Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Stephanie Krämer is active.

Publication


Featured researches published by Stephanie Krämer.


American Journal of Physiology-renal Physiology | 2008

Increased mast cell number in human hypertensive nephropathy

Pia Welker; Stephanie Krämer; David A. Groneberg; Hans H. Neumayer; S. Bachmann; Kerstin Amann; Harm Peters

Mast cells have recently been related to nonallergic chronic organ damage and fibrosis. In the present study, we analyzed mast cell number, localization, and maturation in the kidney of a relatively unique group of middle-aged accident victims with primary essential hypertension and in normotensive controls (n=8 per group, Caucasians, predominantly male). Hypertensive kidneys showed a significantly higher degree of arteriolosclerosis. However, glomerular and tubulointerstitial matrix accumulation did not differ significantly to normotensive controls indicating a relatively early stage of hypertensive nephropathy. Using toluidine blue staining, renal mast cell number was found to be fivefold higher in hypertensive subjects compared with normotensive controls. Mast cells were primarily located in the peritubular interstitial spaces, some perivascular, but not in glomeruli. In a series of immunohistological staining studies, mast cell maturation grading showed that expression of early hematopoietic precursor cell marker CD34 did not differ between both groups. In contrast, mast cells were mostly positive for IgE receptor, tryptase, and chymase indicating a mature, differentiated cell phenotype in hypertensive nephropathy. Renal expression of stem cell factor was markedly upregulated in primary hypertension. Kidney macrophage and lymphocyte numbers were similar in both groups. In conclusion, human hypertensive kidney disease shows an early and conspicuous upregulation of stem cell factor along with an increased number of mature mast cells. The results suggest that renal mast cell accumulation may play a role in the pathogenesis of human hypertensive nephropathy.


Journal of Hypertension | 2012

Submaximal suppression of parathyroid hormone ameliorates calcitriol-induced aortic calcification and remodeling and myocardial fibrosis in uremic rats.

Susanne Jung; Uwe Querfeld; Dominik Müller; Birgit Rudolph; Harm Peters; Stephanie Krämer

Background and objective: In subtotally nephrectomized rats, we studied to what extent high-dose calcitriol-induced cardiovascular disease can be modulated by almost complete suppression of parathyroid hormone (PTH), mediated by either cinacalcet (CINA) or parathyroidectomy (PTX). Methods: Five groups were studied: sham-operated controls, uremic (U), uremic with calcitriol (U+1,25D), uremic and calcitriol with CINA (U+1,25D+CINA) and uremic and calcitriol with PTX (U+1,25D+PTX). Treatments lasted 14 weeks. Results: Compared with U group animals, PTH was significantly lower with calcitriol treatment and almost completely suppressed in animals treated with either PTX or CINA. Serum calcium and phosphorus levels were similarly elevated in all groups receiving calcitriol. Renal function in uremic animals was significantly more impaired in the U+1,25D group. Aortic calcifications were pronounced in U+1,25D animals and reduced by more than 50% by concomittant treatment with CINA or PTX. Chondrocytes were observed near areas of calcification (>90%) and endochondral bone formation was confirmed by positive immunofluorescence for chondrocytic transcription factor sox9 and matrix protein collagen X. Altered arterial (aneurysmatic) geometry with a significant increase in wall/lumen and lumen/body weight ratio was found only in the U+1,25D group. Myocardial fibrosis was present in all uremic groups with a significant increase in the U+1,25D group. Connective tissue growth factor messenger RNA was significantly upregulated only in the U+1,25D group. Conclusion: Submaximal suppression of PTH by either CINA or PTX reduced vascular calcifications, arterial remodeling and myocardial fibrosis to a similar degree and independent of the serum calcium and phosphorus levels. These data do not indicate vasculotropic effects of calcimimetics independent of PTH suppression.


Journal of Molecular Medicine | 2013

mTOR and regulation of energy homeostasis in humans

Marwan Mannaa; Stephanie Krämer; Michael Boschmann; Maik Gollasch

Patients treated with the mammalian or mechanistic target of rapamycin (mTOR) inhibitor everolimus in order to slow progression of autosomal-dominant polycystic kidney disease (ADPKD) showed a significant reduction of body weight. Although the detailed mechanism of how mTOR inhibition interferes with body weight regulation is rather unclear, present data suggest that this effect is mediated by both central and peripheral mechanisms. These findings in ADPKD patients are in contrast to well-documented effects of hypothalamic mTOR on regulation of energy homeostasis and eating behavior in rodents. In a number of rodent models, the mTOR inhibitor rapamycin induces increased food intake, which is accompanied by increased body weight. However, animal data are inconsistent. This review highlights some of the regulatory signals and key mechanisms that are important for balancing energy intake and energy expenditure with a special focus on adipose tissue-derived adipokines and their interaction with mTOR regarding local regulation of tissue perfusion and metabolism and overall systemic energy homeostasis. Specifically, clinical aspects of an impaired mTOR signaling pathway regarding the development of obesity and type-2 diabetes mellitus will be discussed.


