This page has only limited features, please log in for full access.

Dr. Maren Leifheit-Nestler
Hannover Medical School, Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover, Germany

Basic Info


Research Keywords & Expertise

0 Animal Models
0 Chronic Kidney Disease
0 cardiorenal syndrome
0 Cardiac remodeling
0 Fibroblast Growth Factor 23

Fingerprints

Fibroblast Growth Factor 23
Chronic Kidney Disease
Mineral and bone disorder
Cardiac remodeling

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Review article
Published: 04 August 2021 in Frontiers in Pediatrics
Reads 0
Downloads 0

Cardiovascular diseases (CVD) are a hallmark in pediatric patients with chronic kidney disease (CKD) contributing to an enhanced risk of all-cause and CV morbidity and mortality in these patients. The bone-derived phosphaturic hormone fibroblast growth factor (FGF) 23 progressively rises with declining kidney function to maintain phosphate homeostasis, with up to 1,000-fold increase in patients with kidney failure requiring dialysis. FGF23 is associated with the development of left ventricular hypertrophy (LVH) and thereby accounts to be a CVD risk factor in CKD. Experimentally, FGF23 directly induces hypertrophic growth of cardiac myocytes in vitro and LVH in vivo. Further, clinical studies in adult CKD have observed cardiotoxicity associated with FGF23. Data regarding prevalence and determinants of FGF23 excess in children with CKD are limited. This review summarizes current data and discusses whether FGF23 may be a key driver of LVH in pediatric CKD.

ACS Style

Andrea Grund; Manish D. Sinha; Dieter Haffner; Maren Leifheit-Nestler. Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective. Frontiers in Pediatrics 2021, 9, 1 .

AMA Style

Andrea Grund, Manish D. Sinha, Dieter Haffner, Maren Leifheit-Nestler. Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective. Frontiers in Pediatrics. 2021; 9 ():1.

Chicago/Turabian Style

Andrea Grund; Manish D. Sinha; Dieter Haffner; Maren Leifheit-Nestler. 2021. "Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective." Frontiers in Pediatrics 9, no. : 1.

Journal article
Published: 30 November 2020 in Nephrology Dialysis Transplantation
Reads 0
Downloads 0

Background Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin–angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. Methods In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case–control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3–5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. Results In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. Conclusions Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3–5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.

ACS Style

Anne Schön; Maren Leifheit-Nestler; Jennifer Deppe; Dagmar-Christiane Fischer; Aysun K Bayazit; Lukasz Obrycki; Nur Canpolat; Ipek Kaplan Bulut; Karolis Azukaitis; Alev Yilmaz; Sevgi Mir; Fatos Yalcinkaya; Oguz Soylemezoglu; Anette Melk; Gabriele I Stangl; Rouven Behnisch; Rukshana Shroff; Justine Bacchetta; Uwe Querfeld; Franz Schaefer; Dieter Haffner; for the 4C and Study Consortium and the ESPN CKD-MBD Working Group. Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3–5. Nephrology Dialysis Transplantation 2020, 36, 442 -451.

AMA Style

Anne Schön, Maren Leifheit-Nestler, Jennifer Deppe, Dagmar-Christiane Fischer, Aysun K Bayazit, Lukasz Obrycki, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Alev Yilmaz, Sevgi Mir, Fatos Yalcinkaya, Oguz Soylemezoglu, Anette Melk, Gabriele I Stangl, Rouven Behnisch, Rukshana Shroff, Justine Bacchetta, Uwe Querfeld, Franz Schaefer, Dieter Haffner, for the 4C and Study Consortium and the ESPN CKD-MBD Working Group. Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3–5. Nephrology Dialysis Transplantation. 2020; 36 (3):442-451.

Chicago/Turabian Style

Anne Schön; Maren Leifheit-Nestler; Jennifer Deppe; Dagmar-Christiane Fischer; Aysun K Bayazit; Lukasz Obrycki; Nur Canpolat; Ipek Kaplan Bulut; Karolis Azukaitis; Alev Yilmaz; Sevgi Mir; Fatos Yalcinkaya; Oguz Soylemezoglu; Anette Melk; Gabriele I Stangl; Rouven Behnisch; Rukshana Shroff; Justine Bacchetta; Uwe Querfeld; Franz Schaefer; Dieter Haffner; for the 4C and Study Consortium and the ESPN CKD-MBD Working Group. 2020. "Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3–5." Nephrology Dialysis Transplantation 36, no. 3: 442-451.

Journal article
Published: 02 November 2020 in Nephrology Dialysis Transplantation
Reads 0
Downloads 0

Mineral and bone disorder (MBD) is widely prevalent in children with chronic kidney disease (CKD) and is associated with significant morbidity. CKD may cause disturbances in bone remodelling/modelling, which are more pronounced in the growing skeleton, manifesting as short stature, bone pain and deformities, fractures, slipped epiphyses and ectopic calcifications. Although assessment of bone health is a key element in the clinical care of children with CKD, it remains a major challenge for physicians. On the one hand, bone biopsy with histomorphometry is the gold standard for assessing bone health, but it is expensive, invasive and requires expertise in the interpretation of bone histology. On the other hand, currently available non-invasive measures, including dual-energy X-ray absorptiometry and biomarkers of bone formation/resorption, are affected by growth and pubertal status and have limited sensitivity and specificity in predicting changes in bone turnover and mineralization. In the absence of high-quality evidence, there are wide variations in clinical practice in the diagnosis and management of CKD-MBD in childhood. We present clinical practice points (CPPs) on the assessment of bone disease in children with CKD Stages 2–5 and on dialysis based on the best available evidence and consensus of experts from the CKD-MBD and Dialysis working groups of the European Society for Paediatric Nephrology and the CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association. These CPPs should be carefully considered by treating physicians and adapted to individual patients’ needs as appropriate. Further areas for research are suggested.

ACS Style

Sevcan A Bakkaloglu; Justine Bacchetta; Alexander D Lalayiannis; Maren Leifheit-Nestler; Stella Stabouli; Mathias Haarhaus; George Reusz; Jaap Groothoff; Claus Peter Schmitt; Pieter Evenepoel; Rukshana Shroff; Dieter Haffner; the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA. Nephrology Dialysis Transplantation 2020, 36, 413 -425.

