Podcasts about Glomerulonephritis

Drs. Luan D. Truong, Richard J. Johnson, and Gabriela Espinosa Garcia discuss the findings from their study, "Production of Acetylcholine by Podocytes and its Protection from Kidney Injury in Glomerulonephritis," with JASN Deputy Editor Alessia Fornoni.

Listen as Dr. London Smith (.com) and his producer Cameron discuss Postinfectious Glomerulonephritis with special guest Andrew Nice Clay (Jason Luna). Not so boring! https://www.patreon.com/join/jockdocpodcast Hosts: London Smith, Cameron Clark. Guest: Jason Luna. Produced by: Dylan Walker Created by: London Smith

Listen as Dr. London Smith (.com) and his producer Cameron discuss Membranous Glomerulonephritis on the podcast's 5th year anniversary with a big new budget. Not so boring! https://www.patreon.com/join/jockdocpodcast Hosts: London Smith, Cameron Clark. Produced by: Dylan Walker Created by: London Smith

Wie sich U-Stix-Befunde richtig deuten lassen und rasch zur korrekten Diagnose führen – Fallbeispiele inklusive.

Listen as Dr. London Smith (.com) and his producer Cameron discuss Focal Segmental Glomerulonephritis with special guest Doctor Hugh Morris (Bryan Spellman). Not so boring! https://www.patreon.com/join/jockdocpodcast Hosts: London Smith, Cameron Clark. Guest: Bryan Spellman. Produced by: Dylan Walker Created by: London Smith

Join our team in a discussion about diagnosis and treatment of glomerulonephritis, a common cause of kidney failure. We explore new treatment options and ways to engage patients in conversations about these options. Additionally, we unpack how to diagnose and monitor glomerulonephritis. This discussion also includes challenges faced both by patients and providers with regard to glomerulonephritis, especially for women of child-bearing age.

This episode covers glomerulonephritis.Written notes can be found at https://zerotofinals.com/medicine/renal/glomerulonephritis/ or in the renal medicine section of the 2nd edition of the Zero to Finals medicine book.The audio in the episode was expertly edited by Harry Watchman.

We're taking a short break, but we'll be back in two week with a brand-new episode. Can't wait? Join our Kashlak family at patreon.com/curbsiders for access to twice-monthly bonus episodes… there are already 17 of them available to feed your brain hole! Yummy! Time Stamps* Kashlak's esteemed Chief of Nephrology, Dr Joel Topf @kidney_boy walks us through the evaluation and differentiation of nephrotic syndrome and glomerulonephritis. Embrace the kidney again as we sort the different diagnostics, managements, and prognosis for these two pathologies.  Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! | Transcript Time Stamps* *Note: Time Stamps refer to ad free version Intro, disclaimer, guest bio - 00:00 Picks of the Week - 3:10 Case from Kashlak - 6:30 Nephrotic syndrome definition- 12:30 Proteinuria evaluation - 15:04 Additional lab testing - 27:08; 40:09 Types of Nephrotic syndrome - 30:15 Mechanism of nephrotic syndrome edema - 33:08 Management of nephrotic syndrome - 44:07 Second Kashlak Case- Glomerulonephritis - 55:05 Treatment of glomerulonephritis - 65:05 Outro and post-credits scene - 73:20 Credits Producer, writer, infographic, cover art: Elena Gibson MD Hosts: Elena Gibson MD, Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP   Editor: Emi Okamoto MD (written); Clair Morgan of nodderly.com (audio) Guest: Joel Topf MD Sponsor - Pattern Life  Request your quotes online at patternlife.com/curbsiders

This podcast covers two papers, one describes a clinical workflow for incorporating whole exome sequencing and the other provides evidence genomic disorders contribute to monogenic CKD in adults and children.

The spaced learning series team tackles the case of a patient with a non-resolving pulmonary inflammatory syndrome, found to have a cavitary lesion on lung imaging with glomerulonephritis. Download CPSolvers App here RLRCPSOLVERS

Drs. Fernando Fervenza, Marta Casal Moura, and Ulrich Specks discuss the results of their study, "Maintenance of Remission and Risk of Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Renal Involvement."

Join Yvonne Brandenburg, RVT, VTS SAIM and Jordan Porter RVT, LVT, VTS SAIM as we talk about: When the kidney becomes damaged, but not JUST the kidneys, specifically the glomeruli.    Question of the Week What resources do you utilize for glomerulonephritis?  Leave a comment at https://imfpp.org/episode147  Resources We Mentioned in the Show  https://www.dvm360.com/view/glomerulonephritis-remains-important-cause-renal-disease-dogs https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/glomerular-disease-in-small-animals https://veterinarypartner.vin.com/default.aspx?pid=19239&id=4951842 https://vcahospitals.com/know-your-pet/glomerulonephritis-in-dogs   Thanks so much for tuning in. Join us again next week for another episode!  Want to earn some RACE approved CE credits for listening to the podcast? You can earn between 0.5-1.0  hour of RACE approved CE credit for each podcast episode you listen to.    Join the Internal Medicine For Vet Techs Membership to earn and keep track of your continuing education hours as you get your learn on!   Join now! http://internalmedicineforvettechsmembership.com/   Get Access to the Membership Site for your RACE approved CE certificates Sign up at https://internalmedicineforvettechsmembership.com  Get Access to the Technician Treasure Trove  Sign up at https://imfpp.org/treasuretrove    Thanks for listening!  – Yvonne and Jordan

