POPULARITY
8 episodes with glomerular
3 episodes with glomerular
3 episodes with glomerular
3 episodes with glomerular
3 episodes with glomerular
2 episodes with glomerular
2 episodes with glomerular
3 episodes with glomerular
2 episodes with glomerular
In this episode, we review the high-yield topic of Glomerular Filtration Rate (GFR) from the Renal section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets Linkedin: https://www.linkedin.com/company/medbullets
Jai Radhakrishnan, MD, MS / Ladan Zand, MD - Investigating Novel Approaches and Unmet Needs in the Management of Glomerular Diseases
Jai Radhakrishnan, MD, MS / Ladan Zand, MD - Investigating Novel Approaches and Unmet Needs in the Management of Glomerular Diseases
Jai Radhakrishnan, MD, MS / Ladan Zand, MD - Investigating Novel Approaches and Unmet Needs in the Management of Glomerular Diseases
Jai Radhakrishnan, MD, MS / Ladan Zand, MD - Investigating Novel Approaches and Unmet Needs in the Management of Glomerular Diseases
Lab Values Podcast (Nursing Podcast, normal lab values for nurses for NCLEX®) by NRSNG
Overview Urinalysis Color & Clarity Protein RBC WBC Glucose Specific gravity Ketones pH Bilirubin/Urobilinogen Nursing Points General Normal value range Color & Clarity Normal – Yellow Other colors Drug interactions Propofol – green Methylene blue – blue/green Trauma Red/Brown Liver failure Brown/tea colored Clear – Normal Cloudy Cell or contaminant related Turbid Severe presence of cells (WBC, RBC) pH ~6 Changes in body condition can change pH Metabolic acidosis/alkalosis Protein 0-trace Glomerular permeability/infection RBC 0-2 Bleeding Trauma/injury below kidneys WBC Negative Sepsis/Infection/UTI Glucose Negative Diabetes Ketones Negative Presence of ketones can indicate endocrine disease like Diabetes Urine Specific Gravity 1.010-1.030 Facilities vary Ability to concentrate urine Hydration Overhydration Decreased USG Dehydration Increased USG Diabetes insipidus Causes increased diuresis SIADH (Syndrome of Inappropriate Antidiuretic Hormone) Causes decreased diuresis Bilirubin/Urobilinogen Negative Presence indicates potential liver problems Nursing Concepts Lab Values Elimination
The important question is when to suspect vasculitis based on clinical presentation? We discuss differentials and workup (with emphasis on ANCA positivity or negativity or markers of Glomerular involvement) as well as management options and complications (including Mono-neuritis multiplex) for most common classes of vasculitides including Medium-size & Small - vessel Vasculitides including Polyarteritis Nodosa (including updated 3/10 Diagnostic criteria of American College of Rheumatology), Buerger's Disease (Thromboangiitis Oblisterans) Wegener's Granulomatosis, Microscopic Polyangiitis, Churg-Strauss.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538276v1?rss=1 Authors: Yasuda, H., Fukusumi, Y., Zhang, Y., Kawachi, H. Abstract: Adaptor protein 14-3-3s have isoform-specific binding partners and roles. We reported 14-3-3{beta} interacts with FKBP12 and synaptopodin to maintain the structure of actin fibers in podocytes. However, differential roles of 14-3-3 isoforms in kidneys are unclear. Herein, we showed that 14-3-3{beta} was dominantly co-localized with FKBP12 in foot processes and was partially co-localized with Par3 at slit diaphragm in podocytes. 14-3-3{beta} interacted with Par3, and FKBP12 bound to 14-3-3{beta} competitively with Par3. Although deletion of 14-3-3{beta} enhanced the interaction of Par3-Par6, it altered actin fiber structure and processes. 14-3-3{beta} and synaptopodin were downregulated in podocyte injury models. 14-3-3{sigma} in podocytes interacted with vimentin in primary processes but not with the actin-associated proteins in foot processes. Deletion of 14-3-3{sigma} altered vimentin fiber structure and processes. 14-3-3{sigma} and vimentin were upregulated in the early phase of podocyte injury models but were decreased in the end stage. Together, the precise localization of 14-3-3{beta} at actin cytoskeleton plays a role in maintaining foot processes and Par complex in podocytes. 14-3-3{sigma} at vimentin cytoskeleton is essential for maintaining primary processes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Get a free nursing lab values cheat sheet at NURSING.com/63labs Overview Urinalysis Color & Clarity Protein RBC WBC Glucose Specific gravity Ketones pH Bilirubin/Urobilinogen Nursing Points General Normal value range Color & Clarity Normal – Yellow Other colors Drug interactions Propofol – green Methylene blue – blue/green Trauma Red/Brown Liver failure Brown/tea colored Clear – Normal Cloudy Cell or contaminant related Turbid Severe presence of cells (WBC, RBC) pH ~6 Changes in body condition can change pH Metabolic acidosis/alkalosis Protein 0-trace Glomerular permeability/infection RBC 0-2 Bleeding Trauma/injury below kidneys WBC Negative Sepsis/Infection/UTI Glucose Negative Diabetes Ketones Negative Presence of ketones can indicate endocrine disease like Diabetes Urine Specific Gravity 1.010-1.030 Facilities vary Ability to concentrate urine Hydration Overhydration Decreased USG Dehydration Increased USG Diabetes insipidus Causes increased diuresis SIADH (Syndrome of Inappropriate Antidiuretic Hormone) Causes decreased diuresis Bilirubin/Urobilinogen Negative Presence indicates potential liver problems Nursing Concepts Lab Values Elimination
To receive up to 1.0 CME/CE credit please complete the evaluation and request form here: https://www.ceconcepts.com/igan-ee-podcastThis activity will take learners on a deep dive into the pathophysiology of proteinuric glomerular disease, with an incisive focus on IgA nephropathy (IgAN). Expert faculty will review the totality of emerging evidence for novel therapeutics in IgAN, including an appraisal of consensus guidelines and regulatory updates. Finally, the session will conclude with a case-based segment wherein attendees will get to apply the principles they've learned to real-world clinical scenarios.Supported through an independent educational grant from Travere.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.31.526422v1?rss=1 Authors: Licht, T., Yunerman, M., Maor, I., Lawabny, N., Oz Rokach, R., Mizrahi, A., Rokni, D. Abstract: The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortex in these mice responded to odors normally and its neural activity sufficed to decode odor identity. We analyzed the circuitry that supports olfactory function in these mice. We found that sensory neurons express the full repertoire of olfactory receptors and their axons project primarily to the rudimentary OB, but also ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced and the morphology of their dendrites was abnormal, extending over larger regions within the OB. Glomerular organization was lost. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements that are believed to be essential for olfaction, and may explain the retention of olfaction in humans with degenerated OBs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In this episode, we review the high-yield topic of Glomerular Filtration Barrier from the Renal section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://anchor.fm/medbulletsstep1/message
Looking for more information on this topic? Check out the Regulation of Renal Blood Flow and Glomerular Filtration brick. If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts. It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Twitter: https://twitter.com/mesage_hub Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including over 800 Rx Bricks. After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.