American Journal of Physiology-renal Physiology | 2008

Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative glomerulosclerosis

Stephanie Krämer; Susanne Kron; Yingrui Wang-Rosenke; Tanja Loof; Dmytro Khadzhynov; Stanislao Morgera; Hiroshi Kawachi; Fujio Shimizu; Sebastian Martini; Hans-H. Neumayer; Harm Peters

Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative glomerulosclerosis (GS). Progressive mesangioproliferative glomerulonephritis, mostly IgA nephropathy, is a major cause of end-stage kidney disease worldwide. In a chronic-progressive model of mesangioproliferative GS, we tested the renoprotective efficacy of rosuvastatin alone and in combination with a high-dose of the AT(1) blocker candesartan. Treatment was started 1 wk after disease induction (anti-thy1 antibody injection into uninephrectomized rats) and continued until week 20. Tubulointerstitial expression of the key fibrosis mediator transforming growth factor (TGF)-beta served as the main marker of disease progression. Compared with the untreated GS rats (475 +/- 52 pg/ml), tubulointerstitial TGF-beta(1) protein expression was significantly reduced by both single therapies (rosuvastatin -47%, candesartan -51%, P < 0.01). Tubulointerstitial matrix accumulation (matrix score in GS: 64 +/- 7%) was relatively reduced by -45 and -52%, respectively (P < 0.01). The combination of rosuvastatin and candesartan had significantly greater effects on tubulointerstitial TGF-beta(1) expression (-82% vs. GS) and matrix accumulation (-83% vs. GS) (P < 0.001 vs. GS, P < 0.05 vs. single therapy) than either drug alone. Similar additive beneficial effects were observed for renal fibronectin and tissue inhibitor of metalloproteinase-1 expression, cell proliferation, macrophage infiltration, proteinuria, and kidney function. In conclusion, rosuvastatin limits the progressive course of anti-thy1-induced GS toward chronic tubulointerstitial fibrosis and renal insufficiency to a degree comparable to the one achieved by a high dose of the AT(1) antagonist candesartan. Combined treatment yields significantly greater actions on renal TGF-beta overexpression and matrix accumulation, cell proliferation, and macrophage infiltration. The results suggest that rosuvastatin and an AT(1) blocker independently interfere with separate key pathways involved in the progression of chronic mesangioproliferative GS.


American Journal of Physiology-renal Physiology | 2008

Magnesium stimulates renal phosphate reabsorption

Julia Thumfart; Susanne Jung; Salah Amasheh; Stephanie Krämer; Harm Peters; Kerstin Sommer; Jiirg Biber; Heini Murer; Iwan C. Meij; Uwe Querfeld; Carsten A. Wagner; Dominik Müller

In the kidney, approximately 80% of the filtered phosphate (Pi) is reabsorbed along the proximal tubule. Changes in renal Pi reabsorption are associated with modulation of the sodium-dependent Pi cotransporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) protein abundance in the brush-border membrane (BBM) of proximal tubule cells. NaPi-IIa is mainly regulated by dietary Pi intake and parathyroid hormone (PTH). The purpose of the present study was to elucidate the effect of alteration in dietary magnesium (Mg2+) intake on renal Pi handling. Urinary Pi excretion and renal expression of NaPi-IIa and NaPi-IIc were analyzed in rats fed a normal (0.2%) or high-Mg2+ (2.5%) diet. A high-Mg2+ diet resulted in decreased renal Pi excretion and increased protein expression of NaPi-IIa and NaPi-IIc. Serum FGF-23 (fibroblast growth factor 23) levels were unchanged under a high-Mg2+ diet. Serum PTH levels were slightly decreased under a high-Mg2+ diet. To examine whether the observed changes in renal Pi reabsorption are PTH dependent, expression of NaPi-IIa and NaPi-IIc was also analyzed in parathyroidectomized (PTX) rats fed a normal or high-Mg2+ diet. In PTX rats, Mg2+ had no significant effect on renal Pi excretion or NaPi-IIa protein expression. Mg2+ increased NaPi-IIc protein expression in PTX rats. This experiment shows for the first time on the molecular level how Mg2+ stimulates renal Pi reabsorption. Under a high-Mg2+ diet, NaPi-IIa expression is dependent on PTH levels, whereas NaPi-IIc expression seems to be independent of PTH levels.


Scientific Reports | 2016

Role of cystathionine gamma-lyase in immediate renal impairment and inflammatory response in acute ischemic kidney injury

Lajos Markó; István András Szijártó; Milos R. Filipovic; Mario Kaßmann; András Balogh; Joon Keun Park; Lukasz Przybyl; Gabriele N'Diaye; Stephanie Krämer; Juliane Anders; Isao Ishii; Dominik N. Müller; Maik Gollasch

Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth−/− and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth−/− mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth−/− mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection.


