Last update 01 Nov 2024

Balkan Nephropathy

Last update 01 Nov 2024

Basic Info

Synonyms

BALKAN ENDEMIC NEPHROPATHY, BEN, Balkan Endemic Nephropathy

+ [28]

Introduction

A form of chronic interstitial nephritis that is endemic to limited areas of BULGARIA, the former YUGOSLAVIA, and ROMANIA. It is characterized by a progressive shrinking of the KIDNEYS that is often associated with uroepithelial tumors.

Drugs associated with Balkan Nephropathy

Traxivitug

Target

Capsid protein VP1

Mechanism

Capsid protein VP1 inhibitors

Active Org.-

Originator Org.

Novartis Pharma AG

Active Indication-

Inactive Indication

Balkan Nephropathy [+3]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Balkan Nephropathy

NCT04323904 / RecruitingNot ApplicableIIT

Hantavirus Registry Gathers Knowledge on Epidemiology, Clinical Course, Prognostic Factors and Molecular Characteristics for Hantavirus Infections and Their Complications (HantaReg)

Hantavirus disease are zoonotic infections and remain a clinical challenge with globally increasing incidence and multiple serious outbreak situations in Europe within the last years. Hantavirus disease encompasses two clinical syndromes, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. Depending on the causative Old World hantavirus species, clinical course of HFRS can vary from mild to moderate to severe.
At present, there is no specific therapy available for hantavirus disease. As the clinical course of hantavirus disease is dependent on the causing viral pathogen and as there worrisome hints that clinical course HFRS and HCPS overlap, further studies with regard to the disease course are mandatory. Furthermore, the examination of attributable mortality and costs of hantavirus disease will need to be studied on a multinational basis and therefore HantaReg will particularly use a matched case control design.

Start Date04 Mar 2020

Sponsor / Collaborator

University of Cologne Executive School GmbH

NCT02404155 / CompletedNot ApplicableIIT

Biomarker and Safety Study of Clozapine in Patients With Benign Ethnic Neutropenia (BEN)

Clozapine (CLZ) is the most effective antipsychotic for treatment-refractory schizophrenia (SZ). Despite the overwhelming evidence of superior efficacy, CLZ is infrequently prescribed in the US, at a considerably lower rate than the estimated prevalence of treatment-resistant SZ, especially for African-Americans (AA). Recent evidence suggests that low Absolute Neutrophil Counts (ANC), either at baseline or during treatment are a significant barrier to CLZ use in AA patients in the US, where guidelines mandate CLZ discontinuation if ANC drops below 1500 cells/mm3. The investigators group has found that discontinuation of CLZ in AA patients is over twice that in European-American (EA) patients (N
400; 42% vs.19%, P=0.041) and initiation rates are 50% lower. In a Statewide study (N=1875), the investigators reported that discontinuation was more frequently due to neutropenia in the AA sample, though no AA had developed agranulocytosis (8 cases in EA). Benign Ethnic Neutropenia (BEN) in people of African ancestry, including AAs, identifies a group (50% of AA) with low ANCs but no increased risk of agranulocytosis or infection. Low baseline or in-treatment fluctuations requiring CLZ discontinuation under current prescribing guidelines are common in CLZ-treated persons with BEN. In the investigators recent pilot study of N=12 AA patients with BEN, treatment was safely and successfully continued with CLZ despite low baseline ANC (outside current guidelines). Recent evidence implicates a polymorphism in the Duffy Antigen Receptor Chemokine (DARC) gene in the pathophysiology of BEN. In homozygotes (FY-/-) for the DARC null allele, mean within-subject neutrophil counts are reduced, resulting in sporadic ANC <1500 cells/mm3 in 10-15% of people with the allele. In population studies, the FY-/- genotype is found in 0.01% of EAs, 99.3% of sub-Saharan Africans (SSA), and 68% of AAs. Further, a missense DARC mutation has been reported to interact with the DARC FY-/- in determining low WBC in AAs. Normal patterns of week-to-week fluctuation in ANC levels in individuals of African ancestry with BEN and the DARC null genotype are not known, and no published research has examined variation in ANC in African ancestry CLZ-treated SZ patients with BEN and the DARC null genotype (FY-/-). Such data are also lacking on individuals with BEN without the DARC null genotype. Conducting such research will generate genetic marker and safety data that could be used to expand access to CLZ for AA patients who otherwise are eligible to receive this superior treatment option.