AMA Style

Sevcan A Bakkaloglu, Justine Bacchetta, Alexander D Lalayiannis, Maren Leifheit-Nestler, Stella Stabouli, Mathias Haarhaus, George Reusz, Jaap Groothoff, Claus Peter Schmitt, Pieter Evenepoel, Rukshana Shroff, Dieter Haffner, the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA. Nephrology Dialysis Transplantation. 2020; 36 (3):413-425.

Chicago/Turabian Style

Sevcan A Bakkaloglu; Justine Bacchetta; Alexander D Lalayiannis; Maren Leifheit-Nestler; Stella Stabouli; Mathias Haarhaus; George Reusz; Jaap Groothoff; Claus Peter Schmitt; Pieter Evenepoel; Rukshana Shroff; Dieter Haffner; the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. 2020. "Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA." Nephrology Dialysis Transplantation 36, no. 3: 413-425.

Scholarlyarticle
Published: 15 May 2020 in The Journal of Clinical Endocrinology & Metabolism
Reads 0
Downloads 0

Context Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking. Objective To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD. Design Cross-sectional multicenter study. Setting Hospital clinics. Patients Forty-nine children with NC, 80 CKD controls of the same age and CKD stage. Main outcome measures Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity. Results Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate. Conclusions Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.

ACS Style

Annika Ewert; Maren Leifheit-Nestler; Katharina Hohenfellner; Anja Büscher; Markus J Kemper; Jun Oh; Heiko Billing; Julia Thumfart; Gabriele Stangl; Anja C Baur; Michael Föller; Martina Feger; Lutz T Weber; Birgit Acham-Roschitz; Klaus Arbeiter; Burkhard Tönshoff; Miroslav Zivicnjak; Dieter Haffner. Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities. The Journal of Clinical Endocrinology & Metabolism 2020, 105, 1 .

AMA Style

Annika Ewert, Maren Leifheit-Nestler, Katharina Hohenfellner, Anja Büscher, Markus J Kemper, Jun Oh, Heiko Billing, Julia Thumfart, Gabriele Stangl, Anja C Baur, Michael Föller, Martina Feger, Lutz T Weber, Birgit Acham-Roschitz, Klaus Arbeiter, Burkhard Tönshoff, Miroslav Zivicnjak, Dieter Haffner. Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities. The Journal of Clinical Endocrinology & Metabolism. 2020; 105 (8):1.

Chicago/Turabian Style

Annika Ewert; Maren Leifheit-Nestler; Katharina Hohenfellner; Anja Büscher; Markus J Kemper; Jun Oh; Heiko Billing; Julia Thumfart; Gabriele Stangl; Anja C Baur; Michael Föller; Martina Feger; Lutz T Weber; Birgit Acham-Roschitz; Klaus Arbeiter; Burkhard Tönshoff; Miroslav Zivicnjak; Dieter Haffner. 2020. "Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities." The Journal of Clinical Endocrinology & Metabolism 105, no. 8: 1.

Educational review
Published: 19 December 2019 in Pediatric Nephrology
Reads 0
Downloads 0

Complications of chronic kidney disease-associated mineral and bone disorders (CKD-MBD) are frequently observed in pediatric kidney transplant recipients and are associated with high morbidity, including growth failure, leg deformities, bone pain, fractures, osteonecrosis, and vascular calcification. Post-transplant CKD-MBD is mainly due to preexisting renal osteodystrophy and cardiovascular changes at the time of transplantation, glucocorticoid treatment, and reduced graft function. In addition, persistent elevated levels of parathyroid hormone (PTH) and fibroblast growth factor 23 may cause hypophosphatemia, resulting in impaired bone mineralization. Patient monitoring should include assessment of growth, leg deformities, and serum levels of calcium, phosphate, magnesium, alkaline phosphatase, 25-hydroxyvitamin D, and PTH. Therapy should primarily focus on regular physical activity, preservation of transplant function, and steroid-sparing immunosuppressive protocols. In addition, adequate monitoring and treatment of vitamin D and mineral metabolism including vitamin D supplementation, oral phosphate, and/or magnesium supplementation, in case of persistent hypophosphatemia/hypomagnesemia, and treatment with active vitamin D in cases of persistent secondary hyperparathyroidism. The latter should be done using the minimum PTH-suppressive dosages aiming at the recommended CKD stage-dependent PTH target range. Finally, treatment with recombinant human growth hormone should be considered in patients lacking catch-up growth within the first year after transplantation.

ACS Style

Dieter Haffner; Maren Leifheit-Nestler. CKD-MBD post kidney transplantation. Pediatric Nephrology 2019, 36, 41 -50.

AMA Style

Dieter Haffner, Maren Leifheit-Nestler. CKD-MBD post kidney transplantation. Pediatric Nephrology. 2019; 36 (1):41-50.

Chicago/Turabian Style

Dieter Haffner; Maren Leifheit-Nestler. 2019. "CKD-MBD post kidney transplantation." Pediatric Nephrology 36, no. 1: 41-50.

Review
Published: 10 December 2019 in Pediatric Nephrology
Reads 0
Downloads 0

Secondary hyperparathyroidism is part of the complex of chronic kidney disease-associated mineral and bone disorders (CKD-MBD) and is linked with high bone turnover, ectopic calcification, and increased cardiovascular mortality. Therefore, measures for CKD-MBD aim at lowering PTH levels, but there is no general consensus on optimal PTH target values. This manuscript is part of a pros and cons debate for keeping PTH levels within the normal range in children with CKD, focusing on the cons. We conclude that a modest increase in PTH most likely represents an appropriate adaptive response to declining kidney function in patients with CKD stages 2–5D, due to phosphaturic effects and increasing bone resistance. There is no evidence for strictly keeping PTH levels within the normal range in CKD patients with respect to bone health and cardiovascular outcome. In addition, the potentially adverse effects of PTH-lowering measures, such as active vitamin D and calcimimetics, must be taken into account. We suggest that PTH values of 1–2 times the upper normal limit (ULN) may be acceptable in children with CKD stage 2–3, and that PTH levels of 1.7–5 times UNL may be optimal in patients with CKD stage 4–5D. However, standard care of CKD-MBD in children relies on a combination of different measures in which the observation of PTH levels is only a small part of, and trends in PTH levels rather than absolute target values should determine treatment decisions in patients with CKD as recommended by the 2017 KDIGO guidelines.

ACS Style

Dieter Haffner; Maren Leifheit-Nestler. Treatment of hyperphosphatemia: the dangers of aiming for normal PTH levels. Pediatric Nephrology 2019, 35, 485 -491.

AMA Style

Dieter Haffner, Maren Leifheit-Nestler. Treatment of hyperphosphatemia: the dangers of aiming for normal PTH levels. Pediatric Nephrology. 2019; 35 (3):485-491.

Chicago/Turabian Style

Dieter Haffner; Maren Leifheit-Nestler. 2019. "Treatment of hyperphosphatemia: the dangers of aiming for normal PTH levels." Pediatric Nephrology 35, no. 3: 485-491.

Original paper
Published: 23 November 2019 in European Archives of Psychiatry and Clinical Neuroscience
Reads 0
Downloads 0

For patients with depression treated with electroconvulsive therapy (ECT), the novel seizure quality index (SQI) can predict the risk of non-response (and non-remission)—as early as after the second ECT session—based the extent of several ictal parameters of the seizure. We aim to test several CSF markers on their ability to predict the degree of seizure quality, measured by the SQI to identify possible factors, that could explain some variability of the seizure quality. Baseline CSF levels of metabolites from the kynurenine pathway, markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system, endocannabinoids, sphingolipids, neurotrophic factors (VEGF) and Klotho were measured before ECT in patients with depression (n = 12) to identify possible correlations with the SQI by Pearson's partial correlation. Negative, linear relationships with the SQI for response were observed for CSF levels of T-tau (rpartial = − 0.69, p = 0.019), phosphatidylcholines (rpartial = − 0.52, p = 0.038) and IL-8 (rpartial = − 0.67, p = 0.047). Regarding the SQI for remission, a negative, linear relationship was noted with CSF levels of the endocannabinoid AEA (rpartial = − 0.70, p = 0.024) and CD163 (rpartial = − 0.68, p = 0.029). In sum, CSF Markers for the innate immune system, for neurodegeneration and from lipids were found to be associated with the SQI for response and remission after adjusting for age. Consistently, higher CSF levels of the markers were always associated with lower seizure quality. Based on these results, further research regarding the mechanism of seizure quality in ECT is suggested.

ACS Style

Laura Kranaster; Carolin Hoyer; Sonani Mindt; Michael Neumaier; Norbert Müller; Peter Zill; Markus J. Schwarz; Natalie Moll; Beat Lutz; Laura Bindila; Inga Zerr; Matthias Schmitz; Kaj Blennow; Henrik Zetterberg; Dieter Haffner; Maren Leifheit-Nestler; Cagakan Ozbalci; Alexander Sartorius. The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid. European Archives of Psychiatry and Clinical Neuroscience 2019, 270, 1 -9.

AMA Style

Laura Kranaster, Carolin Hoyer, Sonani Mindt, Michael Neumaier, Norbert Müller, Peter Zill, Markus J. Schwarz, Natalie Moll, Beat Lutz, Laura Bindila, Inga Zerr, Matthias Schmitz, Kaj Blennow, Henrik Zetterberg, Dieter Haffner, Maren Leifheit-Nestler, Cagakan Ozbalci, Alexander Sartorius. The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid. European Archives of Psychiatry and Clinical Neuroscience. 2019; 270 (7):1-9.

Chicago/Turabian Style

Laura Kranaster; Carolin Hoyer; Sonani Mindt; Michael Neumaier; Norbert Müller; Peter Zill; Markus J. Schwarz; Natalie Moll; Beat Lutz; Laura Bindila; Inga Zerr; Matthias Schmitz; Kaj Blennow; Henrik Zetterberg; Dieter Haffner; Maren Leifheit-Nestler; Cagakan Ozbalci; Alexander Sartorius. 2019. "The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid." European Archives of Psychiatry and Clinical Neuroscience 270, no. 7: 1-9.

Review
Published: 06 November 2019 in Toxins
Reads 0
Downloads 0

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.

ACS Style

Isabel Vogt; Dieter Haffner; Maren Leifheit-Nestler; Vogt; Leifheit- Nestler. FGF23 and Phosphate–Cardiovascular Toxins in CKD. Toxins 2019, 11, 647 .

AMA Style

Isabel Vogt, Dieter Haffner, Maren Leifheit-Nestler, Vogt, Leifheit- Nestler. FGF23 and Phosphate–Cardiovascular Toxins in CKD. Toxins. 2019; 11 (11):647.

Chicago/Turabian Style

Isabel Vogt; Dieter Haffner; Maren Leifheit-Nestler; Vogt; Leifheit- Nestler. 2019. "FGF23 and Phosphate–Cardiovascular Toxins in CKD." Toxins 11, no. 11: 647.

Journal article
Published: 18 September 2019 in International Journal of Molecular Sciences
Reads 0
Downloads 0

Patients with chronic kidney disease (CKD) are prone to developing cardiac hypertrophy and fibrosis, which is associated with increased fibroblast growth factor 23 (FGF23) serum levels. Elevated circulating FGF23 was shown to induce left ventricular hypertrophy (LVH) via the calcineurin/NFAT pathway and contributed to cardiac fibrosis by stimulation of profibrotic factors. We hypothesized that FGF23 may also stimulate the local renin–angiotensin–aldosterone system (RAAS) in the heart, thereby further promoting the progression of FGF23-mediated cardiac pathologies. We evaluated LVH and fibrosis in association with cardiac FGF23 and activation of RAAS in heart tissue of 5/6 nephrectomized (5/6Nx) rats compared to sham-operated animals followed by in vitro studies with isolated neonatal rat ventricular myocytes and fibroblast (NRVM, NRCF), respectively. Uremic rats showed enhanced cardiomyocyte size and cardiac fibrosis compared with sham. The cardiac expression of Fgf23 and RAAS genes were increased in 5/6Nx rats and correlated with the degree of cardiac fibrosis. In NRVM and NRCF, FGF23 stimulated the expression of RAAS genes and induced Ngal indicating mineralocorticoid receptor activation. The FGF23-mediated hypertrophic growth of NRVM and induction of NFAT target genes were attenuated by cyclosporine A, losartan and spironolactone. In NRCF, FGF23 induced Tgfb and Ctgf, which were suppressed by losartan and spironolactone, only. Our data suggest that FGF23-mediated activation of local RAAS in the heart promotes cardiac hypertrophy and fibrosis.

ACS Style

Ineke Böckmann; Jonas Lischka; Beatrice Richter; Jennifer Deppe; Anja Rahn; Dagmar-Christiane Fischer; Jörg Heineke; Dieter Haffner; Maren Leifheit-Nestler. FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis. International Journal of Molecular Sciences 2019, 20, 4634 .

AMA Style

Ineke Böckmann, Jonas Lischka, Beatrice Richter, Jennifer Deppe, Anja Rahn, Dagmar-Christiane Fischer, Jörg Heineke, Dieter Haffner, Maren Leifheit-Nestler. FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis. International Journal of Molecular Sciences. 2019; 20 (18):4634.

Chicago/Turabian Style

Ineke Böckmann; Jonas Lischka; Beatrice Richter; Jennifer Deppe; Anja Rahn; Dagmar-Christiane Fischer; Jörg Heineke; Dieter Haffner; Maren Leifheit-Nestler. 2019. "FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis." International Journal of Molecular Sciences 20, no. 18: 4634.

Journal article
Published: 04 May 2019 in Journal of Neural Transmission
Reads 0
Downloads 0

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. Soluble α-Klotho (sKlotho) serum levels in patients with a major depressive episode and either undergoing electroconvulsive therapy (n = 16) or a monotherapy with an antidepressant (n = 37) were investigated. We measured the sKlotho serum levels in those patients before and after treatment and compared the baseline levels with those of age-matched healthy controls (n = 39). No group differences were found between the baseline sKlotho levels of patients and controls (573.5 pg/ml vs. 563.8 pg/ml; p = 0.80) and between pre- and post-treatment in the patients with depression (563.8 pg/ml vs. 561.8 pg/ml; p = 0.15), when treated either with electroconvulsive therapy or antidepressant. The major limitation of our study might be that peripheral material such as serum might not reliably reflect processes in the central nervous system. In sum, this first study on peripheral sKlotho levels in a clinical sample cannot confirm a global Klotho dysregulation in depression as it has been already suggested by others. Nonetheless, further preclinical and clinical studies on the involvement of Klotho in affective disorders should be carried out.

ACS Style

Alexander Sartorius; Maria Gilles; Anna-Maria Pfeifer; Michael Deuschle; Carolin Hoyer; Dieter Haffner; Maren Leifheit-Nestler; Laura Kranaster. Peripheral levels of the anti-aging hormone Klotho in patients with depression. Journal of Neural Transmission 2019, 126, 771 -776.

AMA Style

Alexander Sartorius, Maria Gilles, Anna-Maria Pfeifer, Michael Deuschle, Carolin Hoyer, Dieter Haffner, Maren Leifheit-Nestler, Laura Kranaster. Peripheral levels of the anti-aging hormone Klotho in patients with depression. Journal of Neural Transmission. 2019; 126 (6):771-776.

Chicago/Turabian Style

Alexander Sartorius; Maria Gilles; Anna-Maria Pfeifer; Michael Deuschle; Carolin Hoyer; Dieter Haffner; Maren Leifheit-Nestler; Laura Kranaster. 2019. "Peripheral levels of the anti-aging hormone Klotho in patients with depression." Journal of Neural Transmission 126, no. 6: 771-776.

Journal article
Published: 17 August 2018 in Neuropsychobiology
Reads 0
Downloads 0

Background: No candidate biomarkers based on cerebrospinal fluid (CSF) have been identified as prognostic factors in patients with major depression treated with electroconvulsive therapy (ECT), yet. Method: Following different underlying hypotheses, we analysed baseline CSF levels of markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system (interleukin [IL]-6, neopterin, soluble CD14, soluble CD163, migration inhibitory factor and monocyte chemotactic protein 1), endocannabinoids, sphingolipids and Klotho before ECT in patients with depression (n = 12) to identify possible correlations with the clinical antidepressant response to ECT. Results: Correlation with the reduction of the depressive symptoms could be observed especially for markers of neurodegeneration and elements of the innate immune system. Differences for CSF levels of several markers were found between the groups of responders and non-responders at the trend level. Limitations: The sample size is small and the ­distribution of responders and non-responders is uneven. Conclusions: It is this first study on CSF biomarkers for antidepressant efficacy of ECT warrants further research regarding the mechanism of ECT and personalized antidepressant therapy.

ACS Style

Laura Kranaster; Carolin Hoyer; Suna S. Aksay; J. Malte Bumb; Norbert Müller; Peter Zill; Markus J. Schwarz; Natalie Moll; Beat Lutz; Laura Bindila; Inga Zerr; Matthias Schmitz; Kaj Blennow; Henrik Zetterberg; Dieter Haffner; Maren Leifheit-Nestler; Cagakan Ozbalci; Christoph Janke; Manfred Thiel; Alexander Sartorius. Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study. Neuropsychobiology 2018, 77, 13 -22.

AMA Style

Laura Kranaster, Carolin Hoyer, Suna S. Aksay, J. Malte Bumb, Norbert Müller, Peter Zill, Markus J. Schwarz, Natalie Moll, Beat Lutz, Laura Bindila, Inga Zerr, Matthias Schmitz, Kaj Blennow, Henrik Zetterberg, Dieter Haffner, Maren Leifheit-Nestler, Cagakan Ozbalci, Christoph Janke, Manfred Thiel, Alexander Sartorius. Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study. Neuropsychobiology. 2018; 77 (1):13-22.

Chicago/Turabian Style

Laura Kranaster; Carolin Hoyer; Suna S. Aksay; J. Malte Bumb; Norbert Müller; Peter Zill; Markus J. Schwarz; Natalie Moll; Beat Lutz; Laura Bindila; Inga Zerr; Matthias Schmitz; Kaj Blennow; Henrik Zetterberg; Dieter Haffner; Maren Leifheit-Nestler; Cagakan Ozbalci; Christoph Janke; Manfred Thiel; Alexander Sartorius. 2018. "Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study." Neuropsychobiology 77, no. 1: 13-22.

Original research article
Published: 21 June 2018 in Frontiers in Endocrinology
Reads 0
Downloads 0

Clinical and experimental studies indicate a possible link between high serum levels of fibroblast growth factor 23 (FGF23), phosphate, and parathyroid hormone (PTH), deficiency of active vitamin D (1,25D) and klotho with the development of pathological cardiac remodeling, i.e., left ventricular hypertrophy and myocardial fibrosis, but a causal link has not been established so far. Here, we investigated the cardiac phenotype in klotho hypomorphic (kl/kl) mice and Hyp mice, two mouse models of elevated FGF23 levels and klotho deficiency, but differing in parameters of mineral metabolism, by using histology, quantitative real-time PCR, immunoblot analysis, and serum and urine biochemistry. Additionally, the specific impact of calcium, phosphate, PTH, and 1,25D on hypertrophic growth of isolated neonatal rat cardiac myocytes was investigated in vitro. Kl/kl mice displayed high serum Fgf23 levels, increased relative heart weight, enhanced cross-sectional area of individual cardiac myocytes, activated cardiac Fgf23/Fgf receptor (Fgfr) 4/calcineurin/nuclear factor of activated T cell (NFAT) signaling, and induction of pro-hypertrophic NFAT target genes including Rcan1, bMHC, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) as compared to corresponding wild-type (WT) mice. Investigation of fibrosis-related molecules characteristic for pathological cardiac remodeling processes demonstrated ERK1/2 activation and enhanced expression of Tgf-β1, collagen I, and Mmp2 in kl/kl mice than in WT mice. In contrast, despite significantly elevation of serum and cardiac Fgf23, and reduced renal klotho expression, Hyp mice showed no signs of pathological cardiac remodeling. Kl/kl mice showed enhanced serum calcium and phosphate levels, while Hyp mice showed unchanged serum calcium levels, lower serum phosphate, and elevated serum iPTH concentrations compared to corresponding WT mice. In cultured cardiac myocytes, treatment with both calcium or phosphate significantly upregulated endogenous Fgf23 mRNA expression and stimulated hypertrophic cell growth and expression of pro-hypertrophic genes. The treatment with PTH induced hypertrophic cell growth only, and stimulation with 1,25D had no significant effects. In conclusion, our data indicate that Hyp mice, in contrast to kl/kl mice appear to be protected from pathological cardiac remodeling during conditions of high FGF23 levels and klotho deficiency, which may be due, at least in part, to differences in mineral metabolism alterations, i.e., hypophosphatemia and lack of hypercalcemia.

ACS Style

Maren Leifheit-Nestler; Beatrice Richter; Melis Basaran; Julia Nespor; Isabel Vogt; Ioana Alesutan; Jakob Voelkl; Florian Lang; Joerg Heineke; Stefanie Krick; Dieter Haffner. Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23. Frontiers in Endocrinology 2018, 9, 333 .

AMA Style

Maren Leifheit-Nestler, Beatrice Richter, Melis Basaran, Julia Nespor, Isabel Vogt, Ioana Alesutan, Jakob Voelkl, Florian Lang, Joerg Heineke, Stefanie Krick, Dieter Haffner. Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23. Frontiers in Endocrinology. 2018; 9 ():333.

Chicago/Turabian Style

Maren Leifheit-Nestler; Beatrice Richter; Melis Basaran; Julia Nespor; Isabel Vogt; Ioana Alesutan; Jakob Voelkl; Florian Lang; Joerg Heineke; Stefanie Krick; Dieter Haffner. 2018. "Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23." Frontiers in Endocrinology 9, no. : 333.

Review article
Published: 28 May 2018 in Frontiers in Endocrinology
Reads 0
Downloads 0

Fibroblast growth factor (FGF) 23 is a phosphaturic hormone primarily secreted by osteocytes to maintain phosphate and mineral homeostasis. In patients with and without chronic kidney disease, enhanced circulating FGF23 levels associate with pathologic cardiac remodeling, i.e., left ventricular hypertrophy (LVH) and myocardial fibrosis and increased cardiovascular mortality. Experimental studies demonstrate that FGF23 promotes hypertrophic growth of cardiac myocytes via FGF receptor 4-dependent activation of phospholipase Cγ/calcineurin/nuclear factor of activated T cell signaling independent of its co-receptor klotho. Recent studies indicate that FGF23 is also expressed in the heart, and markedly enhanced in various clinical and experimental settings of cardiac remodeling and heart failure independent of preserved or reduced renal function. On a cellular level, FGF23 is expressed in cardiac myocytes and in other non-cardiac myocytes, including cardiac fibroblasts, vascular smooth muscle and endothelial cells in coronary arteries, and in inflammatory macrophages. Current data suggest that secreted by cardiac myocytes, FGF23 can stimulate pro-fibrotic factors in myocytes to induce fibrosis-related pathways in fibroblasts and consequently cardiac fibrosis in a paracrine manner. While acting on cardiac myocytes, FGF23 directly induces pro-hypertrophic genes and promotes the progression of LVH in an autocrine and paracrine fashion. Thus, enhanced FGF23 may promote cardiac injury in various clinical settings not only by endocrine but also via paracrine/autocrine mechanisms. In this review, we discuss recent clinical and experimental data regarding molecular mechanisms of FGF23’s paracrine action on the heart with respect to pathological cardiac remodeling.

ACS Style

Maren Leifheit-Nestler; Dieter Haffner. Paracrine Effects of FGF23 on the Heart. Frontiers in Endocrinology 2018, 9, 278 .

AMA Style

Maren Leifheit-Nestler, Dieter Haffner. Paracrine Effects of FGF23 on the Heart. Frontiers in Endocrinology. 2018; 9 ():278.

Chicago/Turabian Style

Maren Leifheit-Nestler; Dieter Haffner. 2018. "Paracrine Effects of FGF23 on the Heart." Frontiers in Endocrinology 9, no. : 278.