Reversing chronic kidney disease (CKD) with a ketogenic lifestyle. Dr. Nally's Ketogenic Dietary Information: https://www.docmuscles.com/dietpage/ Show References: 1. Siperstein MS, Unger RH, Madison LL. “Further Electron Microscopic Studies of Diabetic Microagniopathy.” Early Diabetes: Advances in Metabolic Disorders, sup 1. New York: Academic Press, 1972, p261-271. 2. Nasr SH, D'Agati VD. “Nodular glomerulosclerosis in the nondiabetic smoker.” J Am Soc Nephrol. 2007;18(7):2032. 3. Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, Mobbs CV (2011) Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 6(4): e18604. doi:10.1371/journal.pone.0018604 4. Kundu S, Hossain KS, Moni A, Zahan MS, Rahman MM, Uddin MJ. Potentials of ketogenic diet against chronic kidney diseases: pharmacological insights and therapeutic prospects. Mol Biol Rep. 2022 Oct;49(10):9749-9758. doi: 10.1007/s11033-022-07460-8. Epub 2022 Apr 20. PMID: 35441940. 5. Rojas-Morales P, León-Contreras JC, Sánchez-Tapia M, Silva-Palacios A, Cano-Martínez A, González-Reyes S, Jiménez-Osorio AS, Hernández-Pando R, Osorio-Alonso H, Sánchez-Lozada LG, Tovar AR, Pedraza-Chaverri J, Tapia E. A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation. Life Sci. 2022 Jan 15;289:120227. doi: 10.1016/j.lfs.2021.120227. Epub 2021 Dec 16. PMID: 34921866. 6. Jolliffe N, Smith HW. The excretion of urine in the dog. I. The urea and creatinine clearances on a mixed diet. Am J Physiol 98: 572–577, 1931. 7. Parving HH, Noer J, Kehlet H, Mogensen CE, Svendsen PA, Heding L. The effect of short-term glucagon infusion on kidney function in normal man. Diabetologia 13: 323–325, 1977pmid:334617. 8. Fioretto P, Trevisan R, Velussi M, Cernigoi A, De Riva C, Bressan M, Doria A, Pauletto N, Angeli P, De Donà C, et al. Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate. J Clin Endocrinol Metab. 1987 Aug;65(2):331-8. doi: 10.1210/jcem-65-2-331. PMID: 3298305. #CKD #ChronicKidneyDisease #Kidney #diabeticNephropathy #Diabetes #LeadFolloworGetOutOrMyWay #JustKeepEsterifying #Ketogenic #Keto #KetogenicLifestyle #Carnivore #DrAdamNally #DocMuscles #DocMusclesLive #DocTalk #DocsWhoLift #LiftRunShoot #DocMusclesLife YouTube.com/drnally/.
The Journal RETINA is devoted exclusively to diseases of the retina and vitreous. These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.
Looking for more information on this topic? Check out the Glomerular Diseases: Foundations and Frameworks brick. If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts. It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Twitter: https://twitter.com/mesage_hub Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including over 800 Rx Bricks. After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.
Dr. Centor discusses the quantification of inaccuracy in estimation of glomerular filtration rate with Dr. Tariq Shafi.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.30.510181v1?rss=1 Authors: Gruber, L., Cantera, R., Pleijzier, M. W., Hansson, B. S., Rybak, J. Abstract: To manage the great complexity of detecting and identifying olfactory cues, the insect olfactory system has evolved two main strategies: combinatorial coding and specialized, narrowly tuned olfactory pathways. In combinatorial coding, odorants are encoded by activation of multiple, broadly tuned olfactory sensory neurons that innervate distinct sets of glomeruli. In specialized olfactory pathways, information regarding a single or a few odorants is processed in a discrete, narrowly tuned circuit within a dedicated glomerulus. Here, we compared the narrowly tuned glomerulus DA2 with the broadly tuned glomerulus DL5 at the ultrastructural level, by using volume based focused ion beam scanning electron microscopy. We provide a detailed analysis of neuronal innervation, synaptic composition as well as a circuit diagram of the major glomerular cell types: olfactory sensory neurons (OSNs), uniglomerular projection neurons (uPNs) and multiglomerular neurons (MGNs). By comparing our data with a previously mapped narrowly tuned glomerulus (VA1v), we disclose putative generic features of narrowly tuned glomerular circuits: a high density of neuronal fibers and synapses, a low degree of sensory lateralization, strong axo-axonic connections between OSNs as well as dendro-dendritic connections between uPNs, and a low degree of presynaptic inhibition at the OSN axons. We also show a unique property of the large uPN dendrite in DL5, which forms substantial amount of autapses. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Host: Javed Butler, MD, MBA, MPH Guest: Tariq Shafi, MD Although population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate are well-known, the individual-level differences are not. So what clinical implication can this have for our patients? Learn about these fresh findings with Dr. Javed Butler and Dr. Tariq Shafi, the John D. Bower Director of the Division of Nephrology and Professor of Medicine at the University of Mississippi Medical Center. Together, they discuss a recent study from the Annals of Internal Medicine that explored this topic.
References Dr Guerra lecture notes Front. Endocrinol., 14 October 2014. Sci Rep. 2020; 10: 21628. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Looking for more information on this topic? Check out the Physiology of Glomerular Filtration brick. If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts. It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks. After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.
