NETosis: an emerging therapeutic target in renal diseases.

Introduction: Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear and granular components. The primary role of NETS is to prevent the dissemination of microbes and facilitate their elimination. However, this process is accompanied by collateral proinflammatory adverse effects when the NET release becomes uncontrollable, or clearance is impaired. Although NET-induced organ damage is conducted primarily and indirectly via immune complexes and the subsequent release of cytokines, their direct effects on cells are also remarkable. NETosis plays a critical pathogenic role in several renal disorders, such as the early phase of acute tubular necrosis, anti-neutrophil cytoplasmic antibody-mediated renal vasculitis, lupus nephritis, thrombotic microangiopathies, anti-glomerular basement membrane disease, and diabetic nephropathy. Their substantial contribution in the course of these disorders makes them a desirable target in the therapeutic armamentarium. This article gives an in-depth review of the heterogeneous pathogenesis and physiological regulations of NETosis and its pivotal role in renal diseases. Based on the pathogenesis, the article also outlines the current therapeutic options and possible molecular targets in the treatment of NET-related renal disorders. Methods: We carried out thorough literature research published in PubMed and Google Scholar, including a comprehensive review and analysis of the classification, pathomechanisms, and a broad spectrum of NET-related kidney disorders. Conclusions: NETosis plays a pivotal role in certain renal diseases. It initiates and maintains inflammatory and autoimmune disorders, thus making it a desirable target for improving patient and renal outcomes. Better understanding and clinical translation of the pathogenesis are crucial aspects to treatment, for improving patient, and renal outcomes.

A unique case of anti-GBM disease with concomitant anti-PLA2R positivity.

BACKGROUND: Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods. CASE PRESENTATION: A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria. Symptoms developed one month after an upper respiratory tract infection. Laboratory results showed acute kidney injury, and hypoalbuminemia. Immunologic examination revealed both anti-GBM and anti-PLA2R positivity. Kidney biopsy demonstrated the histological features of Goodpasture's disease and anti-PLA2R positive membranous nephropathy. Steroid, cyclophosphamide, and plasmapheresis were commenced. Despite the combined immunosuppressive, the patient remained on renal replacement therapy. CONCLUSIONS: Microbial kidney injury can trigger multiple autoimmune diseases. The simultaneous occurrence of anti-glomerular basement (anti-GBM) disease and membranous nephropathy is extremely rare. Delayed recognition leads to delayed treatment, causing worse renal and patient outcomes, as well as increased financial costs.

Diagnostic and Therapeutic Approach in ANCA-Associated Glomerulonephritis: A Review on Management Strategies.

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a destructive small vessel vasculitis affecting multiple organs. Renal involvement often leads to end-stage renal disease and increases mortality. Prompt diagnosis and initiation of adequate immunosuppressive therapy are critical for the best patient and kidney outcomes. However, considerable heterogeneity in symptoms and severity across the patients frequently hinder the diagnosis and management. The objective of this review is to emphasize the heterogeneity of the ANCA-associated vasculitis, facilitate the recognition and give guidance to the therapeutical possibilities. We present epidemiologic and risk factors, pathogenesis, and provide comprehensive clinical features of the disease. This article also focuses on the currently available therapeutic options and emerging cellular and molecular targets for the management of systemic and especially renal disease. We conducted extensive literature research published on PubMed and Google Scholar. We systematically reviewed, analyzed, and assembled databases, covering a broad spectrum of aspects of the disease. We compared and summarized the recommendations of two recent guidelines on ANCA-associated vasculitis. The incidence of ANCA-associated vasculitis, hence glomerulonephritis shows a steady increase. Familiarity with the presenting symptoms and laboratory abnormalities are necessary for rapid diagnosis. Early initiation of treatment is the key aspect for favorable patient and renal outcomes. A better understanding of the pathogenesis constantly leads to more targeted and therefore more efficient and less toxic treatment.

Kidney biopsy-based epidemiologic analysis shows growing biopsy rate among the elderly.

Systematic registration and examination of biopsy-related data in Central and Eastern Europe are scarce, while the health condition of the population is worse compared to other more developed countries. We aim to create a database and analyze the distribution and temporal variation of the renal biopsy diagnoses in Hungary, including the effect of the recent coronavirus pandemic. The diagnoses were standardized according to the recommendation of the European Renal Association. Native biopsy samples processed between January 1, 2006, and December 31, 2020, were analyzed. During the 15 years, 2140 native kidney biopsies were performed. The number of samples increased from 24.5 to 57.9 per million person-years and the median age from 37 to 51 years (p < 0.0001). The predominance of glomerular diseases was stable. The most frequent glomerulopathy was IgA nephropathy (21.5%), followed by focal segmental glomerulosclerosis (17.7%), and membranous nephropathy (15.7%). Trends showed the rise of ANCA-associated vasculitis. During the coronavirus pandemic, there was a decrease in the number of kidney biopsies and the proportion of membranous nephropathies. The diagnostic trends in our database showed increasing biopsy rates among the elderly and the growing frequencies of age-related diseases, which emphasizes the importance of altering medical focus according to demographic changes in this area.

Prevalence of Cilioretinal Arteries: A systematic review and a prospective cross-sectional observational study.

