A5083723682- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Adenosine and Purinergic Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Dialysis and Renal Disease Management
- Diabetes Treatment and Management
- Acute Kidney Injury Research
- Nitric Oxide and Endothelin Effects
- Blood groups and transfusion
- Blood Pressure and Hypertension Studies
- Renal Transplantation Outcomes and Treatments
- Escherichia coli research studies
- Immune Cell Function and Interaction
- Erythropoietin and Anemia Treatment
- Hemoglobinopathies and Related Disorders
- Neurological Complications and Syndromes
- Ion Transport and Channel Regulation
- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
- Platelet Disorders and Treatments
- Organ Transplantation Techniques and Outcomes
- Iron Metabolism and Disorders
- Diabetes Management and Research
- Pregnancy and preeclampsia studies
Klinikum Region Hannover
2021-2024
University of Oxford
2023
Klinikum Bremen-Mitte
2023
Medizinische Hochschule Hannover
2013-2022
Hypertension Institute
2014
PhenoSystems (Belgium)
2008
Max Delbrück Center
2003
Charité - Universitätsmedizin Berlin
2003
Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component caveolae, we generated mice lacked caveolae. The absence this organelle impaired nitric oxide calcium signaling cardiovascular system, causing aberrations endothelium-dependent relaxation, contractility, maintenance myogenic tone. In addition, lungs knockout animals...
Atypical hemolytic–uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels hematologic measures but does not treat the underlying systemic disease.
<b>Objective</b> To evaluate the effect of different treatment strategies on enterohaemorrhagic <i>Escherichia coli</i> O104:H4 induced haemolytic uraemic syndrome. <b>Design</b> Multicentre retrospective case-control study. <b>Setting</b> 23 hospitals in northern Germany. <b>Participants</b> 298 adults with <i>E <b>Main outcome measures</b> Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation bowel or necrosis, and death. <b>Results</b> 160 patients (54%)...
Atypical hemolytic uremic syndrome (aHUS) is a rare genetic life-threatening disease of chronic uncontrolled complement activation leading to thrombotic microangiopathy (TMA) and severe end-organ damage. Eculizumab, terminal inhibitor approved for aHUS treatment, was reported improve hematologic renal parameters in 2 prior prospective phase studies. This the largest study eculizumab date, conducted an adult population.Open-label single-arm trial.Patients 18 years or older with (platelet...
Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults atypical hemolytic uremic syndrome presenting thrombotic microangiopathy. In this global, phase 3, single arm study complement inhibitor-naïve (18 years older) who fulfilled diagnostic criteria for syndrome, enrolled patients received through 26-week initial...
The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested hypothesis low-dose therapy with long-acting recombinant human analogue darbepoetin alpha protects vascular endothelium vivo a classic remnant kidney rat model characterized by severe damage, progressive sclerosis, and ischemia-induced tissue fibrosis.Using parallel group study design,...
There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of aHUS treated eculizumab.Patients who participated any five parent eculizumab trials and received at least one infusion were eligible for enrollment a follow-up study. Rates thrombotic microangiopathy (TMA) manifestations off versus on evaluated. Additional endpoints included change...
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for treatment of adults experiencing an acute episode aTTP, in conjunction with plasma exchange (PEX) and immunosuppression minimum 30 days after stopping daily PEX. We performed retrospective, observational analysis on use 60 patients from 29 medical centers Germany during disease management. Caplacizumab led to rapid normalization platelet count...
Complement activation plays a key role in mediating apoptosis, inflammation, and transplant rejection. In this study, the of complement 5a receptor (C5aR) was examined human renal allografts an allogenic mouse model kidney transplants with acute rejection, C5aR expression increased tissue cells infiltrating tubulointerstitium. Similar findings were observed mice. When recipient mice treated once daily antagonist before transplantation, long-term allograft survival markedly improved compared...
Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated increased mortality risk cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated prognostic role mtDNA cause-specific 4812 patients from German Kidney Disease study, an ongoing prospective observational national cohort study CKD stage G3 A1-3 or G1-2 overt...
Abstract Introduction of the nanobody caplacizumab was shown to be effective in treatment acquired thrombotic thrombocytopenic purpura (aTTP) acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and use for a minimum 30 days after stopping daily PEX. This study retrospective, observational analysis 60 patients from 29 medical centers Germany. Immunosuppressive led rapid normalization ADAMTS13 activities (calculated median, 21 days). In 35 patients,...
IntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic disease. Results from the prospective clinical trial ravulizumab (NCT02949128) reveal rapid resolution TMA in patients with aHUS, sustained efficacy safety 26-week initial evaluation period.MethodsThe aim this analysis...
The protein kinase C (PKC)-β isoform has been implicated to play a pivotal role in the development of diabetic kidney disease. We tested this hypothesis by inducing nephropathy PKC-β–deficient (PKC-β−/−) mice. studied nondiabetic and streptozotocin-induced PKC-β−/− mice compared with appropriate 129/SV wild-type After 8 weeks diabetes, high-glucose–induced renal glomerular hypertrophy, as well increased expression extracellular matrix proteins such collagen fibronectin, was reduced...
Background Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss high molecular weight proteins in urine usually associated with decreased expression slit diaphragm proteins. Nephrin, major component glomerular and nephrin has been well described rodent models experimental diabetes as human Methodology/Principal Findings In this manuscript we analyzed role PKC-alpha (PKCα) on endocytosis podocytes. We found that treatment mice a PKCα-inhibitor (GÖ6976)...
BackgroundAcquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life‐threatening autoimmune microangiopathy. Current standard of care therapeutic plasma exchange, immunosuppression, and caplacizumab, an anti‐von Willebrand factor nanobody, which effective in treating aTTP episodes.Patients/MethodsHere we report on seven episodes treated without exchange six female patients Germany Austria. Two were initial presentations aTTP; five instances, experienced relapse. In four episodes,...
ABSTRACT Background Osteopontin (OPN), synthesized in the thick ascending limb of Henle's loop and distal tubule, is involved pathogenesis kidney fibrosis, a hallmark failure (KF). In cohort chronic disease (CKD) patients, we evaluated OPN's association with markers KF. Methods OPN was measured from baseline serum samples German Chronic Kidney Disease study participants. Cross-sectional regression models for estimated glomerular filtration rate (eGFR) urinary albumin-to-creatinine ratio...
In pregnancy-related atypical hemolytic uremic syndrome (p-aHUS), transferring recommendations for treatment decisions from nonpregnant cohorts with thrombotic microangiopathy (TMA) is difficult. Although potential causes of p-aHUS may be unrelated to inherent complement defects, peripartal complications such as postpartum hemorrhage (PPH) or (pre)eclampsia Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) unrecognized drivers activation.
<h2>Abstract</h2> The haemolytic uraemic syndromes (HUS) are a heterogeneous group of conditions only some which mediated by complement (CaHUS). We report the outcome 2023 International Society Nephrology HUS Forum where global panel experts considered current state art, identified areas uncertainty, and proposed optimal solutions. Areas uncertainty for future research included: nomenclature HUS; novel testing strategies; identification biomarkers; genetic predisposition to aHUS; dosing...
Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of negative charges the basement membrane, and changes slit-membrane diaphragm composition. We have recently shown that protein kinase C alpha (PKCalpha)-deficient mice are protected against development albuminuria under conditions. here tested hypothesis PKCalpha mediates hyperglycemia-induced downregulation slit-diaphragm nephrin. After 8 weeks streptozotocin (STZ)-induced hyperglycemia expression glomerular...