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Dive into the research topics where Eva Schrezenmeier is active.

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Featured researches published by Eva Schrezenmeier.


Acta Physiologica | 2017

Biomarkers in acute kidney injury – pathophysiological basis and clinical performance

Eva Schrezenmeier; Jonathan Barasch; Klemens Budde; T. Westhoff; Kai M. Schmidt-Ott

Various biomarkers of acute kidney injury (AKI) have been discovered and characterized in the recent past. These molecules can be detected in urine or blood and signify structural damage to the kidney. Clinically, they are proposed as adjunct diagnostics to serum creatinine and urinary output to improve the early detection, differential diagnosis and prognostic assessment of AKI. The most obvious requirements for a biomarker include its reflection of the underlying pathophysiology of the disease. Hence, a biomarker of AKI should derive from the injured kidney and reflect a molecular process intimately connected with tissue injury. Here, we provide an overview of the basic pathophysiology, the cellular sources and the clinical performance of the most important currently proposed biomarkers of AKI: neutrophil gelatinase‐associated lipocalin (NGAL), kidney injury molecule‐1 (KIM‐1), liver‐type fatty acid‐binding protein (L‐FABP), interleukin‐18 (IL‐18), insulin‐like growth factor‐binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP‐2) and calprotectin (S100A8/9). We also acknowledge each biomarkers advantages and disadvantages as well as important knowledge gaps and perspectives for future studies.


Biochemical Pharmacology | 2012

The (pro)renin receptor ((P)RR) can act as a repressor of Wnt signalling

Sarah Bernhard; Kerstin Seidel; Jennifer Schmitz; Sabrina Klare; Sebastian Kirsch; Eva Schrezenmeier; Daniela Zaade; Heike Meyborg; Petra Goldin-Lang; Philipp Stawowy; Frank S. Zollmann; Thomas Unger; Heiko Funke-Kaiser

The (pro)renin receptor ((P)RR) and Wnt signalling are both involved in different diseases ranging from cardiac and renal end-organ damage to cancer. (P)RR function involves signalling via the transcription factor promyelocytic leukemia zinc finger protein (PLZF) as well as the furin-mediated generation of vacuolar proton-translocating ATPase (V-ATPase)-associated and soluble (P)RR isoforms. Recently, the (P)RR was described as adaptor protein of Wnt (co)receptors. The aim of this study was to analyse the contribution of these distinct (P)RR functions to Wnt signalling. Using Tcf/Lef reporter gene systems in HEK293T and HepG2 cells and quantification of endogenous axin2 mRNA and protein levels in HEK293T cells we were able to demonstrate that full-length (P)RR acts as a repressor of Wnt signalling in a system preactivated either by Wnt3a stimulation or by constitutively active β-catenin. These repressive effects are mediated by Dvl but are independent of the mutation status of β-catenin. Furthermore, the V-ATPase complex, but not PLZF translocation or renin enzymatic activity, is necessary for the induction of Tcf/Lef-responsive genes by Wnt3a. Our data indicate interference of (P)RR and Wnt cascades, a fact that has to be considered concerning pathophysiology of cardio-renal and oncological entities as well as in drug development programs targeting (P)RR or Wnt pathways.


American Journal of Transplantation | 2017

Successful Recovery of Acute Renal Transplant Failure in Recurrent Hepatitis C Virus–Associated Membranoproliferative Glomerulonephritis

Eva Schrezenmeier; Kayin Wu; Fabian Halleck; Lutz Liefeldt; Susanne Brakemeier; Friederike Bachmann; Susanne Kron; Klemens Budde; Michael Duerr

Recurrence of hepatitis C virus (HCV)–associated membranoproliferative glomerulonephritis (MPGN) in the kidney transplant may lead to continuous graft deterioration and the need for further renal replacement therapy. The novel direct‐acting antiviral agents (DAAs) allow a highly effective and interferon‐free treatment option for chronic HCV‐infected patients. Data on the therapeutic safety and efficacy in HCV‐infected renal transplant patients are sparse, especially for patients with severe renal impairment. We report the case of a 63‐year‐old female HCV‐positive renal transplant patient with biopsy‐proven recurrence of MPGN in the renal graft 3 years after transplant. Because of rapid loss of transplant function and consecutive need for hemodialysis, we initiated a combined anti‐HCV–directed therapy regimen consisting of daclatasvir and simeprevir over 12 weeks. Viral clearance of HCV was obtained as early as 2 weeks after start of treatment. No adverse therapy‐associated side effects were observed, and immunosuppressive dosing remained unchanged. Importantly, graft function fully recovered and hemodialysis was stopped 2 mo after the end of daclatasvir/simeprevir treatment. We report the first case of successful recovery of dialysis‐dependent renal transplant failure after treatment of recurrent HCV‐associated MPGN in a kidney transplant recipient by curing the underlying HCV infection with a combination of novel DAAs.