In this podcast, Dr. Kim Thielen, a nephrologist/kidney specialist with Minnesota Kidney Specialists joins us today to continue part 2 of our discussion on acute kidney injury, as we wade further "into the weeds" discuss intrinsic renal disease. This episode will break down hallmark urinary findings and further subdivide intrinsic concerns into bland, nephrotic and nephritic, various causes, and treatment. Enjoy the podcast! Objectives: Upon completion of this podcast, participants should be able to: State the 3 types of urinary analysis findings related to instrinic acute kidney injury. Describe etiology of presentation of each type of intrinsic acute kidney injury. CME credit is only offered to Ridgeview Providers & Allied Health Staff for this podcast activity. Complete and submit the online evaluation form, after viewing the activity. Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks. You may contact the accredited provider with questions regarding this program at rmccredentialing@ridgeviewmedical.org. To receive continuing education credit for this activity - click the link below, to complete the activity's evaluation. CME Evaluation (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.) DISCLOSURE ANNOUNCEMENT The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition; and are property/rights of Ridgeview Medical Center & Clinics. Any re-reproduction of any of the materials presented would be infringement of copyright laws. It is Ridgeview's intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker's outside interest may reflect a possible bias, either the exposition or the conclusions presented. Ridgeview's CME planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. Thank-you for listening to the podcast. SHOW NOTES: *See the attachment for additional show information. Intrinsic Kidney Injuries: Urinary analysis findings- Bland Urine: no protein - Nephrotic: protein - Nephritic: protein and blood Hallmark Urinary Findings: Casts - Tamm Horsfall Protein : Mucoprotein made by tubular epithelial cells that precipitate out and congeal to form casts on whatever is in the cells at the time. (i.e. RBCs, WBCs, tubular debris) Bland Urine States- Crystalline Induced Renal Injury: obstruction and infllamatory response - Uric Acid Neuropathy (Most common) - Cancers, lymphomas, etc. - Drugs: acyclovir, methotrexate, protease inhibitors, etc. - Toxins: Ethylene glycol - Bland Urine Disease states: results from injury to tubules, instertim or pre glomerular blodd vessels, not the filters of the kidney - Interstital Nephritis - Hallmark: pyuria and WBC casts - Biopsy: inflammatory infiltrate - Causes: viral, PPIs, Adenover, mizalamin, etc., Checkpoint inhibitors - Acute Tubular Necrosis - Hallmark: tubular epithelial cell cast - Granular: (course or fine) diagnostic of ATN - Biopsy: denuded dilated tubular cells - Causes: #1: Ischemia; toxins, drugs, contrast dye; pigment injury. myoglobin - What about contrast dye? - Categorized under ATN - Per Dr. Thielen, plays a role, but injury is not solely dependent on dye alone. - Hepatorenal Syndrome: ischemic injury to the kidney due to unopposed vasocontstriction - Ace inhibitors cause unopposed efferent vasoconstriction + nonsteroidals cause unposed afferent vasoconstriction = no glomerular perfusion pressure - Multiple Myeloma - Hallmark: Light chain cast nephropathy or myeloma kidney - Light chains precipitate out causing obstruction, inflammatory response and causes tubular damage - Presentation: older possibly with anemia, bone pain and elevated creatinine with a bland urine. - Protein to creatinine ratio: + for protein (non albumin) - Dipstick: (which measures for albumin and not light chains) will be negative for protein aka bland urine - Hypertensive Nephrosclerosis - Small vessel vascular disease - Blood vessels prematurely atherosclerosis causing glomerular drop out and scarring of the interstim - Scleroderma - Limited cutaneous systemic sclerosis - Diffuse cutaneous systemic sclerosis: 60-80% have renal injury from disease state itself - FANA positive - Concern for Scleroderma Renal Crisis = medical emergency - AKI, moderate to severe HTN and bland urine - Uncontrolled accumulation of collage, thickens vascular walls, narrowing and renal ischemia - Occurs in 10-15% of those with Diffuse Cutaneous Systemic sclerosis and happens early in disease - Left untreated: renal failure in 1-2 months and death in 1 year - Treatment: ACE Inhibitor Nephrotic Urine States - Urine protein: albumin excretion greater than 3.5g in 24 hours - Nephrotic Syndrome: - Present with 3 things (nephrotic range protein, hypoalbuminemia, peripheral edema) - Hyperlipidemia: due to increased hepatic lipogenesis - Increased risk of renal disease and arthroscleratic - Venous thrombotic disease: - Loose proteins other than albumin and develop a hypercoagulale state - Renal and peripheral venous thrombosis - Lipiduria (forms fatty casts, looks like a latese cross under microscope) -Pathophysiology or nephrotic syndrome - Glomerular capillary wall - 3 layers that work as a glomerular filtration and responsible in the filtration between blood and urine - Fenestrated Capillary Enothelial cells (fenestrations allow plasma through to the basement membrane) - Glomerular Basement Membrane (maintains glomerular filtration barrier; negatively charged, repels albumin) - Epithelium: Podocytes (Have highly specialized foot processes that connect and form slit diaphragms; Slit diaphragm important for the efficient flow of small solute and water) - Anything that messes with any of these layers: nephrotic proteinuria - Nephrotic Disease States: - Biopsy: anyone with nephrotic proteinuria (besides diabetics) 1) Light microscopy: high overview 2) Immunofluorescens: looks for nephritic component and identif immunce complexes 3) Electron microscopy: (EM) helps look at the ultrastructure and better identify immune deposits - Diabetic nephropathy - Leading cause of kidney disease in U.S. and western society - Responsible for 30-40% of all ESRD causes - Hyperglycemia: produces inflammatory responses, oxidative stress, and injures the podocytes and deposits that charge and affect the ability of the kidney to filter. - Amyoidosis - Organize into betapleted sheets and produce spikes of the capillary uniion and poke through the GF membrane - Easily identified by apple green birefringence on congo red - Terminal illness - Present with HTN, cardiac effects and elevated creatine - Nephrotic Disease states based of histologic appearance - Diagnosed by histologic appearance but does not determine the etiology - Minimal Change Disease - Fairly common - Minimal change under light microscope - EM: podocytes are abnormal, fused, no unique cell-cell junction - Primary: Immune generated circulating facture; alters the cytoskeleton of the podocytes - Secondary - Nonsteriodal - most common cause of secondary minimal change disease - Gama interferon - Hodgkin's lymphoma - Allergy: 30% of minimal change have associate allergy (mechanism unknown) - Presentation - Sudden onset (days to weeks) - Marked edema and hypoablbuminemia - 60% have normal blood pressure, 82% have normal creatinine - Focal Segmental Glomerulosclerosis (FSGS) - primary and secondary - Most common cause idopathic nephrotic syndrome in adults - Primary glomerulonephritis in the US that causes ESRD - Widespread podocyte injury - Primary: circulating factor that messes with regulation of foot process and adhesion to the glomerular basement membrane (afffect all podocytes) - Present with nephrotic syndrome and rapid progression - HTN and elevated creatinine - Secondary: the visceral epithelial cells don't replicate - Nephron loss or obesity or direct foot process injury - Cannot replicate (podocytes), leads to decreased to podo denisty at specific areas (focal injury) - 2/3 of all cases FSGS - Present: with slowly increasing proteinuria and kidney impairment over time - Causes: interferon, bisphosphonates, talc, anabolic steroids - Genetics: gene mutations that encode for the slit diaphragms of the podocytes (affect all podocytes) - Present in Childhood: full blown nephrotic and progress rapidly to ESRD Membranous Nephropathy - Most common cause of nephrotic syndrome in caucasion adults - 80% present with nephrotic but develops more slowly to ESRD - Primary: Major antigen identified - antibody to trans-membrane receptor that is highly expressed on the glomerular podocyte - Secondary: Cancers (lung, breast, GI), Lupus, Thyroiditis, Hep B, Syphilis, Nonsteroidals, Monoclonal Antibodies Nephritic Syndrome - Hematuria and proteinuria - Hematuria: blood from kidney or outside the kidney - Outside the kidney: look the same - Inside the kidney: dysmorphic red cells - Present: - Renal impairment for days to weeks - Edmatous, HTN and look critically ill - Vasculitis, sinusitis, oral ulcers - Pulmonary renal syndrome: short of breath or hemoptysis - Skin changes: bruising , bleeding, purpura - Myalgias and arthritis - Urine: - Hallmark: red blood cell casts (polymorphic red cells) - dipstick + for blood - elevated proteinuria - Biopsy: nephritic and + urine Nephritic Disease States (based on immunofluorescence staining) - Pauci Immune Disease - Ankle vasculitis, common - A paucity (little amount) of immune complexes - See black on imaging - Lab work: check on ANCA and peripheral eosinophils - Anti-GBM Disease - Renal limited, or classic pulmonary renal: Good Pasture's - linear staining of the glomerular basement with anti IGG (looks like a ribbon on a package) - Treat with cytotoxic agents - Immune Complex - Starry sky pattern - Glomerulus looks dotted with stars - Stars = immune complex definition - Diseases: Lupus (FANA), Post Infectious GN, Membranous Proliferative GN - IGA Nephropathy - Most common cause of glomerulonephritis in the world - Presentation: - Peak incidence is the 2nd and 3rd decades of life - 40-50% gross hematuria with upper respiratory and GI illness - Risk Factors for Progression: - younger age or hypertension at time of presentation - > 1g proteinuria - Elevated creatinine at time of presentation Thanks for listening.
Kumar, V., Abbas, A. K., & Aster, J. C. (2015). Robbins y Cotran. Patología estructural y funcional. Elsevier Health Sciences Spain. --- Send in a voice message: https://anchor.fm/las-poderosas-celulas-nk/message
In this episode, we review the high-yield topic of Glomerular Filtration Rate (GFR) from the Renal section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message
Cupom de desconto de 200 reais para o extensivo R3 de clínica médica da medway: SpfVoyBUPX (https://checkout.medway.com.br/vzW8JjIipE/SpfVoyBUPX) Link para o extensivo R3 de clínica médica da medway: https://r3.medway.com.br/clinica-medica/?utm_source=Social&utm_medium=BrandedContent&utm_campaign=ta-de-clinicagem. Iago apresenta um caso repleto de reviravoltas para Rapha e nosso convidado especial Layon Campagnaro que destrincham o raciocínio clínico por trás da síndrome nefrótica e muito mais. Gostou do episódio? Quer se aprofundar mais nos temas de nefro com qualidade e muita didática? Confere o conteúdo do @nefropapers nas redes sociais! Referências - ROVIN, Brad H. et al. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney International, v. 100, n. 4, p. S1-S276, 2021. - Uptodate 2022. Evaluation of proteinuria in pregnancy and management of nephrotic syndrome. Ravi I Thadhani, Sharon E Maynard, Richard J Glassock, Vanessa A Barss, Albert Q Lam - Uptodate 2021. Glomerular disease: Evaluation and differential diagnosis in adults. Jai Radhakrishnan, Richard J Glassock, Brad H Rovin, Albert Q Lam.
Dr. Centor discusses the estimation of glomerular filtration rate with Dr. Neil Powe.
Look Beneath the Surface: An Expert Dive Into Alport Syndrome
In this episode of Look Beneath the Surface: An Expert Dive into Alport Syndrome, Dr George Bakris welcomes Dr Jochen Reiser for a close look at what COL4A genotyping can tell us about the course and impact of Alport syndrome for both patients and their families. Additional resources are available through the Alport Syndrome Foundation at alportsyndrome.org.
Look Beneath the Surface: An Expert Dive Into Alport Syndrome
In the debut episode of Look Beneath the Surface: An Expert Dive into Alport Syndrome, Dr George Bakris is joined by Dr Joshua Zaritsky to discuss the link between inherited genetic defects and the inflammation and fibrosis that drive disease progression in Alport syndrome.
IgA nephropathy is a cause of glomerulonephritis and is the most common chronic glomerular disease in children. Like the name suggests, it is characterised by kidney damage due to IgA (an immunoglobulin) which deposits in complexes in the kidney. The classic presentation is recurrent episodes of macroscopic haematuria a couple of days after the onset of an URTI. About 25% of children will eventually develop end stage renal failure. In this episode, we discuss IgA nephropathy and its pathophysiology, presentation, management and more! Links and resources: Follow us on Instagram @yourekiddingrightdoctors Facebook: https://www.facebook.com/yourekiddingrightpod-107273607638323/ Our email is yourekiddingrightpod@gmail.com Make sure you hit SUBSCRIBE/FOLLOW so you don't miss out on any pearls of wisdom and RATE if you can to help other people find us! (This isn't individual medical advice, please use your own clinical judgement and local guidelines when caring for your patients)
The Elective Rotation: A Critical Care Hospital Pharmacy Podcast
Show notes at pharmacyjoe.com/episode631. In this episode, I’ll discuss whether kinetic GFR equations can be used in patients with shock. The post 631: Can Kinetic Glomerular Filtration Rate Equations Be Used in Patients With Shock? appeared first on Pharmacy Joe.
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode, I will be emphasizing the hand in hand coordination of knowledge and wisdom. To start with, I will tell you the essence of knowledge of Drug elimination kinetics. I will define the topics and areas it covers, what all and why do we need to know it thoroughly!! The beginnings will be stated by defining the subhead for the day and it sounds like 'Drug Clearance". I will first be defining it, then I will give the formula for it. Next, I will be telling you about important implications and noteworthy essence of different aspects, situations and conditions of clearance! What concerns and cautions govern the drug administration? How does the clearance refers to creatinine clearance? All will be made crystal clear. In a way, I will put your brains to exercise for computing the sumtotal value of clearance by knowledge of renal and hepatic clearance. With signature remarks about the values of renal clearance in relation to Glomerular filtration Rate and tubular secretion and before that a few comments about plasma half life, I will be calling it for the day, hope you find a certain meaningful value out of today's convo..,till we chat next, a soft bbyee.... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via https://linktr.ee/ispharmacologydifficult
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode, I will be emphasizing the hand in hand coordination of knowledge and wisdom. To start with, I will tell you the essence of knowledge of Drug elimination kinetics. I will define the topics and areas it covers, what all and why do we need to know it thoroughly!!The beginnings will be stated by defining the subhead for the day and it sounds like 'Drug Clearance". I will first be defining it, then I will give the formula for it. Next, I will be telling you about important implications and noteworthy essence of different aspects, situations and conditions of clearance!What concerns and cautions govern the drug administration? How does the clearance refers to creatinine clearance? All will be made crystal clear. In a way, I will put your brains to exercise for computing the sumtotal value of clearance by knowledge of renal and hepatic clearance. With signature remarks about the values of renal clearance in relation to Glomerular filtration Rate and tubular secretion and before that a few comments about plasma half life, I will be calling it for the day, hope you find a certain meaningful value out of today's convo..,till we chat next, a soft bbyee.... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode, I will be emphasizing the hand in hand coordination of knowledge and wisdom. To start with, I will tell you the essence of knowledge of Drug elimination kinetics. I will define the topics and areas it covers, what all and why do we need to know it thoroughly!!The beginnings will be stated by defining the subhead for the day and it sounds like 'Drug Clearance". I will first be defining it, then I will give the formula for it. Next, I will be telling you about important implications and noteworthy essence of different aspects, situations and conditions of clearance!What concerns and cautions govern the drug administration? How does the clearance refers to creatinine clearance? All will be made crystal clear. In a way, I will put your brains to exercise for computing the sumtotal value of clearance by knowledge of renal and hepatic clearance. With signature remarks about the values of renal clearance in relation to Glomerular filtration Rate and tubular secretion and before that a few comments about plasma half life, I will be calling it for the day, hope you find a certain meaningful value out of today's convo..,till we chat next, a soft bbyee.... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. I will be starting today's episode with a beautiful thought compilation about "Lantern" and the book "Sky Lantern" by Matt Makeloto, its a lovely contemplation! Then i will cover the start of last route of Drug Elimination for our list and it is the Renal Excretion. Its the interplay and mathematics of three key processes namely Glomerular filtration, Tubular reabsorption and Tubular Secretion. For the bright today, I will be covering details, factors, mechanism, process, examples and all about Glomerular filtration and Tubular reabsorption. Rest of the episode's strings gonna reverb in next episode. Till then Chau..... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via https://linktr.ee/ispharmacologydifficult
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.I will be starting today's episode with a beautiful thought compilation about "Lantern" and the book "Sky Lantern" by Matt Makeloto, its a lovely contemplation!Then i will cover the start of last route of Drug Elimination for our list and it is the Renal Excretion. Its the interplay and mathematics of three key processes namely Glomerular filtration, Tubular reabsorption and Tubular Secretion.For the bright today, I will be covering details, factors, mechanism, process, examples and all about Glomerular filtration and Tubular reabsorption. Rest of the episode's strings gonna reverb in next episode. Till then Chau..... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult
Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.I will be starting today's episode with a beautiful thought compilation about "Lantern" and the book "Sky Lantern" by Matt Makeloto, its a lovely contemplation!Then i will cover the start of last route of Drug Elimination for our list and it is the Renal Excretion. Its the interplay and mathematics of three key processes namely Glomerular filtration, Tubular reabsorption and Tubular Secretion.For the bright today, I will be covering details, factors, mechanism, process, examples and all about Glomerular filtration and Tubular reabsorption. Rest of the episode's strings gonna reverb in next episode. Till then Chau..... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult
Chapter Three: How the proximal tubule is like Elizabeth Warren and other truths my friends from Boston taught me References for Chapter 3: Faisy C, Meziani F, PLanquette B et al. Effect of Acetazolamide vs. Placebo on Duration of Invasive Mechanical Ventilation among patients with chronic obstructive pulmonary disease: a randomized clinical trial. JAMA 2016 https://pubmed.ncbi.nlm.nih.gov/26836730/This randomized controlled double blinded multi-center study of acetazolamide to shorten the duration of mechanical ventilation (known as DIABLO) there was no statistically significant difference (though it may have been underpowered to do so).Salazar H, Swanson J, Mozo K, White AC, Cabda MM Acute Mountain sickness impact among travelers to Cusco, Peru J Travel Med 2012 https://pubmed.ncbi.nlm.nih.gov/22776382/ Investigators found that altitude sickness is common and alters travel plans for 1 in 5 travelers but was prescribed infrequently.Buzas GM and Supuran CT. Journal of enzyme inhibition and medicinal chemistry 2015 https://www.tandfonline.com/doi/full/10.3109/14756366.2015.1051042This review describes the use of acetazolamide to treat peptic ulcers and how it was later learned that H. pylori have carbonic anhydrase NORDIC idiopathic intracranial Hypertension Study Writing Committee. The effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA 2014 https://pubmed.ncbi.nlm.nih.gov/24756514/In this