Start Date01 Jul 2015

Sponsor / Collaborator

University of Maryland Baltimore

NCT02455375 / CompletedNot Applicable

Puumala Hantavirus Infection in France: Evaluation of Commercial Assays for the Detection of Antibodies Against This Virus and the Use of Urine Samples for the Molecular Detection of This Infection

Routine Puumala virus (PUUV) infection diagnosis is performed using serological commercial kits of which performances have not been established in real life, which use recombinant protein from strains from Central or North Europe. Molecular diagnostic of these infection is not the rule. Consequently the objectives of the project are to evaluate the performances of the serological commercial assays in real life in France and to assess the use of urine versus plasma for the molecular diagnostic of this infection.

Start Date01 Jul 2015

Sponsor / Collaborator

Centre Hospitalier de Charleville-Mézières

[+1]

100 Clinical Results associated with Balkan Nephropathy

100 Translational Medicine associated with Balkan Nephropathy

0 Patents (Medical) associated with Balkan Nephropathy

1,143

Literatures (Medical) associated with Balkan Nephropathy

01 Oct 2024·Biotechnology and Applied Biochemistry

Cross‐reactivity of hantavirus antibodies after immunization with PUUV antigens

Article

Author: Rizvanov, Albert ; Khaiboullina, Svetlana ; Baranwal, Manoj ; Hamza, Shaimaa ; Khaertynova, Ilsiyar ; Sharma, Diksha ; Garanina, Ekaterina ; Shakirova, Venara ; Pavelkina, Vera ; Markelova, Maria ; Martynova, Ekaterina ; Shkair, Layaly

AbstractNephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross‐reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross‐reactive with serum from MVs immunized small mammals. These cross‐reactive epitopes were located in oligomerization perinuclear targeting and Daxx‐interacting domains. Most cross‐reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross‐reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

14 Aug 2024·Journal of Agricultural and Food Chemistry

Positive Feedback Mechanism in Aristolochic Acid I Exposure-Induced Anemia and DNA Adduct Formation: Implications for Balkan Endemic Nephropathy

Article

Author: Chan, Wan ; Ham, Yat-Hing ; Pavlović, Nikola M. ; Wang, Shuangshuang ; Chin, Man-Lung ; Pan, Guanrui

Balkan endemic nephropathy (BEN) is a chronic kidney disease that predominantly affects inhabitants of rural farming communities along the Danube River tributaries in the Balkans. Long-standing research has identified dietary exposure to aristolochic acids (AAs) as the principal toxicological cause. This study investigates the pathophysiological role of anemia in BEN, noting its earlier and more severe manifestation in BEN patients compared to those with other chronic kidney diseases. Utilizing a mouse model, our research demonstrates that prolonged exposure to aristolochic acid I (AA-I) (the most prevalent AA variant) leads to significant red blood cell depletion through DNA damage, such as DNA adduct formation in bone marrow, prior to observable kidney function decline. Furthermore, in vitro experiments with kidney cells exposed to lowered oxygen and pH conditions mimicking an anemia environment show enhanced DNA adduct formation, suggesting increased AA-I mutagenicity and carcinogenicity. These findings indicate for the first time a positive feedback mechanism of AA-induced anemia, DNA damage, and kidney impairment in BEN progression. These results not only advance our understanding of the underlying mechanisms of BEN but also highlight anemia as a potential target for early BEN diagnosis and therapy.