International Journal of Molecular Medicine | 2014

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

Sebastian Kirsch; Eva Schrezenmeier; Sabrina Klare; Daniela Zaade; Kerstin Seidel; Jennifer Schmitz; Sarah Bernhard; Dilyara Lauer; Mark Slack; Petra Goldin-Lang; Thomas Unger; Frank S. Zollmann; Heiko Funke-Kaiser

The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. The distinct molecular mechanisms of this receptor are still incompletely understood. The (P)RR is able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains of the (P)RR are essential for V-ATPase activity. V-ATPase- and Wnt-mediated effects imply constitutive, i.e., (pro)renin-independent functions of the (P)RR. Regarding ligand-dependent (P)RR signalling, the role of prorenin glycosylation is currently unknown. Therefore, the aim of this study was to analyse the contribution of constitutive (P)RR activity to its cellular effects and the relevance of prorenin glycosylation on its ligand activity. We were able to demonstrate that high glucose induces (P)RR signal transduction whereas deglycosylation of prorenin abolishes its intrinsic activity in neuronal and epithelial cells. By using siRNA against (P)RR or PLZF as well as the PLZF translocation blocker genistein and the specific V-ATPase inhibitor bafilomycin, we were able to dissect three distinct sub-pathways downstream of the (P)RR. The V-ATPase function is ligand-independently associated with strong pro-proliferative effects whereas prorenin causes moderate proliferation in vitro. In contrast, PLZF per se [i.e., in the absence of (pro)renin] does not interfere with cell number.


Kidney International Reports | 2016

Urinary NGAL-Positive Acute Kidney Injury and Poor Long-term Outcomes in Hospitalized Patients

Eugenia Singer; Eva Schrezenmeier; Antje Elger; Evelyn Seelow; Alexander Krannich; Friedrich C. Luft; Kai M. Schmidt-Ott

Introduction Neutrophil gelatinase−associated lipocalin (NGAL) is a widely studied biomarker of renal tubular injury. Urinary NGAL (uNGAL) during acute kidney injury (AKI) predicts short-term adverse outcomes. However, the long-term predictive value is unknown. Methods We performed a prospective observational study of 145 patients with hospital-acquired AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria and analyzed the long-term predictive value of uNGAL at the time of AKI. We defined a composite outcome of all-cause mortality and the development of end-stage renal disease (ESRD). Results In all, 61 AKI patients died and 22 developed ESRD within 6 months. The uNGAL levels were significantly higher in patients with poor long-term outcomes. uNGAL levels ≥362 μg/l (highest quartile) and uNGAL levels between 95 and 362 μg/l (third quartile) were associated with hazard ratios of 3.7 (95% confidence interval, 2.1–6.5) and 1.9 (1.1–3.5), respectively, compared with uNGAL levels <95 μg/l (lower quartiles). After 6 months, 67% and 43% of patients within the highest and third uNGAL quartile, respectively, had either progressed to ESRD or died, compared to only 21% of patients with uNGAL in the lower 2 quartiles (P < 0.001). In multivariable Cox regression analyses accounting for conventional predictors, uNGAL was the strongest independent predictor of adverse long-term outcomes. The association of uNGAL levels and poor long-term outcomes remained significant in the subgroup of 107 AKI survivors discharged without requiring dialysis (P = 0.002). Discussion These data indicate that elevated uNGAL levels at AKI diagnosis predict poor long-term outcomes.


Pharmacology | 2012

Moderate Correlations of in vitro versus in vivo Pharmacokinetics Questioning the Need of Early Microsomal Stability Testing

Eva Schrezenmeier; Frank S. Zollmann; Kerstin Seidel; Christian Böhm; Kristin Schmerbach; Melanie Kroh; Sebastian Kirsch; Sabrina Klare; Sarah Bernhard; Kai Kappert; Petra Goldin-Lang; Werner Skuballa; Thomas Unger; Heiko Funke-Kaiser

Background/Aims: Putative in vitro-in vivo correlations of pharmacokinetic (PK) parameters are regarded as a prerequisite to filter hits derived from high-throughput screening (HTS) approaches for subsequent murine in vivo PK studies. Methods: In this study, we assessed stabilities in rat and human microsomes of 121 compounds from an early, academic drug discovery programme targeting the (pro)renin receptor and correlated the respective data with single-dose, in vivo PK parameters of 22 hits administered intravenously in rats. Results: After transformation of in vitro half-lives to predicted in vivo hepatic clearances, r2 regarding in vitro-in vivo clearance correlations were 0.31 and 0.27 for the rat and human species, respectively. Conclusions: Our data concerning structurally diverse real-world compounds indicate that microsomal stability testing is not a tool to triage early compounds for in vivo PK testing.