Journal article
Published: 22 May 2018 in Kidney and Blood Pressure Research
Reads 0
Downloads 0

Background/Aims: Whether the immunosuppressive regimen is associated with micro- and macro-vascular status in pediatric kidney transplant recipients (KTx) is unknown. Methods: We performed a cross-sectional, case-control study in 44 pediatric KTx patients on either everolimus (EVR) plus calcineurin inhibitor or standard treatment, i.e. mycophenolate mofetil plus calcineurin inhibitor. Measurement of carotid intima-media thickness (cIMT) via ultrasound, central pulse wave velocity (PWV) by a cuff-based oscillometric technique, and skin microvascular blood flow during local heating via laser-Doppler-fluximetry (LDF) served as marker of subclinical vascular disease. Serum concentrations of angiopoietin-1 and -2, fibroblast-growth factor 23 (FGF23) and soluble klotho were measured. Results: EVR-treated patients exhibited a similar degree of hypertension, increased cIMT, elevated pro-inflammatory angiopoietin-2, and diminished endothelial survival factor angiopoietin-1 compared to healthy children but presented with a twofold more reduced skin micro-vascular function compared to standard treatment (each p< 0.001). By contrast, PWV and soluble klotho levels were normal in both groups. Conclusion: Endothelial dysfunction seems more frequent in KTx patients on EVR-based immunosuppressive regimen compared to standard immunosuppression.

ACS Style

Stephan Ruben; Martin Kreuzer; Anja Büscher; Rainer Büscher; Julia Thumfart; Uwe Querfeld; Hagen Staude; Thurid Ahlenstiel-Grunow; Anette Melk; Dagmar-Christiane Fischer; Maren Leifheit-Nestler; Lars Pape; Dieter Haffner. Impaired Microcirculation in Children After Kidney Transplantation: Everolimus Versus Mycophenolate Based Immunosuppression Regimen. Kidney and Blood Pressure Research 2018, 43, 793 -806.

AMA Style

Stephan Ruben, Martin Kreuzer, Anja Büscher, Rainer Büscher, Julia Thumfart, Uwe Querfeld, Hagen Staude, Thurid Ahlenstiel-Grunow, Anette Melk, Dagmar-Christiane Fischer, Maren Leifheit-Nestler, Lars Pape, Dieter Haffner. Impaired Microcirculation in Children After Kidney Transplantation: Everolimus Versus Mycophenolate Based Immunosuppression Regimen. Kidney and Blood Pressure Research. 2018; 43 (3):793-806.

Chicago/Turabian Style

Stephan Ruben; Martin Kreuzer; Anja Büscher; Rainer Büscher; Julia Thumfart; Uwe Querfeld; Hagen Staude; Thurid Ahlenstiel-Grunow; Anette Melk; Dagmar-Christiane Fischer; Maren Leifheit-Nestler; Lars Pape; Dieter Haffner. 2018. "Impaired Microcirculation in Children After Kidney Transplantation: Everolimus Versus Mycophenolate Based Immunosuppression Regimen." Kidney and Blood Pressure Research 43, no. 3: 793-806.

Journal article
Published: 01 March 2018 in European Neuropsychopharmacology
Reads 0
Downloads 0

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5pg/ml vs. 991.3pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system-specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder.

ACS Style

Carolin Hoyer; Alexander Sartorius; Suna Su Aksay; Jan Malte Bumb; Christoph Janke; Manfred Thiel; Dieter Haffner; Maren Leifheit-Nestler; Laura Kranaster. Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression. European Neuropsychopharmacology 2018, 28, 428 -435.

AMA Style

Carolin Hoyer, Alexander Sartorius, Suna Su Aksay, Jan Malte Bumb, Christoph Janke, Manfred Thiel, Dieter Haffner, Maren Leifheit-Nestler, Laura Kranaster. Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression. European Neuropsychopharmacology. 2018; 28 (3):428-435.

Chicago/Turabian Style

Carolin Hoyer; Alexander Sartorius; Suna Su Aksay; Jan Malte Bumb; Christoph Janke; Manfred Thiel; Dieter Haffner; Maren Leifheit-Nestler; Laura Kranaster. 2018. "Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression." European Neuropsychopharmacology 28, no. 3: 428-435.

Multicenter study
Published: 21 February 2018 in Nephrology Dialysis Transplantation
Reads 0
Downloads 0

BackgroundWe investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD).MethodsIn all, 80 vitamin D–deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73 m2], and 40 with advanced CKD from the observational Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study (eGFR 24 mL/min/1.73 m2). In each study, vitamin D supplementation was started in 20 children and 20 matched children not receiving vitamin D served as controls. Measures were taken at baseline and after a median period of 8 months. Age- and gender-related standard deviation scores (SDSs) were calculated.ResultsBefore vitamin D supplementation, children in the ERGO study had normal FGF23 (median 0.31 SDS) and BAP (−0.10 SDS) but decreased Klotho and sclerostin (−0.77 and −1.04 SDS, respectively), whereas 4C patients had increased FGF23 (3.87 SDS), BAP (0.78 SDS) and sclerostin (0.76 SDS) but normal Klotho (−0.27 SDS) levels. Vitamin D supplementation further increased FGF23 in 4C but not in ERGO patients. Serum Klotho and sclerostin normalized with vitamin D supplementation in ERGO but remained unchanged in 4C patients. BAP levels were unchanged in all patients. In the total cohort, significant effects of vitamin D supplementation were noted for Klotho at eGFR 40–70 mL/min/1.73 m2.ConclusionsVitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD.

ACS Style

Christian Lerch; Rukshana Shroff; Mandy Wan; Lesley Rees; Helen Aitkenhead; Ipek Kaplan Bulut; Daniela Thurn; Aysun Karabay Bayazit; Anna Niemirska; Nur Canpolat; Ali Düzova; Karolis Azukaitis; Ebru Yilmaz; Fatos Yalcinkaya; Jerome Harambat; Aysel Kiyak; Harika Alpay; Sandra Habbig; Ariane Zaloszyc; Oguz Soylemezoglu; Cengiz Candan; Alejandra Rosales; Anette Melk; Uwe Querfeld; Maren Leifheit-Nestler; Anja Sander; Franz Schaefer; Dieter Haffner; G Cortina; K Arbeiter; J Dusek; B Ranchin; M Fischbach; A Zalosczyk; M Galiano; R Büscher; C Gimpel; M Kemper; A Doyon; E Wühl; M Pohl; S Wygoda; N Jeck; B Kranz; M Wigger; G Montini; F Lugani; S Testa; E Vidal; Maria Chiara Matteucci; S Picca; A Jankauskiene; A Zurowska; D Drodz; Marcin Tkaczyk; T Urasinski; Mieczyslaw Litwin; M Szczepanska; A Texeira; A Peco-Antic; B Bucher; G Laube; A Anarat; E Basin; Nilgun Cakar; Y Bilginer; H Erdogan; O Donmez; A Balat; Salim Çalışkan; M Civilibal; S Emre; G Ozcelik; S Mir; B Sözeri; O Yavascan; Y Tabel; P Ertan; A Prytula; J Bachetta; G Klaus; M Geßner; C P Schmitt; S Stabouli; G Reusz; Enrico Eugenio Verrina; J Groothoff; C Tondel; M A Gamero; E Petrosyan; S A Bakkaloglu; I Dursun; 4C study consortium; ESPN CKD-MBD working group. Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease. Nephrology Dialysis Transplantation 2018, 33, 2208 -2217.

AMA Style

Christian Lerch, Rukshana Shroff, Mandy Wan, Lesley Rees, Helen Aitkenhead, Ipek Kaplan Bulut, Daniela Thurn, Aysun Karabay Bayazit, Anna Niemirska, Nur Canpolat, Ali Düzova, Karolis Azukaitis, Ebru Yilmaz, Fatos Yalcinkaya, Jerome Harambat, Aysel Kiyak, Harika Alpay, Sandra Habbig, Ariane Zaloszyc, Oguz Soylemezoglu, Cengiz Candan, Alejandra Rosales, Anette Melk, Uwe Querfeld, Maren Leifheit-Nestler, Anja Sander, Franz Schaefer, Dieter Haffner, G Cortina, K Arbeiter, J Dusek, B Ranchin, M Fischbach, A Zalosczyk, M Galiano, R Büscher, C Gimpel, M Kemper, A Doyon, E Wühl, M Pohl, S Wygoda, N Jeck, B Kranz, M Wigger, G Montini, F Lugani, S Testa, E Vidal, Maria Chiara Matteucci, S Picca, A Jankauskiene, A Zurowska, D Drodz, Marcin Tkaczyk, T Urasinski, Mieczyslaw Litwin, M Szczepanska, A Texeira, A Peco-Antic, B Bucher, G Laube, A Anarat, E Basin, Nilgun Cakar, Y Bilginer, H Erdogan, O Donmez, A Balat, Salim Çalışkan, M Civilibal, S Emre, G Ozcelik, S Mir, B Sözeri, O Yavascan, Y Tabel, P Ertan, A Prytula, J Bachetta, G Klaus, M Geßner, C P Schmitt, S Stabouli, G Reusz, Enrico Eugenio Verrina, J Groothoff, C Tondel, M A Gamero, E Petrosyan, S A Bakkaloglu, I Dursun, 4C study consortium, ESPN CKD-MBD working group. Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease. Nephrology Dialysis Transplantation. 2018; 33 (12):2208-2217.

Chicago/Turabian Style

Christian Lerch; Rukshana Shroff; Mandy Wan; Lesley Rees; Helen Aitkenhead; Ipek Kaplan Bulut; Daniela Thurn; Aysun Karabay Bayazit; Anna Niemirska; Nur Canpolat; Ali Düzova; Karolis Azukaitis; Ebru Yilmaz; Fatos Yalcinkaya; Jerome Harambat; Aysel Kiyak; Harika Alpay; Sandra Habbig; Ariane Zaloszyc; Oguz Soylemezoglu; Cengiz Candan; Alejandra Rosales; Anette Melk; Uwe Querfeld; Maren Leifheit-Nestler; Anja Sander; Franz Schaefer; Dieter Haffner; G Cortina; K Arbeiter; J Dusek; B Ranchin; M Fischbach; A Zalosczyk; M Galiano; R Büscher; C Gimpel; M Kemper; A Doyon; E Wühl; M Pohl; S Wygoda; N Jeck; B Kranz; M Wigger; G Montini; F Lugani; S Testa; E Vidal; Maria Chiara Matteucci; S Picca; A Jankauskiene; A Zurowska; D Drodz; Marcin Tkaczyk; T Urasinski; Mieczyslaw Litwin; M Szczepanska; A Texeira; A Peco-Antic; B Bucher; G Laube; A Anarat; E Basin; Nilgun Cakar; Y Bilginer; H Erdogan; O Donmez; A Balat; Salim Çalışkan; M Civilibal; S Emre; G Ozcelik; S Mir; B Sözeri; O Yavascan; Y Tabel; P Ertan; A Prytula; J Bachetta; G Klaus; M Geßner; C P Schmitt; S Stabouli; G Reusz; Enrico Eugenio Verrina; J Groothoff; C Tondel; M A Gamero; E Petrosyan; S A Bakkaloglu; I Dursun; 4C study consortium; ESPN CKD-MBD working group. 2018. "Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease." Nephrology Dialysis Transplantation 33, no. 12: 2208-2217.

Journal article
Published: 07 February 2018 in Nephrology Dialysis Transplantation
Reads 0
Downloads 0
ACS Style

Maren Leifheit-Nestler; Felix Kirchhoff; Julia Nespor; Beatrice Richter; Birga Soetje; Michael Klintschar; Joerg Heineke; Dieter Haffner. Fibroblast growth factor 23 is induced by an activated renin–angiotensin–aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts. Nephrology Dialysis Transplantation 2018, 33, 1722 -1734.

AMA Style

Maren Leifheit-Nestler, Felix Kirchhoff, Julia Nespor, Beatrice Richter, Birga Soetje, Michael Klintschar, Joerg Heineke, Dieter Haffner. Fibroblast growth factor 23 is induced by an activated renin–angiotensin–aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts. Nephrology Dialysis Transplantation. 2018; 33 (10):1722-1734.