01 Aug 2024·NeuroImage

Age-dependent functional development pattern in neonatal brain: An fMRI-based brain entropy study

Article

Author: Zhao, Zhiyong ; Shuai, Yifan ; Wu, Dan ; Li, Mingyang ; Xu, Xinyi ; Wu, Yihan

The relationship between brain entropy (BEN) and early brain development has been established through animal studies. However, it remains unclear whether the BEN can be used to identify age-dependent functional changes in human neonatal brains and the genetic underpinning of the new neuroimaging marker remains to be elucidated. In this study, we analyzed resting-state fMRI data from the Developing Human Connectome Project, including 280 infants who were scanned at 37.5-43.5 weeks postmenstrual age. The BEN maps were calculated for each subject, and a voxel-wise analysis was conducted using a general linear model to examine the effects of age, sex, and preterm birth on BEN. Additionally, we evaluated the correlation between regional BEN and gene expression levels. Our results demonstrated that the BEN in the sensorimotor-auditory and association cortices, along the 'S-A' axis, was significantly positively correlated with postnatal age (PNA), and negatively correlated with gestational age (GA), respectively. Meanwhile, the BEN in the right rolandic operculum correlated significantly with both GA and PNA. Preterm-born infants exhibited increased BEN values in widespread cortical areas, particularly in the visual-motor cortex, when compared to term-born infants. Moreover, we identified five BEN-related genes (DNAJC12, FIG4, STX12, CETN2, and IRF2BP2), which were involved in protein folding, synaptic vesicle transportation and cell division. These findings suggest that the fMRI-based BEN can serve as an indicator of age-dependent brain functional development in human neonates, which may be influenced by specific genes.

News (Medical) associated with Balkan Nephropathy

23 Jan 2023

·www.nsmedicaldevices.com

Universal DX reports effective detection of CRC using combined technique

The study showed that early-stage (I-II) CRCs detection using the methylation and fragmentation features of cancer-related cfDNA regions in combination with a machine-learning algorithm showed 92% sensitivity at 94% specificity Universal DX will present the study results at ASCO Gastrointestinal Cancers Symposium. (Credit: Akram Huseyn on Unsplash) Universal Diagnostics (Universal DX) announced that the combination of cell-free DNA (cfDNA) methylation, fragmentation, and machine learning to detect early-stage colorectal cancer (CRC) was found to be effective as per an international, observational cohort study. The research from the US-based bioinformatics and multi-omics firm showed that early-stage (I-II) CRCs detection using the methylation and fragmentation features of cancer-related cfDNA regions in combination with a machine-learning algorithm showed 92% sensitivity at 94% specificity. The observational cohort study evaluated a patient sample set gathered from the US, Spain, Germany, and Ukraine. Its results will be presented at the ASCO Gastrointestinal Cancers Symposium. As per the results, the prediction model correctly classified 92% of CRC patients. The sensitivity per cancer stage varied from 91% for stage I, 92% for stage II, 91% for stage III, and 93% for stage IV. The multi-omics firm said that the specificity of the model was 94%, and it correctly identified 97% non-advanced adenoma (NAA), 93% benign colonoscopy findings of diverticulosis/diverticulitis, haemorrhoids, hyperplastic/inflammatory polyps (BEN), and 94% colonoscopy negative (cNEG). Universal DX COO Christian Hense said: “This study further validates and reinforces the work we are doing to develop tests that detect cancer in its earliest stages. “With a completely new sample set, we have again demonstrated highly-accurate early-stage CRC detection, further verifying the robustness of our technology and use of biomarkers to find traces of cancer in a person’s blood. “At Universal DX, we believe early detection is one of the most powerful tools for improving survival rates, and are encouraged to see these promising results once again.” Previously, the US-based firm demonstrated that non-invasive blood testing can be employed to detect CRC and pre-cancerous advanced adenomas (AA). The testing is done via the analysis of cell-free circulating tumour DNA (ctDNA) methylation, fragmentation, and microbiome patterns with single targeted sequencing analysis, combined with advanced computational biology and machine learning algorithms. Last year, the company expanded early-stage colorectal cancer detection to prognostics and stratification in order to improve outcomes and survival rates.

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Balkan Nephropathy

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