive polycystic kidney disease (ARPKD) [MIM 263200] belongs to a group of congenital hepatorenal fibrocystic syndromes and is caused by mutations in the PKHD1 gene encoding the multidomain protein fibrocystin/polyductin (FPC). The serine-threonine kinase mammalian target of rapamycin (mTOR) is one of the most important gate-keepers integrating numerous signals related to cell proliferation and growth. Whereas the direct activation of mTOR has been shown recently in autosomal-dominant PKD, no data are available on the role of mTOR signalling in proliferation and progression of ARPKD. Formalin-fixed and paraffin-embedded kidney specimens obtained during nephrectomy from children with ARPKD (n = 12) were used for immunohistochemical investigation of FPC expression (monoclonal antibody (mAb) 18, mAb 5a), proliferative activity (Ki-67) and activation of the mTOR pathway. Kidney specimens from children (n = 4) who died from causes not associated with kidney disease served as controls. For the detection of AKT, mTOR and S6K antibodies specifically recognizing the activated (phosphorylated) isoforms of these proteins were used. In all patients mutation analysis of the PKHD1 gene was performed. In 10 out of 12 patients, we could confirm the diagnosis by the identification of PKHD1 mutations. The tubular cyst epithelium of all kidney specimens stained strongly positive with the FPC-specific monoclonal antibody (mAb) 18 but only very faint signals were obtained with mAb 5a. In contrast, healthy kidneys showed rather weak signals with both FPC-specific mAbs, indicating dysregulated expression of FPC in our patients. Phosphorylated AKT as well as activated mTOR and its down-stream effector S6K were strongly expressed in cystic epithelia of all kidney specimens but not in control tissues. No association between the activation of this pathway and the proliferative activity (Ki-67 expression) was observed. Our results point to a central role of AKT/mTOR signalling in ARPKD and justify further investigations to evaluate the therapeutic potential of mTOR inhibitors in ARPKD patients.
    Nephrology Dialysis Transplantation 02/2009; 24(6):1819-27. · 3.37 Impact Factor

Publication Stats

184 Citations
70.23 Total Impact Points

Institutions

  • 2013
    • Semmelweis University
      • First Department of Paediatrics
      Budapeŝto, Budapest, Hungary
  • 2008–2013
    • University of Rostock
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2011
    • Hannover Medical School
      Hanover, Lower Saxony, Germany