Chicago/Turabian Style

Maren Leifheit-Nestler; Felix Kirchhoff; Julia Nespor; Beatrice Richter; Birga Soetje; Michael Klintschar; Joerg Heineke; Dieter Haffner. 2018. "Fibroblast growth factor 23 is induced by an activated renin–angiotensin–aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts." Nephrology Dialysis Transplantation 33, no. 10: 1722-1734.

Comparative study
Published: 01 October 2017 in Bone
Reads 0
Downloads 0

X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)D (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health. Four-week-old male Hyp mice received R568 in different doses, 1,25D or vehicle for 28days. Vehicle-treated wild-type mice served as controls. Both R568 and 1,25D reduced PTH levels, yet only 1,25D raised serum phosphate levels in Hyp mice. 1,25D increased calciuria and further enhanced FGF23 synthesis in bone and circulating FGF23 levels. By contrast, R568 reduced bone FGF23 expression and serum total but not intact FGF23 concentrations. Renal 1,25D metabolism was further impaired by 1,25D and improved although not normalized by R568. Hyp mice showed reduced renal Klotho levels, which were increased by 1,25D and high dose R568. 1,25D, but not R568, significantly improved femur growth, and weight gain, and partially restored growth plate morphology and bone mineralization. Although a significant improvement of trabecular bone was noted by μCT, compared to 1,25D the effects of R568 on bone histomophometric parameters were marginal. Our data indicate that monotherapy with R568 reduced PTH and FGF23 synthesis in bone, but failed to restore vitamin D and phosphate metabolism and skeletal abnormalities in Hyp mice. By contrast, 1,25D improved body growth, and defective mineralization despite further enhancement of skeletal FGF23 synthesis thereby highlighting the importance of vitamin D in bone mineralization in Hyp mice.

ACS Style

Maren Leifheit-Nestler; Julia Kucka; Emi Yoshizawa; Geert Behets; Patrick D'Haese; Christian Bergen; Martin Meier; Dagmar-Christiane Fischer; Dieter Haffner. Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia. Bone 2017, 103, 224 -232.

AMA Style

Maren Leifheit-Nestler, Julia Kucka, Emi Yoshizawa, Geert Behets, Patrick D'Haese, Christian Bergen, Martin Meier, Dagmar-Christiane Fischer, Dieter Haffner. Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia. Bone. 2017; 103 ():224-232.

Chicago/Turabian Style

Maren Leifheit-Nestler; Julia Kucka; Emi Yoshizawa; Geert Behets; Patrick D'Haese; Christian Bergen; Martin Meier; Dagmar-Christiane Fischer; Dieter Haffner. 2017. "Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia." Bone 103, no. : 224-232.

Journal article
Published: 23 February 2017 in Nephrology Dialysis Transplantation
Reads 0
Downloads 0

Background. Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH.

ACS Style

Maren Leifheit-Nestler; Alexander Grabner; Laura Hermann; Beatrice Richter; Karin Schmitz; Dagmar-Christiane Fischer; Christopher Yanucil; Christian Faul; Dieter Haffner. Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats. Nephrology Dialysis Transplantation 2017, 32, 1493 -1503.

AMA Style

Maren Leifheit-Nestler, Alexander Grabner, Laura Hermann, Beatrice Richter, Karin Schmitz, Dagmar-Christiane Fischer, Christopher Yanucil, Christian Faul, Dieter Haffner. Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats. Nephrology Dialysis Transplantation. 2017; 32 (9):1493-1503.

Chicago/Turabian Style

Maren Leifheit-Nestler; Alexander Grabner; Laura Hermann; Beatrice Richter; Karin Schmitz; Dagmar-Christiane Fischer; Christopher Yanucil; Christian Faul; Dieter Haffner. 2017. "Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats." Nephrology Dialysis Transplantation 32, no. 9: 1493-1503.

Original article
Published: 08 February 2017 in Pediatric Nephrology
Reads 0
Downloads 0

Shiga-toxin-producing Escherichia coli (STEC)-associated hemolytic-uremic syndrome (HUS) is a major cause of acute kidney injury (AKI), especially in children. Its long-term outcome with respect to endothelial damage remains largely elusive. This was a cross-sectional study in 26 children who had suffered from STEC-HUS in the past and achieved a complete recovery of renal function (eGFR >90 ml/min/1.73 m2). Skin microcirculation after local heating was assessed by laser Doppler fluximetry, carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), 24-h ambulatory blood pressure, and angiopoietin (Ang) 1 and 2 serum levels after a median follow-up period of 6.1 years. The results were compared to those of healthy controls. All patients were normotensive, mean eGFR was 102 (range 91–154) ml/min/1.73 m2, and 13 of the 26 patients showed albuminuria. Endothelial dysfunction was present in 13 patients, and the mean serum Ang2/Ang1 ratio was increased compared to healthy children (each p < 0.05). In contrast, mean values for PWV and cIMT in the patients did not differ from those of the controls. Endothelial dysfunction was significantly associated with younger age at STEC-HUS manifestation, time after HUS, and presence of albuminuria. The results of this study highlight the need for long-term follow-up of STEC-HUS patients even after complete recovery of eGFR and lack of hypertension with respect to microvascular damage.

ACS Style

Martin Kreuzer; Laura Sollmann; Stephan Ruben; Maren Leifheit-Nestler; Dagmar-Christiane Fischer; Lars Pape; Dieter Haffner. Endothelial dysfunction during long-term follow-up in children with STEC hemolytic-uremic syndrome. Pediatric Nephrology 2017, 32, 1005 -1011.

AMA Style

Martin Kreuzer, Laura Sollmann, Stephan Ruben, Maren Leifheit-Nestler, Dagmar-Christiane Fischer, Lars Pape, Dieter Haffner. Endothelial dysfunction during long-term follow-up in children with STEC hemolytic-uremic syndrome. Pediatric Nephrology. 2017; 32 (6):1005-1011.

Chicago/Turabian Style

Martin Kreuzer; Laura Sollmann; Stephan Ruben; Maren Leifheit-Nestler; Dagmar-Christiane Fischer; Lars Pape; Dieter Haffner. 2017. "Endothelial dysfunction during long-term follow-up in children with STEC hemolytic-uremic syndrome." Pediatric Nephrology 32, no. 6: 1005-1011.