multi-centered trial, acetazolamide and low sodium weight reduction diet improved mild visual loss more than diet alone. Mullens W et al. Rationale and design of the ADVOR (acetazolamide in decompensated heart failure with volume overload trial) Eur J Heart Failure 2018 https://pubmed.ncbi.nlm.nih.gov/30238574/This reference explains the rationale for this ongoing trial.Gordon CE, Vantzelfde S and Francis JM. Acetazolamide in Lithium-induced nephrogenic diabetes insipidus NEJM 2016 https://www.nejm.org/doi/full/10.1056/NEJMc1609483A case report of efficacy of acetazolamide in a patient with severe polyuria.Zehnder D et al. Expression of 25-hydroxyvitamin D-1alpha hydroxylase in the human kidney. JASN 1999 This report explores the activity in the enzyme in nephron segments and suggests that the distal nephron may play an important part in the formation of 1,25 vitamin D https://jasn.asnjournals.org/content/10/12/2465Outline: Chapter 3 - This is chapter three, kind of the first real chapter of the book- Proximal Tubule- Reabsorbs 55-60% of the filtrate - Active sodium resorption - 65% of the sodium - 55% of the chloride - 90% of HCO3 - 100% glucose and amino acids - Passive water resorption - Water resorption is isosmotic - Secretion of - Hydrogen - Organic anions - Organic cations - Anatomy - S1, S2, S3 can be differentiated by peptidases - S1 more sodium resorption and hydrogen secretion, high capacity - S2 more organic ion secretion - Cell model - Basolateral membrane - Na-K-ATPase powers all the resorption - Luminal membrane - 100 liters a day crosses the proximal tubule cells - Microvilli to increase surface area - Microvilli has brush border which has carrier proteins as well as carbonic anhydrase - Water permeable, so sodium resorption leads to water resorption - Aquaporin-1 (sounds like this transporter is unique to the proximal tubule and RBC) - HCO3 is reabsorbed early, along with Na, resulting in increased chloride concentration which passively reabsorbed via paracellular route. - Tight junction has only one strand (on freeze fracture) as opposed to 8 in distal nephron - The Na-K-ATPase - Lower activity than in the LOH and distal nephron - Maintained intracellular Na at effective concentration of 30 mmol/L - Interior of the cell is negative due to 3 sodium out and 2 K in, then K leaks back out. - 3 Na out for 2 K in - An ATP sensitive K outflow channel on the basolateral membrane - Increased ATP slows potassium eflux - The idea is if Na-K slows, ATP will accumulate and this will slow K leaving, because there is less potassium entering. - K channel is ATP sensitive, ATP antagonizes K leak. - Highly favorable ELECTROCHEMICAL gradient for sodium to flow into the cell through the luminal membrane - Must be via a channel or carrier - Cotransporters - Amino acids - Phosphate - Glucose - Called secondary active transport - Countertransporters - Only example is H excretion - Basolateral membrane - Na-3HCO3 transporter - Powered by the negative charge in the cell- Chloride resorption - Formate chloride exchanger - Formate combines with hydrogen in the lumen, becomes neutral formic acid, and is reabsorbed where the higher pH causes it to dissociate and recycle again. - Dependent on continued H+ secretion - Chloride moves across basolateral membrane thanks to Cl and KCl transporters, taking advantage of negative intracellular charge- Passive mechanisms of proximal tubule transport - Accounts for one third of fluid resorption - Mechanism - Early proximal tubule resorts most of the bicarb and less of the chloride - Tubular fluid gets a high chloride concentration - Chloride flows through the tight junction down its concentration gradient - Sodium and water follow passively behind - Water moves osmotically into intercellular space from tubular fluid even though the osmolalities are equal since chloride is an ineffective osmole, so tonicity is not the same. ****** - Argues that bicarb is primarily important solute for passive resorbtion - Acetazolamide blocks Na and chloride resorption - Similar thing happens with metabolic acidosis where less bicarb is available to drive passive resorbtion of Na and Cl - Summary - Other than Na-K-ATPase Na-H antiporter main determinant of proximal Na and water resorption - 1. Direct bicarb resorption - Preferential bicarb resorbtion proximally drives passive chloride resorption - Drives active the formate exchanger for chloride resorption- Neurohormonal influence - AT2 drives a lot of Na resorption, primarily in S1 segment - Does not have a net effect on H-CO3 movement - Dopamine antagonizes sodium resorption - Blocks both Na-K-ATPase and - Na H antiporter- Capillary uptake - Starlings. Again - Low hydraulic pressure due to glomerular arteriole - High plasma on oncotic pressure from loss of the filtrate - The two together promote resorption - There maybe movement from interstitial back into tubular fluid (back diffusion) conflicting data- Glomerular tubular balance - The fractional tubular reabsorption remains constant despite changes in GFR (tubular load) - It is essential the GFR is matched by resorption - The rise in capillary osmotic pressure with increased GFR via increased filtration fraction is one mechanism of GT balance - Glomerular tubular balance os one of three mechanisms that prevents fluid delivery from exceeding the resorptive capacity of the tubules - GT balance - TG feedback - Autoregulation - GT balance can be altered if patients are volume overloaded or depleted - Closes this section with a story of a kid born without a brush border - Primacy of sodium in proximal tubule activity - Discusses bicarb resorbtion - There is no Tm for Bicarb as long as volume overload is prevented, in rats can rise over 60! - If you give NaHCO3 you get volume overload and the Tm I about 60 - Glucose - S1 and S2 have high capacity, low affinity glucose resorption - S3 has high affinity 2 Na fo every glucose - Tm glucose is 375 mg/min - For a GFR of 125t that comes out to 300mg/dL - 125 ml/min * 3mg/ml (300 mg/dL) = 375 mg/min - Functionally this is 200 mg/dL due to splay - Urea - Only 50-60 of filtered urea is excreted - Calcium Loop and distal tubule - Phosphate - 3Na-Phosphate high affinity transporters late in proximal tubule - three types of Na-Phos transporters, type 2 are the most important - regulated by PTH and plasma phosphate - PTH suppresses Phos resorption -Metabolic acidosis also reduces phosphate resorption (good to have phosphate in the tubule to soak up H+ - Decreased tubular pH converts HPO42- to H2PO4- which has lower affinity for phosphate binding site - Mg Loop and distal tubule - Uric AcidWhy do I love acetazolamide?