Acta Physiologica | 2017

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2.

Lajos Markó; Marwan Mannaa; T. N. Haschler; Stephanie Krämer; Maik Gollasch

Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca2+ influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS). TRP vanilloid 4 receptor channels (TRPV4) are highly expressed in the kidney, where they induce Ca2+ influx into endothelial and tubular cells. TRP melastatin (TRPM2) non‐selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology. Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown. In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.


Journal of Hypertension | 2015

Soluble guanylate cyclase stimulator BAY 41-8543 and female sex ameliorate uremic aortic remodeling in a rat model of mild uremia.

Bianca Stancu; Stephanie Krämer; Tanja Loof; Alice Mika; Kerstin Amann; Hans-H. Neumayer; Harm Peters

Background: Cardiovascular disease is the leading comorbidity in renal patients and has been related to impaired nitric oxide signaling. Estrogens exert protective effects on the vascular system. This study investigates the effects of biological sex and nitric oxide-independent soluble guanylate cyclase (sGC) stimulator BAY 41-8543 on aortic remodeling in experimental mild uremia. Method: Age-matched male and female Wistar rats were assigned for 18 weeks into sham-operated, subtotally nephrectomized (SNX), SNX + BAY 41-8543 and SNX + hydralazine. Analysis involved functional, histological, and molecular kidney and thoracic aorta parameters. Results: SNX significantly increased SBP, which was comparably reduced to control levels by BAY 41-8543 and hydralazine. In SNX males, uremic aortic remodeling was characterized by marked media thickening and increased media-to-lumen ratio (P < 0.01), vascular smooth muscle cell (VSMC) proliferation, macrophage infiltration, extracellular matrix turnover, decreased aortic elastin-to-collagen ratio (P < 0.01) and endothelial nitric oxide-synthase (eNOS) mRNA expression (P < 0.05). No significant alterations of aortic media-to-lumen ratio, VSMC proliferation, macrophage infiltration, matrix metalloproteinase-2, and eNOS mRNA expressions were seen in female uremic animals. BAY 41-8543 significantly ameliorated uremic aortic remodeling and stiffening involving reduced VSMC proliferation, collagen I-deposition, extracellular matrix turnover, and increased elastin content and eNOS mRNA expression. Hydralazine treatment did not substantially alter aortic remodeling. Conclusion: Experimental mild uremia leads to pronounced aortic hypertrophic remodeling and stiffening with sex-dependent alternations, and these are more severe in male rats. BAY 41-8543 ameliorates uremic aortic remodeling in a blood pressure-independent manner. The results suggest that sGC-stimulators may offer a novel treatment mode for pathological arterial wall remodeling in patients with impaired renal function.


Transplantation | 2010

Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice

Hong Zebger-Gong; Jan Kampmann; Linghua Kong; J. Roigas; Kerstin Sommer; Uwe Hoff; Stephanie Krämer; Harm Peters; Dominik Müller; Duska Dragun; Uwe Querfeld

Background. Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection. Methods. The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (−/−) for a knockout of the eNOS gene (eNOS−/−). Results. After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS−/− recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS. Conclusions. Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.


BMC Pharmacology | 2005

Enhancing cGMP in anti-thy1-induced, chronic-progressive glomerulosclerosis: sGC stimulation versus PDEs inhibition

Yingrui Wang; Stephanie Krämer; Tanja Loof; Sebastian Martini; Susanne Kron; Hiroshi Kawachi; Fuijo Shimizu; Hans-H. Neumayer; Harm Peters

Results Compared to normal controls, sGC mRNA expression (alpha1 sGC +260% and beta1 sGC +310%) and NOstimulated cGMP production (+270%) were up-regulated in the tubulointerstitium of the untreated cGS animals, while its activity was depressed in glomeruli (-50%). As compared to untreated the cGS group, Bay 41-2272 treatment significantly enhanced glomerular and tubulointerstitial NO-cGMP (+92% and +88%) signaling. This went along with markedly reduced glomerular and tubulointerstitial macrophage infiltration (-42% and -50%), number of proliferating cells (-31% and -30%), matrix protein expression (TGF-β protein -36% and -50%) and accumulation (histological matrix score -47% and -42%) as well as improved kidney function (plasma creatinine -57%). In contrast, PTX therapy only moderately, but not significantly affected the above parameters.

Collaboration


Dive into the Stephanie Krämer's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Sebastian Martini

Humboldt University of Berlin

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Yingrui Wang

Humboldt University of Berlin

View shared research outputs
Top Co-Authors

Avatar

Susanne Kron

Humboldt University of Berlin

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge