Nadja Grobe

Nadja Grobe
Renal Research Institute

PhD

About

79
Publications
8,614
Reads
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1,020
Citations
Citations since 2016
42 Research Items
801 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Introduction
Ten years of experience in research and teaching of analytical chemistry, biochemistry and biomedical sciences. Qualitative and quantitative sample analysis using chromatography and mass spectrometry. Expertise in proteomics, metabolomics, enzymology and in vitro / in vivo pharmacological / toxicological studies. Experience in government, academia and non-profit. Ph.D. in Biochemistry. U.S. citizen.
Additional affiliations
November 2017 - present
Renal Research Institute
Position
  • Researcher
March 2015 - March 2018
Wright State University Boonshoft School of Medicine
Position
  • Professor (Associate)
March 2015 - September 2017
Wright-Patterson Air Force Base
Position
  • Analytical Chemist

Publications

Publications (79)
Article
Oxidative stress (OS) is essential in uremia‐associated comorbidities, including renal anemia. Complications experienced by hemodialysis (HD) patients, such as hypoxemia and uremic toxins accumulation, induce OS and premature death of red blood cells (RBC). We aimed to characterize reactive oxygen species (ROS) production and antioxidant pathways i...
Article
The aim of the paper is to summarize the current understanding of the molecular biology of arteriovenous fistula (AVF). It intends to encourage vascular access teams, care providers, and scientists, to explore new molecular tools for assessing the suitability of patients for AVF as vascular access for maintenance hemodialysis (HD). This review also...
Article
Full-text available
Background In hemodialysis patients, a third vaccination is frequently administered to augment protection against coronavirus disease 2019 (COVID-19). However, the newly emerged B.1.1.159 (Omicron) variant may evade vaccinal protection more easily than previous strains. It is of clinical interest to better understand the neutralizing activity again...
Article
Full-text available
Erythropoietin deficiency is an extensively researched cause of renal anemia. Etiology and consequences of shortened red blood cell (RBC) life span in chronic kidney disease (CKD) are less well understood. Traversing capillaries requires RBC geometry changes, a process enabled by adaptions of the cytoskeleton. These changes are mediated by transien...
Article
BACKGROUND AND AIMS SARS-CoV-2 antibody titers after two doses of vaccination decrease over time. Hemodialysis patients are especially vulnerable to COVID-19 as they are immunocompromised, putting them at higher risk of infection and poorer response to vaccines. Therefore, administrating the third dose (‘booster’) in these patients is key to reduce...
Article
Introduction: Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonl...
Article
Full-text available
Background/aims: Chronic kidney disease is frequently accompanied by anemia, hypoxemia, and hypoxia. It has become clear that the impaired erythropoietin production and altered iron homeostasis are not the sole causes of renal anemia. Eryptosis is a process of red blood cells (RBC) death, like apoptosis of nucleated cells, characterized by Ca2+ in...
Article
Background and Aims Dialysis patients are at higher risk for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Longevity of antibody response to SARS-CoV-2 infection remains unclear. It is reported that maintenance hemodialysis (MHD) patients can mount an antibody response that is similar in intensity and timing to the non-dialy...
Article
Background and Aims Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits cellular and humoral immune responses. In patients with coronavirus disease 2019 (COVID-19), IgM, IgA, and IgG antibodies against SARS-CoV-2 emerge within a few days and can be detected in several body fluids, such as serum and oral fluids. End S...
Article
Full-text available
Background Pool testing strategies combine samples from multiple people and test them as a group. A pool testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settin...
Article
Full-text available
Activation of the renin angiotensin system plays a pivotal role in the regulation of blood pressure, which is mainly attributed to the formation of angiotensin-II (Ang II). The actions of Ang II are mediated through binding to the Ang-II type 1 receptor (AT1R) which leads to increased blood pressure, fluid retention, and aldosterone secretion. In a...
Article
Full-text available
Background: To date it is unclear whether SARS-CoV-2 is present in spent dialysate from peritoneal dialysis (PD) patients with COVID-19. Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from chronic PD patients with confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from COVID-19 positive PD patients...
Article
Full-text available
Red blood cells (RBC) are the most abundant cells in the blood. Despite powerful defense systems against chemical and mechanical stressors, their life span is limited to about 120 days in healthy humans and further shortened in patients with kidney failure. Changes in the cell membrane potential and cation permeability trigger a cascade of events t...
Conference Paper
Full-text available
Background: Tryptophan (Trp) loss in kidney failure patients is likely to be associated with poor nutritional status and depletion due to dialysis. However, Trp removal with medium cutoff (MCO) membranes has not been investigated. Here, we compared Trp reduction ratios (RR) between an MCO dialyzer and a high-flux polysulfone (HFPS) dialyzer Methods...
Conference Paper
Full-text available
Background: To our knowledge no study has ever evaluated the use of middle cut-off membranes (MCO) with online hemodiafiltration (OL-HDF). This study aims to show if the combination of OL-HDF with MCO can achieve a higher reduction ratio of some uremic toxins in comparison to regular OL-HDF. Methods: Patients from our hemodialysis unit were treated...
Conference Paper
Full-text available
Background: We have previously described that indoxyl sulfate promotes red blood cells (RBC) ROS generation through organic anion transporter 2 as well as NADPH oxidase activity-dependent and GSH-independent mechanisms (Dias et al., 2018). However, there is little information regarding pathways of antioxidant balance to protect RBC from extensive o...
Article
Full-text available
Background and Aims We have previously described that indoxyl sulfate promotes red blood cells (RBC) ROS generation through organic anion transporter 2 as well as NADPH oxidase activity-dependent and GSH-independent mechanisms (Dias et al., 2018). However, there is little information regarding pathways of antioxidant balance to protect RBC from ext...
Article
Background and Aims Pervasive sensing technologies allow healthcare providers to gain additional insights into patient’s status outside the clinical setting. In order to adopt widespread use of remote monitoring devices we must first study the feasibility of their use. We aim to quantify how long patients will use a wearable device before requiring...
Article
Full-text available
Background and Aims Intradialytic hypoxemia is associated with oxidative stress, endothelial dysfunction, inflammation, higher erythropoietin requirements, and higher all-cause hospitalization and mortality in hemodialysis (HD) patients (Meyring-Wosten, et al., 2016). The aim of the present study was to further expand our insights into the hypoxia-...
Article
Background and Aims It is projected that in 2030, 14.5 million people will have end stage kidney disease and need kidney replacement therapy, yet only 5.4 million will receive it due to economic, social, and political factors. We have proposed allo-hemodialysis (alloHD) as a simple and low-cost HD alternative (https://www.kidneynews.org/kidney-news...
Article
Rationale: Kidney homeostasis is critically determined by the coordinated activity of the renin-angiotensin system (RAS) including the balanced synthesis of its main effector peptides angiotensin (Ang) II and Ang-(1-7). The condition of enzymatic overproduction of Ang II relative to Ang- (1-7) is termed RAS dysregulation, and leads to cellular sign...
Article
Full-text available
Background/aims: Red blood cell (RBC) death could contribute to anemia in chronic kidney disease (CKD) patients. Recent observational research has suggested a relationship between RBC death (eryptosis) and hypoxemia in hemodialysis patients. Thus, we studied the isolated and joint effects of a uremic toxin (indoxyl sulfate; IS) and hypoxia on RBC...
Article
Renin angiotensin system (RAS) plays a key role in the pathogenesis and progression of hypertension and renal injury. Angiotensin-II (Ang-II) type 1 receptor (AT1R) mediates the actions of Ang II to increase blood pressure, fluid retention, and aldosterone secretion. Ang II is involved in cell injury, vascular remodeling, and inflammation by releas...
Article
Previously, we demonstrated that treatment of rats with myo-inositol plus ethanolamine (ME) elevated brain ethanolamine plasmalogens (PE-Pls) and protected against phosphine-induced oxidative stress. Here we tested the hypothesis that ME treatment elevates PE-Pls in neuro-2A (N2A) cell culture system and protects against hydrogen peroxide (H2O2)-in...
Article
Environments combining JP-8 jet fuel exposure with heightened ambient noise may accelerate hearing loss induced by noise. To reduce animal use and facilitate kinetic modeling of this military aviation fuel, tissue-specific parameters are required, including water, protein and lipid content. However, tissues involved in hearing, including cochlea, b...
Article
Full-text available
Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecul...
Preprint
Full-text available
Acute exposure to high concentrations of H 2 S causes severe brain injury and long-term neurological disorders. The mechanisms of H 2 S-induced neurodegeneration are not known. To better understand the cellular and molecular mechanisms of H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to search for key molecules...
Chapter
The renin angiotensin system (RAS) is a highly complex enzymatic system consisting of multiple peptide hormones, enzymes, and receptors. A thorough characterization of angiotensin peptide metabolism is crucial for understanding pathological states associated with an imbalanced RAS. Here, we describe two matrix-assisted laser desorption/ionization (...
Article
Full-text available
Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as more humane methods of euthanasia. In this study, we examined 3 commonly used euthanasia methods in mice: intrap...
Article
Full-text available
Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative v...
Article
The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and act...
Article
Rodent euthanasia with CO2 by using gradual displacement of 10% to 30% of the chamber volume per minute is considered acceptable by the AVMA Panel on Euthanasia. However, whether a 50% to 100% chamber replacement rate (CRR) of CO2 is more painful or distressful than 10% to 30% CRR is unclear. Therefore, we examined physiological and behavioral para...
Article
Genotyping of genetically-engineered mice is necessary for the effective design of breeding strategies and identification of mutant mice. This process relies on the identification of DNA markers introduced into genomic sequences of mice, a task usually performed using the polymerase chain reaction (PCR). Clearly, the limiting step in genotyping is...
Conference Paper
Cardiovascular and renal pathology is frequently associated with a hyperactivated Renin-Angiotensin-System (RAS) and increased levels of its vasoconstrictive metabolite Angiotensin II. RAS blockade is a widely used therapeutic approach to treat hypertension and prevent hypertonic nephropathy. Due to a well-documented vasodilatory and renoprotective...
Article
The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal system. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to: 1) demonstrate the presence of an endogenous and functional RAS in COS7, and...
Article
It is well documented that angiotensin (Ang) II contributes to kidney disease progression. The protease prolyl carboxypeptidase (PRCP) is highly expressed in the kidney and may be renoprotective by degrading Ang II to Ang-(1-7). The aim of the study was to investigate whether renal PRCP protein expression and activity are altered in two-kidney, one...
Article
Full-text available
Key Points The reduced thrombosis in Klkb1−/− mice is not by defective contact activation. Overexpressed renal Mas with elevated plasma prostacyclin increases aortic Sirt1 and KLF4 and reduces aortic TF protecting Klkb1−/− mice.
Article
Diabetes and its associated chronic kidney disease (CKD) is a major health burden and there is an urgent need for new sensitive biomarkers to detect and monitor the progression of CKD. Albuminuria is still the gold standard for the evaluation of kidney function. However, its sensitivity and reliability have recently been questioned. ACE2 is highly...
Article
The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal system. COS-7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aim of this study was to 1) demonstrate the presence of an endogenous and functional RAS in COS7 cells a...
Article
Full-text available
Aminopeptidase-A (APA) is a less well-studied enzyme of the renin angiotensin system. We propose that it is involved in cardiac Angiotensin (Ang) metabolism and its pathologies. Ang-(1-7) can ameliorate remodeling after myocardial injury. The aims of this study are to (1)Develop mass spectrometric (MS) approaches for the assessment of Ang processin...
Article
Full-text available
Angiotensin converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (Ang-II) to Ang-(1-7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM...
Article
Prekallikrein (PK) is the precursor for plasma kallikrein (KK), a serine protease that participates in contact activation. KK promotes inflammation by cleaving high-molecular-weight kininogen (HK) to liberate bradykinin (BK), which binds to the bradykinin B2 receptor (B2R) in the intravascular compartment to induce vasodilation and increase vascula...
Article
There are 26 million adults with chronic kidney disease (CKD) in the U.S. and the incidence continues to increase. It is well documented that the activation of the renin angiotensin system and the elevated formation of angiotensin (Ang) II both contribute to renal pathophysiology in CKD. Emerging evidence suggests that the Ang II degrading protease...
Article
Angiotensin Type 1 (AT1) receptors are involved in cardiovascular pathology. Lozartan, the AT1 receptor blocker, in combination with exercise has been shown to be effective in improving cardiac performance. The goal of the study was to investigate the role of AT1a receptors on cardiac function, and exercise tolerance in response to aerobic exercise...
Article
Aminopeptidase A (APA) is a metalloprotease that is activated in cardiovascular diseases. Ang-(1-7) has been shown to have beneficial effects in myocardial injury. The aims of this study are to (1) Test the role of APA in cardiac pathology using the myocardial infarction (MI) model, (2) Investigate the role of APA in Ang-(1-7) metabolism (3) Explor...
Article
Full-text available
Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in t...
Article
Angiotensin converting enzyme 2 (ACE2) catalyzes the conversion of angiotensin (Ang) II into Ang-(1-7). The present study examined the contribution of alternative renal peptidases to ACE2 independent formation of Ang-(1-7) using newly established proteomic approaches and genetic mouse models. In situ and in vitro mass spectrometric characterization...
Article
Full-text available
Bradykinin B2 receptor-deleted mice (Bdkrb2(-/-)) have delayed carotid artery thrombosis times and prolonged tail bleeding time resulting from elevated angiotensin II (AngII) and angiotensin receptor 2 (AT2R) producing increased plasma nitric oxide (NO) and prostacyclin. Bdkrb2(-/-) also have elevated plasma angiotensin-(1-7) and messenger RNA and...
Article
Mass spectrometric (MS) methods were used to study angiotensin (Ang) metabolism in mouse heart. The focus was on Ang II, Ang-(1-7) and Ang III. Goals were: 1) develop and optimize new technique for in situ assessment of Ang II processing within the myocardium using matrix-assisted laser desorption ionization (MALDI) imaging and 2) to validate resul...
Article
Diabetic nephropathy is one of the major microvascular complications of diabetes which eventually manifests into end stage renal disease. Alteration in renin-angiotensin system (RAS) is considered to be the primary cause underlying this implication. Emerging evidence suggests that the biological actions of Ang II may be opposed by the formation of...
Article
The kidney plays a pivotal role in acid-base balance. Hydrogen and bicarbonate titration through the nephron produces ranges in urinary pH from 4.5 to 8. All of the components of the renin angiotensin system (RAS) are expressed in the kidney and intrarenal angiotensin II (Ang II) and Ang-(1-7) are formed by multiple independent enzymatic pathways....
Article
Emerging evidence suggests that activation of the proteases, Ang converting enzyme 2 (ACE2) and prolyl carboxypeptidase (PCP), are associated with metabolic pathologies. We hypothesized that global loss of ACE2 affects high fat diet induced renal expression of PCP. ACE2 knockout (ACE2KO) and wild type (WT) male mice were fed a 60% high fat (HF) or...
Article
The assumption that CYP2D1 is the corresponding rat cytochrome to human CYP2D6 has been revisited using recombinant proteins in direct enzyme assays. CYP2D1 and 2D2 were incubated with known CYP2D6 substrates, the three morphine precursors thebaine, codeine and (R)-reticuline. Mass spectrometric analysis showed that rat CYP2D2, not 2D1, catalyzed t...