PURPOSE: To review studies focusing on cilioretinal arteries (CLRA) in order to assess the overall prevalence and establish the prevalence of CLRA in a Hungarian Caucasian population. METHODS #1: Systematic literature review of published studies with at least 100 participants. METHODS #2: Non-mydriatic digital colour photographs were taken of 1000 consecutively enrolled healthy Caucasian young adult volunteers. Images were graded by two trained independent observers. Number and location of identified cilioretinal arteries were recorded and statistically analysed. RESULTS #1: Prevalence of CLRA ranges from 6.9% to 49.5%. Detection with fluorescein angiography yields the highest values followed by fundus photography and ophthalmoscopy. Unilateral presence of CLRA is between 70.30% and 93.65%, and temporal location is between 80.77% and 100%. RESULTS #2: We found at least one CLRA in 36.5% of the participants and in 22.75% of all the examined eyes. Cilioretinal arteries (CLRA) were unilateral in 75.34% and bilateral in 24.66%. Of all the identified CLRA, 96.16% were originating from the temporal rim of the optic disc. We identified at least one temporal CLRA supplying the macula in 28% of the participants and 16.95% of the examined eyes. CONCLUSION: Prevalence of CLRA varies depending on identification method. Unilateral presence is unequivocally more frequent similarly to temporal location. From a risk of bias standpoint, high-quality studies are rare. Our data on the distribution pattern of CLRA are similar to that in the international literature. Based on our findings, we assume that slightly more than one-third of the Hungarian Caucasian population has a CLRA.

The dark side of the Sun: multimodal imaging of a solar retinopathy case / [A Nap sötét oldala: retinopathia solaris esetének multimodális bemutatása]

Solar retinopathy is the photochemical and thermic injury of the retinal photoreceptors and the pigment epithelium caused by ultraviolet (UV) radiation. As a consequence, the most common symptoms are visual acuity deterioration, blurred vision and positive scotoma. Optical coherence tomography (OCT), microperimetry and fluorescein angiography (FLA) are helpful in determining the diagnosis. Authors present an 18-year-old male having central scotomas affecting both eyes who presented at the Department of Ophtalmology of Semmelweis University. OCT scans revealed a localised defect and hyperreflectivity of certain retinal layers and microperimetry examination detected decreased retinal sensitivity consistent with the lesions. After a follow-up of 6 months, the defect of the right eye became more subtle and the one on the left disappeared completely. Microperimetry results correlated with OCT findings. Subjective symptoms on the right eye decreased significantly and they do not affect his daily life anymore, symptoms on the left eye discontinued. Currently, no specific therapy exists for solar retinopathy. Symptoms and defects in favourable cases normalise in 3­6 months which highlights the importance of public health education and prevention. Orv Hetil. 2020; 161(16): 632­636.

Witch Hazel Significantly Improves the Efficacy of Commercially Available Teat Dips.

Bovine intramammary infections (IMIs) are the main cause of economic loss in milk production. Antibiotics are often ineffective in treating infections due to antimicrobial resistance and the formation of bacterial biofilms that enhance bacterial survival and persistence. Teat dips containing germicides are recommended to prevent new IMIs and improve udder health and milk quality. IMIs are often caused by staphylococci, which are Gram-positive bacteria that become pathogenic by forming biofilms and producing toxins. As a model for a teat dip (DIP), the BacStop iodine-based teat dip (DIP) was used. Witch hazel extract (whISOBAX (WH)) was tested because it contains a high concentration of the anti-biofilm/anti-toxin phenolic compound hamamelitannin. We found that the minimal inhibitory or bactericidal concentrations of DIP against planktonic S. epidermidis cells increased up to 160fold in the presence of WH, and that DIP was 10-fold less effective against biofilm cells. While both DIP and WH are effective in inhibiting the growth of S. aureus, only WH inhibits toxin production (tested for enterotoxin-A). Importantly, WH also significantly enhances the antibacterial effect of DIP against Gram-negative bacteria that can cause IMIs, like Escherichia coli and Pseudomonas aeruginosa. Put together, these results suggest that the antibacterial activity of DIP combined with WH is significantly higher, and thus have potential in eradicating bacterial infections, both in acute (planktonic-associated) and in chronic (biofilm-associated) conditions.

In-Vitro Inhibition of Staphylococcal Pathogenesis by Witch-Hazel and Green Tea Extracts.

whISOBAX (WH), an extract of the witch-hazel plant that is native to the Northeast coast of the United States, contains significant amounts of a phenolic compound, Hamamelitannin (HAMA). Green tea (GT) is a widely consumed plant that contains various catechins. Both plants have been associated with antimicrobial effects. In this study we test the effects of these two plant extracts on the pathogenesis of staphylococci, and evaluate their effects on bacterial growth, biofilm formation, and toxin production. Our observations show that both extracts have antimicrobial effects against both strains of S. aureus and S. epidermidis tested, and that this inhibitory effect is synergistic. Also, we confirmed that this inhibitory effect does not depend on HAMA, but rather on other phenolic compounds present in WH and GT. In terms of biofilm inhibition, only WH exhibited an effect and the observed anti-biofilm effect was HAMA-depended. Finally, among the tested extracts, only WH exhibited an effect against Staphylococcal Enterotoxin A (SEA) production and this effect correlated to the HAMA present in WH. Our results suggest that GT and WH in combination can enhance the antimicrobial effects against staphylococci. However, only WH can control biofilm development and SEA production, due to the presence of HAMA. This study provides the initial rationale for the development of natural antimicrobials, to protect from staphylococcal colonization, infection, or contamination.