Nephrology Dialysis Transplantation | 2018

Assessment of the Kidney Donor Profile Index in a European cohort

Lukas Lehner; Anna Kleinsteuber; Fabian Halleck; Dmytro Khadzhynov; Eva Schrezenmeier; Michael Duerr; Kai-Uwe Eckardt; Klemens Budde; Oliver Staeck

Background Recently, transplant societies have had to change their allocation policies to counter global organ shortages. However, strategies differ significantly and long-term outcomes and cross-regional applicability remain to be evaluated. Methods Therefore, we retrospectively analysed the Kidney Donor Profile Index (KDPI) of 987 adult kidney transplants at our centre using data from the Organ Procurement and Transplantation Network (OPTN) as a reference. Results In our cohort, the median KDPI was 66%, with a higher proportion of >85% KDPI kidneys compared with the US cohort (32.3% versus 9.2%). Among elderly patients (≥65 years of age), 62% received >95% KDPI kidneys, which were primarily allocated within the Eurotransplant Senior Program (ESP). After 10 years, the rate of death-censored graft survival was 70.5%. Recipients of >85% KDPI kidneys were significantly older, demonstrating higher mortality, poorer graft survival and lower estimated glomerular filtration rate. Patients receiving ≥99% KDPI kidneys had a satisfactory 5-year death-censored graft survival (72.9%). The 5-year survival rate of patients living with a functioning graft exceeded the matched OPTN data in the whole KDPI range, despite a higher proportion of elderly recipients. Multivariate analysis revealed KDPI as an independent risk factor for graft loss (hazard ratio 1.14/10%, P < 0.001), although C-statistics of 0.62 indicated limited discriminative ability for individuals. Conclusion The analysis demonstrated KDPI as a potentially useful tool for donor quality assessment in a European cohort. Most importantly, our analysis revealed acceptable outcomes even for very high KDPI kidneys.


Transplantation Proceedings | 2017

Incidence of Infectious Disease and Malignancies After Rituximab Therapy in Kidney Transplant Recipients: Results From a Cohort in Germany

Eva Schrezenmeier; Klemens Budde; Oliver Staeck; Lukas Lehner; Michael Duerr; Dmytro Khadzhynov; T. Dörner; Fabian Halleck

BACKGROUND Rituximab is frequently used in solid organ transplantation off-label, especially in patients with renal allografts. Few data are available on the safety aspects of solid organ transplant recipients receiving rituximab. There is a knowledge gap on long-term follow-up data, in particular on infectious complications. PATIENTS AND METHODS A retrospective observational registry study (German Registry on Autoimmune Diseases) comprising a total of 681 patients was conducted. The data of 63 adult kidney transplant recipients who received rituximab between 2006 and 2013 were used in this analysis. RESULTS Median follow-up was 42 (1-109) months. At least 1 severe infection occurred in 57% of patients. The median time between the first rituximab infusion and the first infection was 4 (1-48) months. Of the overall 88 infections, 74 were severe bacterial infections, 5 were severe viral infections, 3 were severe fungal infections, 2 were combined severe bacterial and fungal infections, and 4 were combined severe viral, fungal and bacterial infections. Seven patients died during the observational period, 2 of them due to infectious complications. In the observational period, 1 case of squamous cell carcinoma but no other malignancies were observed. CONCLUSION Consistent with previous data, a high incidence of infections was observed after rituximab treatment in kidney transplant recipients. Most infections occurred within 6 months after rituximab initiation. With more than 3 years of follow-up, we were able to document a low incidence of secondary malignancies after rituximab with only 1 case in our cohort.


Nephrology Dialysis Transplantation | 2016

Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching?

Fabian Halleck; Dmytro Khadzhynov; Lutz Liefeldt; Eva Schrezenmeier; Lukas Lehner; Michael Duerr; Danilo Schmidt; Jamal Bamoulid; Nils Lachmann; Johannes Waiser; Klemens Budde; Oliver Staeck


Nephrology Dialysis Transplantation | 2018

SP747SUCCESSFUL HCV THERAPY WITH NOVEL DAA REGIMEN IMPROVES GLUCOSE TOLERANCE AND MAY PREVENT POST-TRANSPLANT DIABETES MELLITUS IN RENAL TRANSPLANT RECIPIENTS

Leon Bergfeld; Eva Schrezenmeier; Lukas Lehner; Oliver Staeck; Dmytro Khadzhynov; Kai-Uwe Eckardt; Klemens Budde; Fabian Halleck; Michael Duerr

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