Dan, Jack, and Sharmin discuss a case of dyspnea, and hypertension presented by Ann Marie. Dyspnea Secondary hypertension AKI overview Glomerulonephritis   Download CPSolvers App here Patreon website

Smitha and Simone tackle inpatient infections and glomerulonephritis as they work through a case presented by Anna. Schema: Infection in the inpatient Glomerulonephritis Download CPSolvers App here Patreon website

Today's Episode Today Dr. Suzanne Boyle reviews the case of a 22 year old male who presents with 3 days of "cola colored" urine. About Dr. Raj Dr Raj is a quadruple board certified physician and associate professor at the University of Southern California. He was a co-host on the TNT series Chasing the Cure with Ann Curry, a regular on the TV Show The Doctors for the past 7 seasons and has a weekly medical segment on ABC news Los Angeles. More from Dr. Raj www.BeyondThePearls.net The Dr. Raj Podcast Dr. Raj on Twitter Dr. Raj on Instagram Want more board review content? Crush Step 1 Step 2 Secrets Physiology by Physeo Step 1 Success Stories The InsideTheBoards Study Smarter Podcast The InsideTheBoards Podcast Study on the go for free! Download the Audio QBank by InsideTheBoards for free on iOS or Android. If you want to upgrade, you can save money on a premium subscription by customizing your plan until your test date on our website! Produced by Ars Longa Media To learn more about us and this podcast, visit arslonga.media. You can leave feedback or suggestions at arslonga.media/contact or by emailing info@arslonga.media. Produced by: Christopher Breitigan Executive Producer: Patrick C. Beeman, MD Legal Stuff InsideTheBoards is not affiliated with the NBME, USMLE, COMLEX, or any professional licensing body. InsideTheBoards and its partners fully adhere to the policies on irregular conduct outlined by the aforementioned credentialing bodies. The information presented in this podcast is intended for educational purposes only and should not be construed as professional or medical advice. Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode, Anna & Smitha review the schemas of Inflammation and Glomerulonephritis as they work through a case presented by Emma. Glomerulonephritis Inflammation – Overview   Download CPSolvers App here Patreon website

Paano natin binago ang Kautusan

Paano natin binago ang Kautusan

This episode talks about Glomerulonephritis and its causes.One of which is Post Streptococcal GN, which is also discussed in this episode.

Have a listen to this overview of glomerulonephritis, where we explain the various causes of nephrotic and nephritic syndrome!!!! ☺️☺️

Dr. Scott Cohen discusses how patients can manage glomerulonephritis, a group of kidney diseases.

A few articles in each issue are chosen by the EIC for their interest. The issue highlights include: laminin-521 –a novel GBM autoantigen, iron biomarkers & mortality in nondialysis kidney disease, & disparities among hemodialysis patients with COVID-19.

Dr. Augusto Vaglio provides a summary of his study, "Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood," on behalf of his colleagues.

Wai Lang Lau, MD discusses the histology and pathological scoring of IgA glomerulonephritis. She helps us to understand the genetics and pathophysiology as well as the heterogeneity of phenotype and she explains the latest treatment options – present and future.

As we wrap up our Alport Awareness Series, I am so excited to welcome to the show, Grant Bonebrake & Maddie Martin, Volunteer Patient Advocate Alport Foundation.  About Grant: Grant Bonebrake is a high school senior in San Diego, CA. He was misdiagnosed with the wrong kidney disease until age 11 when he experienced hearing loss that led to proper diagnoses of Alport syndrome, a rare genetic kidney disease. His involvement with Alport Syndrome Foundation led him to become an active patient advocate. In December 2020, Grant received the national RareVoice Award (Teen Category) for Legislative Advocacy from the EveryLife Foundation for Rare Diseases. He also volunteers with the Young Adult Representatives of Rare Disease Legislative Advocates program, and National Kidney Foundation. Grant is currently working with other teens to document the experiences and insights of young people living with Alport syndrome. About Maddie: Maddison Martin just turned 22. She was originally misdiagnosed with Glomerulonephritis at age 2 before receiving a formal diagnosis of Alport syndrome, via kidney biopsy, at 4-years-old. At the age of 20, she received the Gift of Life in the form of a kidney transplant from her high school attendance secretary, Tammy. Inspired by her Alport journey, Maddison is currently a nursing student and enjoys spending free time with her family. Listen in as Maddie & Grant share their personal journeys, the physical & emotional aspects of being a teen with rare disease and how they have embraced their diagnosis.  #AlportAwareness   

In todays episode, I discuss the pathophysiology, signs and symptoms, treatment and nursing interventions for post streptococcal glomerulonephritis. Let's Review!

IN THIS EPISODE: Is addiction an invisible disability? Ex-actress, sober wife, senior dog-mom and writer Henriette Ivanans answers that question while recounting her journey to sobriety following two kidney transplants. Ivanans, the author of “In Pillness and In Health,” was diagnosed with Glomerulonephritis (chronic inflammation of the kidneys) as a teenager while dealing with the death of her alcoholic father. Living in Winnipeg, MB, Ivanans goes into detail about what it's really like to be in a rehab facility, how she came to terms with her dad's addiction and whether film and television's portrayal of people struggling with such issues is really all that accurate. We invite you to leave your thoughts by visiting us on YouTube, Instagram at @whatsthedifferencepodcast, Facebook at @whatsthedifferencepodcast, or by email at whatsthedifferencepodcast@gmail.com, and through our website whatsthedifferencepodcast.ca. Thanks for tuning in! RECORDED: December 12, 2020 FIRST AIRED: April 22, 2021 AUDIO PRODUCTION: George Quarcoo

Renal Disorders: Acute Kidney injury, Chronic Kidney injury, Polycystic Kidney Disease, Pyelonephritis, Glomerulonephritis and many more.

Kashlak’s esteemed Chief of Nephrology, Dr Joel Topf @kidney_boy walks us through the evaluation and differentiation of nephrotic syndrome and glomerulonephritis. Embrace the kidney again as we sort the different diagnostics, managements, and prognosis for these two pathologies. Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! Credits Producer, writer, infographic, cover art: Elena Gibson MD Hosts: Elena Gibson MD, Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP Editor: Emi Okamoto MD (written); Clair Morgan of nodderly.com (audio) Guest: Joel Topf MD Sponsor: The American College of Physicians Join us for ACP Internal Medicine Meeting 2021: Virtual Experience for 3 days of interactive, livestreaming education and events April 29 through May 1—plus on-demand post-meeting access to CME credit for up to 3 years. “Early Bird” members get an additional $80 registration discount on top of their member discount. Visit annualmeeting.acponline.org and use the code IM21CURB. Register now—Early Bird savings end January 31st! Sponsor: VCU Health CE The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.

Sharmin, Rabih, Reza, and Arsalan tackle a schema for glomerulonephritis  Patreon website Download CPSolvers App here Schema Want to test your learning? Take our Episode Quiz

The completion of the Endocarditis for the Rheumatologist trilogy! This episode focuses on the glomerulonephritis of endocarditis as well as the immunologic abnormalities you can see on labs. Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. Intro :11 In this episode :22 Recap of previous episodes :39 About episode three 1:00 How labs can give a clue to endocarditis being a culprit 1:23 The immune complex nature of infective endocarditis 6:30 How do you measure immune complex? 9:10 What are the effects of immune complex formation on the organ systems? 12:37 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Cryoglobulins and rheumatoid factor in infective endocarditis 15:12 The kidneys and infective endocarditis 16:45 Glomerulonephritis and infective endocarditis 24:15 ANCA-positive vasculitis and infective endocarditis 29:09 A summary of infective endocarditis 32:21 Takeaways 33:28 A preview of next episode 33:48 Conclusion 34:12 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bayer AS, et al. N Engl J Med. 1976;295:1500-1505. Boils CL, et al. Kidney Int. 2015;87:1241-1249. Forte WC, et al. Arq Bras Cardiol. 2001;76:43-52. Hurwitz D, et al. Clin Exp Immunol. 1975;19:131-141. Langlois V, et al. Medicine (Baltimore). 2016;95:e2564. Levy RL, Hong R. Am J Med. 1973;54:645-652. Ma T-T, et al. PLoS One. 2014;9: https://doi.org/10.1371/journal.pone.0097843. Messias-Reason IL, et al. Clin Exp Immunol. 2002;127:310-315. Petersdorf RG. N Engl J Med. 1976;295:1534-1535. Spain DM, King DW. Ann Intern Med. 1952;36:1086-1089. Williams Jr RC, Kunkel HG. J Clin Invest. 1962;41:666-675. Tire squealing sound effect by Mike Koenig.

Dr. Joop Aendekerk, on behalf of his co-authors, reports on findings from the study "Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis."

Dr. Joop Aendekerk, on behalf of his co-authors, reports on findings from the study "Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis."

This episode covers glomerulonephritis!

This episode covers low complement glomerulonephritis!

This episode covers normal complement glomerulonephritis!

This episode covers the differential diagnosis for glomerulonephritis!

Niti Madan, MD, is currently a Professor of nephrology at UC Davis Medical Health Center. Dr Madan attended medical school at Punjab University, India, and then pursued residency at Southern Illinois University School of Medicine. She then obtained a fellowship in nephrology at the University of Texas at Houston. Dr Madan's research interests include: Glomerulonephritis, Hypertension, Critical Care Nephrology and Mindfulness in Nephrology. Do you really know how to make a commitment? Today, Dr. Niti Madan tells us exactly what that entails. She explains that we must learn how to honor our commitments. Whatever path we choose in life, we must commit to doing that the best we can. Truly honoring our commitments means devoting our practice to showing our best in whatever we do. Prove to yourself and others that you are willing to grow, evolve, and reach excellence. When you run into roadblocks, look for the guidance of your mentors: A strong mentor can help identify your potential, and push you toward your highest goals. Pearls of Wisdom: 1. Be persistent. Pursue your goals, whether this means becoming an academician or mentor. 2. Choose the right mentors. Know the types of people you want to emulate. 3. Stay committed. Be honest with yourself, your commitments, your mentors, your patients, and especially yourself. 4. Stay positive. Be mindful of the things that you do and the people around you.

PSGN vs IgA nephropathy how to tell them apart in an exam

Dr. Silva comments on several diagnostic dilemmas where the pathology pattern leads to a plethora of possibilities.

Die membranöse Glomerulonephritis ist die häufigste Ursache für ein nephrotisches Syndrom im Erwachsenenalter. Die klassische Behandlung besteht aus einer konservativen/supportiven Therapie und in schwerwiegenden Fällen aus einer Immunsuppression. In einer neuen Studie wurde nun untersucht, ob Rituximab eine Alternative darstellen könnte, was in dieser Podcast-Folge besprochen wird.

If you naively thought that part 2 of glomerulonephritis would never come and you could spend the rest of your summer wallowing in glorious ignorance of those confusing glomerulonephritidis then you were wrong. Here are the rest of the nephritic … Continue reading →

In this episode I cover glomerulonephritis.If you want to follow along with written notes on glomerulonephritis go to https://zerotofinals.com/medicine/renal/glomerulonephritis/ or the renal section in the Zero to Finals medicine book.This episode covers definitions, diagnoses, types and management of glomerulonephritis. The audio in the episode was expertly edited by Harry Watchman.

This is a podcast article summary of "Fibrillary Glomerulonephritis: Clinicopathologic Features and Atypical Cases from a Multi-Institutional Cohort" by Nicole Andeen, Kelly Smith, and Rupali Avasare, on behalf of themselves and their coauthors.

This is a podcast article summary of "Fibrillary Glomerulonephritis: Clinicopathologic Features and Atypical Cases from a Multi-Institutional Cohort" by Nicole Andeen, Kelly Smith, and Rupali Avasare, on behalf of themselves and their coauthors.

Get your amphora ready to catch some of the golden stuff and see if you have the blood and the protein to raise some nephrologist eyebrows. We’ve heard the requests of the people and taken on GN in an epic … Continue reading →

Pathologystudent.com - A simple summary of glomerulonephritis

Dr. Scott Cohen discusses how patients can manage glomerulonephritis, a group of kidney diseases.

In this episode, Dr. Silva discusses the term focal and how such a simple word has undergone a significant shift in usage over the last century in renal pathology.

In this podcast, Emma van Daalen, summarizes the article, "Predicting Outcome in Patients with Anti-GBM Glomerulonephritis" on behalf of her co-authors.

In this podcast, Emma van Daalen, summarizes the article, "Predicting Outcome in Patients with Anti-GBM Glomerulonephritis" on behalf of her co-authors.

This week on Humerus Hacks we discuss the ins and outs of glomerulonephritis, plus Pokemons, porcupines, and politics on trams! 

Symptoms and treatment of post strep Glomerulonephritis in pediatric patients, and the new demographic that is being effected.

Crescentic glomerulonephritis is characterized by glomerular necrosis. Dying cells release intracellular proteins that act as danger-associated molecular patterns to activate the innate immune system. Previously, we have demonstrated that dying tubular cells release histones, which can kill endothelial cells and activate the toll-like receptor 2/4 (TLR2/4). This drives tubulointerstitial inflammation in septic or post-ischemic acute kidney injury (AKI). Furthermore, other groups have also reported that extracellular histones cause organ damage during acute lung injury, stroke, peritonitis and retinal dysfunction, and that blocking extracellular histones represents a beneficial approach during the disease progression. In this thesis, we investigated whether extracellular histones can elicit similar pathogenic effects during necrotizing glomerulonephritis. To do so, we used an animal model based on the necrotizing type of severe glomerulonephritis. Necrotic glomerulonephritis was induced in mice by a single intravenous injection of 100µl sheep anti-GBM antiserum. The impact of histone neutralization was studied by using an antibody isolated from the BWA-3 clone, which had the capacity to neutralize released extracellular histones in-vivo and in-vitro. After 7 days, mice were sacrificed and kidneys were collected for further data analysis. Proteinuria was assessed in spot urine samples. Anti-GBM treated mice showed increased proteinuria (albumin/creatinine ratio), plasma creatinine and BUN levels. This was associated with a reduced number of podocytes, increased crescentic glomeruli and the infiltration of neutrophils and macrophages into the kidney. Interestingly, neutralization of extracellular histones significantly reduced proteinuria leading to less podocyte damage. This was linked to an improved renal function defined by lower plasma creatinine and BUN levels, and with a decrease in neutrophil and macrophage infiltration and activation in kidney. Histone blockade also significantly reduced renal mRNA expression of TNF-α and fibrinogen in the glomerular capillaries, which was associated with less glomerulosclerosis, crescents and tubular atrophy. In-vitro studies demonstrated that extracellular histones and NETs-related histones kill glomerular endothelial cells, podocytes and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as anti-histone IgG, activated protein C or heparin prevented this cytotoxic effect. Stimulation of BMDCs with histones upregulated the expression of the activation marker including MHC-II, CD48, CD80 and CD86 significantly as well as increased the production of TNF-α and IL-6. It has been previously reported by others including us that in biopsies from patients with ANCA-associated vasculitis showed an over-expression of the TLR2/4 receptor compared to the healthy glomeruli. Histone toxicity on glomeruli ex-vivo was also dependent on the TLR2/4 receptor axis given that the lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-GBM glomerulonephritis involved NET formation and vascular necrosis, while blocking NET formation via PAD inhibitor or pre-emptive anti-histone IgG injection significantly reduced all parameters of glomerulonephritis including vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment and activation of glomerular leukocytes, and glomerular crescent formation. Finally, to evaluate histones as a therapeutic target, mice with established glomerulonephritis were treated with three different histone-neutralizing agents such as anti-histone IgG, recombinant activated protein C and/or heparin. Interestingly, all agents were equally effective in abrogating severe glomerulonephritis, while combination therapy had no additive effect. In summary, the results of this thesis indicate that NET-related histones released during glomerulonephritis elicit cytotoxic and immunostimulatory effects and that neutralizing extracellular histones, therefore, represents a potential therapeutic approach when applied during already established glomerulonephritis.

Dr. Caster is an Assistant Professor with the University of Louisville in the division of Nephrology. In this lecture she discusses glomerulonephritis. Her faculty profile can be found here: http://www.uoflphysicians.com/1659402287-dawn-caster  

A small overview of Glomerulenephitis

Obwohl die immunstimulatorischen Effekte viraler Nukleinsäursen, wie auch IFN -α und IFN-β, während Virusinfektionen eine wichtige Rolle spielen, ist wenig über ihre Funktion bei viraler Glomerulonephritis, wie beispielsweise HIV Nephropathie, bekannt. Virusinfektionen aktivieren, vor allem mittels IFN-α und IFN-β Produktion eine systemische antivirale Immunantwort. Es wurde gezeigt, dass diese inflammatorischen Zytokine einen pleiotropen immunmodulatorischen Effekt auf renale Mesangialzellen ausüben, was direkt zu glomerulären Krankheiten führt. Aber es ist bisher nicht bekannt, ob die viralen Nukleinsäuren und Typ I IFN einen Effekt auf die glomerulären Epithelzellen haben. (z.B. Podozyten und PECs). Um den Effekt von Nukleinsäuren auf Podozyten und PECs zu erforschen, stimulierten wir diese Zellen mit synthetischen dsDNA-(poly-dAdT) Komplexen mit lipofectamine, um eine virale Infektion zu imitieren. Wir haben herausgefunden, dass dsDNA stetig viele IFN-stimulierte Gene in Podozyten und PECs induziert. Desweitern haben wir herausgefunden, dass dsDNA die PECs Proliferation mindert und die CD24+/CD133+PECs Differenzierung zu ausgereiften Podozyten inhibiert. Um unsere Hypothese, dass deis aufgrund von der Sekretion von IFN-α und IFN-β passiert ist, zu bestätigen, haben wir den Effekt von diesen anitviralen Zytokinen auf PECs- und Podozyten-Homöostase etabliert. Wir haben herausgefunden, dass beide IFNs stetig Podozyten und PECs dazu anregen, stetig mehrere IFN-stimulierte Gene zu exprimieren. Trotzdem hat nur IFN-β das Podozytensterben induziert und die Permeabilität der Podozyten-Monolayer erhöht. In der Adriamycin-induzierter Nephropathie bei SCID Mäusen haben Injektionen mit IFN-α oder IFN-β die Proteinurie, den Makrophagen Influx und die Glomerulosklerose verstärkt. Trotzdem induziert nur IFN-β das mitotische Podozytensterben (katastrophale Mitose), welches zu einer reduzierten Podozytenanzahl führt. Wir haben führt, dass IFN-α einen Zellzyklusarrest in-vivo bei PECs induziert, der zur glomerulären Schädigung führt. Balb/c Mäuse, die Adriamycin gespritzt bekommen haben und täglich mit IFN-α und IFN-β behandelt wurden zeigten einen aggravierten Phänotyp mit vermehrter Proteinurie. Im Gegensatz zu dem, was an Studien in SCID Mausen gezeigt wurde, war der Effekt auf die Proteinurie nach IFN-α Behandlung prominenter bei Balb/c Mäusen, verglichen mit IFN-β. Deshalb haben Typ I IFNs einen deutlichen Effekt auf Podozyten und Parietalzellen. Zusammen fördern die Typ I IFNs die Glomerulosklerose durch verstärkten Untergang der Podozyten sowie durch Unterdrückung ihrer Regeneration aus Vorläuferzellen.

The causes, clinical presentation and pathology of nephritic syndrome and post infectious glomerulonephritis.

Thu, 24 Jan 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15577/ https://edoc.ub.uni-muenchen.de/15577/1/Haegele_Holger.pdf Hägele, Holger ddc:610, ddc:600, Medizinische Fakultät

Thu, 18 Oct 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15001/ https://edoc.ub.uni-muenchen.de/15001/1/Neumann_Iris.pdf Neumann, Iris

Die von intrinsichen renalen Zellen und infiltrierenden Leukozyten exprimierten Zytokine sind zentrale Vermittler entzündlicher Nierenerkrankungen. Tumor Nekrose Faktor-α (TNF) ist ein solches proinflamatorisches Zytokin, das in der glomerulären Entzündungsreaktion involviert ist. Die funktionelle Rolle von TNF wurde in Tiermodellen der Glomerulonephritis belegt. Die biologischen Effekte von TNF werden durch die beiden funktionell eigenständigen TNF-Rezeptoren TNFR1 (CD120a) und TNFR2 (CD120b) vermittelt. Neuere Daten zeigen, dass in Modellen einer Immunkomplex-Glomerulonephritis wie der nephrotoxische Serumnephritis die beiden TNF-Rezeptoren in vivo unterschiedliche Funktionen bei der glomerulären Entzündung vermitteln können. Der vorliegenden Arbeit liegt die Hypothese zugrunde, dass Tnfr1 und Tnfr2 unterschiedliche inflammatorische TNF-Effekte in Glomeruli vermitteln. Daher war das Ziel dieser Arbeit, Expression und Funktion der beiden TNF-Rezeptoren in Maus-Glomeruli zu charakterisieren und die Tnfr-abhängig exprimierten Entzündungsmediatoren in Maus-Glomeruli zu identifizieren. Aufbauend auf den Ergebnissen dieser Arbeit könnten selektive, Tnfr-spezifische Therapien zur Hemmung der glomerulären Entzündungsreaktion entwickelt werden. Zudem wurde in dieser Arbeit die funktionelle Rolle der beiden TNF-Rezeptoren im MRL/lpr-Mausmodell der Lupusnephritis untersucht, um eine selektive Tnfr-Blockade als mögliche Therapiestrategie zu charakterisieren. Hierfür war eine Rückkreuzung von Tnfr1- und Tnfr2-defizienten C57BL/6J-Mäusen in den MRL/lpr-Hintergrund erforderlich. Um TNF-Rezeptor-1- und 2-vermittelte inflammatorische Signalwege in Glomeruli zu identifizieren wurde die Expression und die Funktion der beiden TNF-Rezeptoren in Mausnieren, in isolierten Glomeruli ex vivo und murinen glomerulären Endothel- und Mesangialzellen in vitro untersucht. In normaler Mausniere konnte eine Tnfr1- und Tnfr2-mRNA- und Protein-Expressionen präferentiell in Glomeruli im Vergleich zum Tubulointerstitium nachgewiesen werden. Die Expression von beiden TNF-Rezeptoren und die TNF-induzierte Induktion von Tnfr2-mRNA-Expression wurde auch in vitro sowohl in murinen glomerulären Endothel- als auch Mesangialzelllinien bestätigt. Die prominente glomeruläre TNF-Rezeptor-Expression korrelierte mit einer konstitutiven glomerulären mRNA-Expression von Adhäsionsmolekülen wie Icam-1, Vcam-1, E- und P-Selektin und Chemokinen wie Ccl2, Ccl3 und Ccl5. Eine intraperitoneale TNF-Injektion induzierte die Expression dieser Mediatoren präferentiell in Glomeruli. Diese in vivo TNF-Exposition führte zu einer raschen glomerulären Akkumulation von Leukozyten einschließlich Neutrophilen und mononukleären Phagozyten, die mittels einer kompartimentspezifischer Durchflußzytometrie analysiert wurden. Um Tnfr-abhängige inflammatorische Effekte in intrinsischen glomerulären Zellen unabhängig von infiltrierenden Leukozyten zu untersuchen, wurde eine Microarray-Gene-Expressionsanalyse an intakten Glomeruli durchgeführt, die aus Wildtyp und Tnfr-defizienten Mäusen isoliert und anschließend mit TNF ex vivo stimuliert wurden. Die meisten TNF-Effekte wurden ausschließlich durch Tnfr1 vermittelt, unter anderem die induzierte mRNA-Expression von Adhäsionsmolekülen, proinflammatorischen Chemokinen, Komplement-Faktoren und proapoptotischen Molekülen. Im Gegensatz dazu fanden wir nur vier Tnfr2-abhängig exprimierte Gene, einschließlich einer kleinen GTPase der Rab-Familie (Rab6b). Diese Ergebnisse wurden durch quantitative RT-PCR-Analysen von TNF-stimulierten Glomeruli und primären Mesangialzellen bestätigt. Weitere Untersuchungen zeigten allerdings auch einen Beitrag von Tnfr2 bei der gesteigerten glomerulären Expression von Adhäsionsmolekülen und Chemokine nach Stimulation mit niedrigen TNF-Konzentrationen auf. Im Gegensatz zur Wildtyp-Kontrolle fehlte in TNF-stimulierten Tnfr1-defizienten Glomeruli die Sekretion verschiedener proinflammatorischer Chemokine beinahe vollständig. Interessanterweise war die Proteinexpression auch in Tnfr2-defizienten Glomeruli signifikant herunterreguliert. Folglich sind die meisten inflammatorischen TNF-Effekte in Glomeruli via Tnfr1 durch die induzierte Expression von proinfammatorischen Mediatoren wie Adhäsionsmolekülen und Chemokinen vermittelt. Darüber hinaus dürfte Tnfr2 zu dieser inflammatorischen Antwort beitragen, wenn Glomeruli niedrigen TNF-Konzentrationen ausgesetzt sind. Ferner scheint Tnfr2 posttranskriptionell die Chemokinsekretion in Glomeruli nach einer TNF-Exposition zu beeinflussen, möglicherweise durch die Tnfr2-abhängig exprimierte Rab GTPase Rab6b, die am intrazellulären Transport und der Sekretion von inflammatorischen Molekulen beteiligt sein könnte. In Bezug auf Tnfr-spezifische, anti-inflammatorische Therapien weisen die hier präsentierten Ergebnisse somit darauf hin, dass eine selektive Tnfr1-Blockade eine glomeruläre, insbesondere durch Granulozyten und Makrophagen vermittelte Entzündung verbessern könnte, möglicherweise bei geringer Hemmung immunregulatorischer und antimikrobieller Funktionen von TNF, die redundant durch Tnfr2 vermittelt werden könnten. Dagegen erscheint aufgrund der erhobenen Daten im MRL/lpr-Mausmodell eine Blockade von TNF oder beider Rezeptoren bei der Lupusnephritis, in der glomeruläre Neutrophileninfiltrate keine entzündliche Rolle spielen, weniger erfolgversprechend. Gleichzeitig weisen die vorliegenden Ergebnisse auf eine immunsuppressive, die systemische Immunreaktivität beim SLE begrenzende Funktion von Tnfr2 hin.

Eine Glomerulonephritis kann durch eine virale Infektion verschlechtert werden, sie kann aber auch erst durch diese entstehen. Die Erkennung der viralen Bestandteile erfolgt über Pathogenerkennungsrezeptoren, wie beispielweise Toll-like Rezeptoren und RIG-like Rezeptoren. Die Hypothese der vorliegenden experimentellen Arbeit war, dass die nierenspezifischen Podozyten Pathogenerkennungsrezeptoren besitzen, die pathogen-assoziierte molekulare Muster erkennen und daraus Zytokine und antivirale Typ-I Interferone produzieren. Hierbei könnten Podozyten zu der Entstehung bzw. Veschlechterung einer virusassoziierten Glomerulonephritis beitragen. Murine Podozyten exprimieren, mit Ausnahme des Toll-like Rezeptors 8, alle bis dato bekannten Toll-like Rezeptoren (TLR-1 bis -11) in verschiedener Ausprägung. Sie exprimieren außerdem die zytosolische Rezeptoren RIG-1, MDA-5, DAI sowie deren Adaptermolekül IPS-1. Die Aktivierung dieser Rezeptoren verursacht die Produktion von Zytokinen und Typ-I Interferonen. Um die intrazelluläre Aufnahme der Nukleinsäuren zu gewährleisten, wurden diese mit kationischen Lipiden komplexiert. Dieser Vorgang wurde durch Cytochalasin D, Chlorpromazin und Methyl-β-Cyclodextrin unterbrochen. Daraufhin ergeben sich die Phagozytose, die Clathrin-abhängige Endozytose und die Caveolae-vermittelte Endozytose als mögliche Transportmechanismen. Das Adaptorprotein MyD88 zeigte bei Podozyten keine Bedeutung für die Nukleinsäureaufnahme in die Zelle zu besitzen. Die Stimulation von Podozyten mit Typ-I Interferonen veranlasste die Produktion von großen Mengen an Interleukin-6 und führte zu einer starken Expression von Pathogenerkennungsrezeptoren sowie proinflammatorischen Zytokinen auf Transkriptionsebene. Eine autokrin-parakrine Aktivierung der Podozyten durch ausgeschüttete Typ-I Interferone konnten wir ausschließen. Weder die Durchlässigkeit für Albumin noch die Viabilität der Zellen wurde durch die Aktivierung von Pathogenerkennungsrezeptoren beeinflusst. Eine Funktionseinschränkung der Podozyten nach Stimulation der TLRs oder RLRs im Sinne eines direkten Einflusses auf die Permeabilität oder die Fußfortsatzzahl fand sich nicht, jedoch zeigten Podozyten eine vermehrte Zytokinproduktion, was zur glomerulären Entzündung bei viraler Glomerulonephritis beitragen könnte.

IL-1β and IL-18 are proinflammatory cytokines that contribute to renal immune complex disease, but whether IL-1β and IL-18 are mediators of intrinsic glomerular inflammation is unknown. In contrast to other cytokines the secretion of IL-1β and IL-18 requires a second stimulus that activates the inflammasome-ASC-caspase-1 pathway to cleave pro-IL-1β and -IL-18 into their mature and secretable forms. As the NLRP3 inflammasome and caspase-1 were shown to contribute to postischemic and postobstructive tubulointerstitial inflammation, we hypothesized a similar role for NLRP3, ASC, and caspase-1 in glomerular immunopathology. This concept was supported by the finding that lack of IL-1R1 reduced antiserum-induced focal segmental necrosis, crescent formation, and tubular atrophy when compared to wildtype mice. Lack of IL-18 reduced tubular atrophy only. However, NLRP3-, ASC- or caspase-1-deficiency had no significant effect on renal histopathology or proteinuria of serum nephritis. In vitro studies with mouse glomeruli or mesangial cells, glomerular endothelial cells, and podocytes did not reveal any pro-IL-1β induction upon LPS stimulation and no caspase-1 activation after an additional exposure to the NLRP3 agonist ATP. Only renal dendritic cells, which reside mainly in the tubulointerstitium, expressed pro-IL-1β and were able to activate the NLRP3-caspase-1 axis and secrete mature IL-1β. Together, the NLRP3-ASC-caspase-1 axis does not contribute to intrinsic glomerular inflammation via glomerular parenchymal cells as these cannot produce IL-1β during sterile inflammation.

The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated recruitment of leukocytes. Both of these mechanisms are known to be involved in autoimmunity and autoimmune tissue injury, e.g. in systemic lupus erythematosus, but a contribution of PTX3 is hypothetical. To evaluate a potential immunoregulatory role of PTX3 in autoimmunity we crossed Ptx3-deficient mice with Fas-deficient (lpr) C57BL/6 (B6) mice with mild lupus-like autoimmunity. PTX3 was found to be increasingly expressed in kidneys and lungs of B6lpr along disease progression. Lack of PTX3 impaired the phagocytic uptake of apoptotic T cells into peritoneal macrophages and selectively expanded CD4/CD8 double negative T cells while other immune cell subsets and lupus autoantibody production remained unaffected. Lack of PTX3 also aggravated autoimmune lung disease, i.e. peribronchial and perivascular CD3+ T cell and macrophage infiltrates of B6lpr mice. In contrast, histomorphological and functional parameters of lupus nephritis remained unaffected by the Ptx3 genotype. Together, PTX3 specifically suppresses autoimmune lung disease that is associated with systemic lupus erythematosus. Vice versa, loss-of-function mutations in the Ptx3 gene might represent a genetic risk factor for pulmonary (but not renal) manifestations of systemic lupus or other autoimmune diseases.

Non-CpG-DNA and 3P-RNA activated mesangial cells to produce inflammatory cytokines and type 1 interferons in TLR-independent manner. Both ligands induced similar gene expression patterns in mesangial cells. This data unravelled the existence of TLR-independent pathways and production of type1 interferons in mesangial cells. These results substantiate the idea that, immune complexes that are associated with nucleic acids can activate glomerular cells via TLR-independent manner, which leads to glomerular inflammation. Furthermore, exposure of non-CpG-DNA and 3P-RNA in MRLlpr/lpr mice aggravated the disease pathology in different manner. Even though 3P-RNA and non-CpG-DNA induced similar gene expression in mesangial cells but in vivo both ligands aggravated the disease in different fashion. 3P-RNA induced type I IFN signaling and decreased the number of regulatory T cells while non-CpG-DNA induced plasma cell expansion, lymphoproliferation and splenomegaly. However, both ligands induced the production of dsDNA autoantibodies and increased the glomerular deposition of IgG. These data suggest that viral 3P-RNA and non-CpG-DNA differently modulate autoimmunity but still both aggravate autoimmune tissue injury by activating non-immune cells at the tissue level

Es ist bereits bekannt, dass akute Infektionen zur Verschlechterung einer vorbestehenden Glomerulonephritis führen können. Dies ist zum Beispiel bei der Lupusnephritis, der IgA-Nephropathie oder der renalen Vaskulitis der Fall (mesangioproliferative Glomerulonephritiden). Chronische virale Infektionen (z.B. Hepatitis C) können sogar eine de novo Glomerulonephritis auslösen. Hierbei handelt es sich um eine Immunkomplex-Glomerulonephritis, die durch die Bildung von Immunkomplexen aus eindringendem Antigen und daraufhin gebildetem Antikörper entsteht. Die Immunkomplexe werden über den Fc-Teil des Antikörpers erkannt. Ob die viralen Komponenten dieser Komplexe auch direkt erkannt werden und von welchen Zellen ist unbekannt. Neben der Bildung von Immunkomplexen spielt die Produktion von Interferonen eine wichtige Rolle bei der Entstehung von virusassoziierten Glomerulonephritiden. Die Aktivierung der systemischen antiviralen Immunität führt zur systemischen Interferonfreisetzung. Es wird angenommen, dass die meisten Zellen Typ I-Interferone produzieren können, wenn sie viral infiziert werden. So kann beispielsweise die TLR-3- vermittelte Erkennung viraler dsRNA in den Inselzellen des Pankreas über lokale IFN-a-Produktion eine autoimmune Inselzellzerstörung auslösen. Dahingegen ist unklar, ob lokal produzierte Typ I-Interferone zur Entstehung von irusassoziierten Glomerulonephritiden beitragen können. Wurde Mäusen virale dsRNA injiziert, gelangte diese zu den glomerulären Mesangialzellen. Mesangialzellen besitzen als einzigen nukleinsäurespezifischen Toll-like Rezeptor den TLR-3 und produzieren auf Stimulation durch virale dsRNA hin Interleukin-6 und CCL2. Ob dieser Effekt über den endosomalen TLR-3 oder über zytosolische dsRNA-Rezeptoren abläuft und ob Mesangialzellen überhaupt Interferone produzieren können, ist allerdings noch unklar. Unsere Hypothese ist, dass Mesangialzellen virale RNA sowohl TLR-abhängig als auch TLR-unabhängig erkennen können und dass die virale RNA daraufhin ein angeborenes antivirales Antwortprogramm, einschließlich der Produktion von Typ I-Interferonen, in glomerulären Mesangialzellen aktiviert.

Thu, 7 May 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/10160/ https://edoc.ub.uni-muenchen.de/10160/1/Lichtnekert_Julia.pdf Lichtnekert, Julia

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Thu, 4 Dec 2003 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/1711/ https://edoc.ub.uni-muenchen.de/1711/1/Frink_Michael.pdf Frink, Michael ddc:610, ddc:600, Medizinis