- I love the proximal tubule- Many uses- Often forgottenMOA- Inhibit carbonic anhydraseMain effects- Renal: less bicarb reabsorption (ie less H secretion) à more distal Na/bicarb delivery à hypokalemic metabolic acidosis- Brain: reduce CSF production, reduce ICP/IOP, aqueous humor- Pulm: COPDNotes- Tolerance develops in 2-3 days- Sulfonamide derivative- Highly protein bound, eliminated by kidneys Source: Buzas and upuran, JEIMC, 2016S Data:1968 - High altitudeHigh altitude usually results in respiratory alkalosisAcetazolamide – lessens symptoms of altitude sickness (insomnia, headache) which occur because of periodic breathing/apnea1979- NEJM study took 9 mountaineers asleep at 5360 meters à improvement in sleep, improved SaO2 from 72 to 78.7 mmHg, reduce periodic breathing, increased alveolar ventilation (pCO2 change from 37 mmHg to 30.8mm Hg)1950s - Seizures/migrainesCAI reduces pH (more H intracellularly), K movement extracellularly à hyperpolarization and increase in seizure thresholdWeak CAI (Topamax, zonisamide) but not though to be important mechanism of antiseizure effect (topamax enhances inhibitory effect of GABA, block voltage dependent Na and Ca channels)Pulmonary/COPDThought to help with the metabolic alkalosis and as a respiratory stimulant to increase RR, TV, reduce ventilator timeIn 2001 Cochrane review – no difference in clinical outcomes, but did reduce pH and bicarb minimallyDIABLO study (RCT) on ventilated COPD patients – no difference in median duration of mechanical ventilation despite correction of metabolic alkalosisHigh altitude erythropoiesis (Monge disease)First described in 1925 via Dr. Carlos Monge Medrano (Peruvian doctor), seen in people living > 2500-3000 meters (more common in South America than other high altitude areas)Usually chronic altitude sickness with HgB > 21 g/dL + chronic hypoxemia, pHTNAcetazolamide – reduces polycythemia because induces a met acidosis à increases ventilation and arterial PPO2 and SaO2 à blunts erythropoiesis and reduces HCT and improves pulmonary vascular resistanceGI ulcersWhen H2 and PPI available, less useHistory: 1932 – observed alkaline tide, presumed existence of gastric CA (demonstrated in 1939)Acetazolamide was used to inhibit acid secretion in 1960s, ulcer symptoms, with reversible metabolic acidosis, BUT lots of SE (electrolyte losses, used Na/K/Mg salts to help, renal colic, headache, fatigue, etc)Later found H. Pylori encodes for two different CasHelps to acclimatize to acidic environmentBasically, the Ca changes CO2 into H+ and HCO3They also have a urease which produces NH3The NH3 binds with H+, leaving an alkaline environment for them to live inInhibition of CA with acetazolamide is lethal for pathogen in vitro1940sFound there was CA in pancreasThought acetazolamide to reduce volume of secretions from NGT (output from exocrine pancreas) Source: Human Anatomy at Colby Blog Diuretic resistanceIf develop hyperchloremic metabolic alkalosis, short course of acetazolamide + spironolactone (b/c need distal Na blockage) à can helpMay help with urine alkalization (ie uric acid stone) but increases risk of calcium phosphate stonesADVOR trial acetazolamide in HF exacerbation in Belgiumuse may help to prevent new episode, lower total diuretic doseCSF reduction (pseudotumor cerebri)Reduces CSF by as much as 48% when > 99.5% of CA in choroid plexus is inhibitedNORDIC trial (acetazolamide v. placebo) – improvement in visual symptoms especially if advanced papilledema, and reduced opening pressure)Side note also used off label to help with increased ICP and CSF leaks, as alternative to VP shunts, repeat LPs, etc Source: Eftekari et al, Fluid Barriers CNS, 2019.
The exciting conclusion to Chapter Two: Renal Circulation and Glomerular Filtration Rate - Determinants of GFR - First step in making urine is separation of an ultrafiltrate - Governed by starling forces - Balance of hydraulic and osmotic forces - GFR = LpS (P gc – P us - Osmotic Pressure Cap p) - Normal GFR 95 in women, 120 in men - Cap Hydrolic pressure remains constant - glom cap Oncotic progressively rises - Due to filtration of protein free fluid (protein concentration rises in the capillary) - Filtration gradient begins at 13 mmHg and falls to zero after filtration of 20% or RPF! - GFR is capped at 20% of RPF called filtration equilibrium - So GFR is dependent on RPF, unless you can change glomerular hydraulic pressure - Glomerular hydraulic pressure is controlled by balance of twin arteriole (afferent and efferent) - Constriction of afferent arteriole reduces RPF, GFR, and glom pressure - Dilation of afferent arteriole increases RPF, GFR, and glom pressure - Constriction of the efferent arteriole increases Glom pressure, increasing GFR - Besides glom hydrostatic pressure the other starlings forces are rarely relevant to changes in GFRLetty says: referred to this NEJM review article later JC thought she was referring to something else -see #2- and then Roger referred to this again)Normotensive Acute Renal Failure from Gary Abuelo in NEJM 2007. https://www.nejm.org/doi/10.1056/NEJMra064398 (note in this article, Dr. Abuelo acknowledges the newer terminology of the time, AKI rather than ARF but chooses not to embrace it). In figure 2, he highlights the classic examples of how autoregulation can be affected. In the table, additional examples are provided but all within the framework of alterations related to autoregulation and the interplay between the two resistance vessels.- Regulation of GFR - Autoregulation - The ability to keep glomerular pressure constant over wide range of systemic arterial pressure - When pressure < 70 autoregulation fails and GFR will fall with decreases in systemic pressure - When pressure falls below 40-50 GFR ceases - At least some of this autoregulation is mediated with Ang2. Giving ACEi markedly disrupts autoregulation - Nitric oxide, not important - TGF - Chloride in macula densa - Blocked by furosemide - Group affect of nephrons - Ang 2 sensitizes - Adenosine mediates - Function of TGF - 90% of filtrate is reabsobed in PT and LOH - 10% is reabsobed dismally - Need to control the amount of fluid delivered distally to prevent overwhelming the resorptive capacity of the distal nephron - Talks about acute renal success without naming it (but did reference it) - Mentions glucosuria blunts TGF. Hmmm... - Neurohormonal influences - Volume changes in ang2, sympathetic NS - Role of PGE - Interesting discussion of change of the nephrons perfumed with volume depletion, shifting of blood from outer coretex to inner medullary cortical gloms with their long loops - Dopamine and ANP both increased with volume up - Dopamine causes vasodilation of afferent and efferent arteriole - ANP causes afferent vasodilation and efferent vasodilation constriction, increasing GFR without affecting RPF - Glomerular hemodynamics and renal failure - Decreased glomerular mass results in hyperfiltration of remaining gloms - Mediated through afferent vasodilationJC talks about this classic study in critical care: High vs. Low blood pressure target in Septic Shock. https://www.nejm.org/doi/pdf/10.1056/NEJMoa1312173In this multi-center open label trial of 776 patients randomized to either a MAP of 65-70 or 80-85 with the primary endpoint of mortality. There was no difference in mortality at 28 days between the two groups (but a small difference in AKI in the patients who had chronic HTN- in the higher BP target, there was a decrease in need for RRT; there was also a higher incidence of afib in the high target group overall). - Results in compensation and stable GFR in short term, long term maladaptive - Reason for ACEi- Clinical Evaluation of Renal Circulation - Concept of clearance and measurement of GFR - GFR as an index of functioning renal mass - Had a patient today s/p nephrotomy, 72 years old, Cr0.9!Melanie referred to this article in Circulation which demonstrates that SGLT2 inhibitors do decrease single nephron GFR (in mice) and that this is related to a decrease in the afferent arteriole diameter and then they show that this is related to a local increase in adenosine. Kidokoro K, Cherney DZI et al. Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging Circulation 140 (4) 2019https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037418 - Fall in GFR earlier and only sign of renal disease - Serial monitoring is used to assess severity and follow the course of disease - GFR is useful for dosing drugs - How to measure GFR - Consider fructose polysaccharide inulin (love the parenthetical, not insulin) - Inulin filtered = inulin excreted - Filtered inulin = plasma inulin concentration x GFR - Inulin excreted = urine concentration x urine volume - Use Alber a to get GFR = [Urine]insulin x urine volume / [plasma]inulin - GFR = inulin clearance - There is not an available assay for inulin - Creatinine clearance - Freely filtered - Not reanbsorbed - Not metabolized - Small amount excreted - CrCl exceeds GFR by 10-20%Roger says the SGLT2 inhibitor story is about the afferent arteriole and he thought it reminded him of the MDRD study and the concept that the lower protein intake would be protective and delay the progression of CKD. The concept was that low protein diets would decrease glomerular pressure by decreasing the intake of amino acids that lead to arteriolar vasodilation and increased GFR. Klaur S, Levey AS et al. The effects of Dietary Protein Restirciton and blood-pressure control on the progression of chronic renal disease. NEJM 1994 330:877-884. https://www.nejm.org/doi/full/10.1056/nejm199403313301301 - Compensated for by noncreatinine chromogens (acetone proteins, as Orbi acid, pyruvate) that over estimate Cr by 10-20% - Cr Cl = [Urine]cr x urine volume / [Plasma]cr - Two major limitations - Incomplete collections - 20-25 mg/kg in adult men - 15-20 mg/kg in adult womenThe term “Acute renal success” comes from Thurau K and Boylan JW. Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 1976 61(3): 3038-15. - Falls by 50% from age 50 to 90 to 10 mg/kg - Increased tubular secretion with decreased kidney function - GFR of 40-80 cr secretion may account for as much as 35% of creatinine excretion - In some cases CrCl can exceed GFR by a factor of 2 - Give cimetidine 1200 mg! - It is important to appreciate however that exact knowledge of GFR is not required. More important to know if GFR is changing - Why is radio labeling the solution DTPA and iothalamate? - Talks about the reality of progressive disease despite stable GFR and CrCl - On to plasma Cr and GFRIf you think placing dialysis lines is too easy, here is a wonderful review of micropuncture technique in the kidneys by Volker Vallon.Micropuncturing the Nephron. Pflugers Arch 2009 458(1): 189-201. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954491/ - Creatinine excretion = creatinine production (and this is constant) - Creatinine excretion = [Cr] x GFR = constant - If GFR falls in half, creatinine excretion will fall in half, while creatinine production remains the same, so creatinine will rise and rise until [Cr] x GFR = creatinine production and then it will level off. - Changes in creatinine load - High protein diet can increase it - Vegetarian diet can decrease itJC brought up studies on fenoldopam, of which there are many. This is one such study in patients undergoing cardiac surgery. JAMA 2014 Bove T et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial https://pubmed.ncbi.nlm.nih.gov/25265449/ - Cooked meat can increase Cr by 1 mg/dL - Talks about need for steady state to assess GFR - Talks about the curvilinear relationship - Then he talks Cockcroft GaultThe one, the only: The Cockcroft Gault: Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41, 1976 https://pubmed.ncbi.nlm.nih.gov/1244564/ - Cirrhosis masks kidney insufficiency, low meat intake, low BUN production - Can someone explain what we are supposed to take from figure 2-12 - Stable Cr does not mean stable kidney diseaseRoger describes the study design for the seminal paper on the use of ACE inhibitors to slow the decline in renal function in diabetic kidney disease (then called diabetic nephropathy) and the decision to use the doubling of the serum creatinine as an endpoint. Lewis EJ The effect of Angiotensin-converting-enzyme inhibition on diabetic nephropathy NEJM 1993 https://www.nejm.org/doi/full/10.1056/NEJM199311113292004 - Ketoacidosis can raise the Cr 0.5 to 2.0mg/dL - On to BUN - Destination of amino acids produces ammonia - We detoxify ammonia by converting to urea - Increased with increased protein load - Increased catabolismMelanie mentioned an old study on ingestion of expired blood: Cohen TD. Induced azotemia in humans following massive protein and blood ingestion and the mechanism of azotemia in gastrointestinal hemorrhage. AM J Med Sci 1956 https://pubmed.ncbi.nlm.nih.gov/13302213/ - Tetracycline causes decreased anabolism - Trauma - Steroids - Urea excretion is variable and tied to hydration and FF - Renal plasma flow and PAH
Back by popular demand…all two of you…the second chapter of The Clinical Physiology of Acid Base and Electrolyte Disorders. Chapter Outline- Renal Circulation and GFR - RBF is 20% of cardiac output - In terms of mL per 100 g organ weight it is 4x the liver and exercising muscle and 8x coronary blood flow! - After the glomeruli the efferent arteriole have two fates - Peritubular capillaries in the cortex - Peritubular capillaries are not necessarily associated with their parent glomeruli. Weird. - Vasa recta from juxtamedullary glomeruli in the medullaJoel Says: This seems wrong. Solute balance can be maintained down to a very low GFR. The R^2 here would be very low. Prove me wrong. - States that GFR is an important determinant of solute and water excretion. - Glomerular anatomy and function - Structure Four editions of the Bud Bible up top and a copy of Bud Light on the bottom. - Glomerulus is a tuft of capillaries - Enclosed in a capsule of epithelial cells, called Bowman's capsule - The epithelial cells of Bowman's capsule are continuous with the epithelial cells of the proximal tubule Looking at scanning EMs of the glomerulus is one of life's simple pleasures—Josh. Josh says: Look at the review in Nature Reviews Nephrology from Rachel Lennon's groupComplexities of the glomerular basement membrane - Filtration barrier - Epithelial cell (podocyte) - Epithelial cells adhere to the basement membrane via foot processes and the foot processes have slit diaphragms - Basement membrane New Super-resolution structure of the GBM: https://elifesciences.org/articles/01149 Hi res microscopy is really hi-res. Technique is call ed STORM. Melanie talks about conduits through the glomeruli. Here is a cool review: Why until just now? Undiscovered uniqueness of the human glomerulus! by L. Gabriel Navar, Owen RichfieldAm J Physiol Renal Physiol. 2018 Nov 1; 315(5): F1345–F1346. Published online 2018 Aug 15. doi: 10.1152/ajprenal.00369.2018 PMCID: PMC6293291 - Produced by both the endothelial cells and podocytes - Formed from type IV collagen - Abnormalities of type 4 collagen cause Alport - The gene coding for the alpha 5 chain is the culprit - COL4A5 - Abnormal Alpha 3 and 4 chains can also cause hereditary nephritis - Has other substances - Laminin - Nidogen - Heparin sulfate proteoglycans - Provides the negative charge - Enthothelial cell (fenestrated) - Protein excretion - Glomerular function: allow filtration of small solutes (Na and urea) while preventing filtration of larger molecules - Insulin MW 5,200 is freely filtered (upper range of freely filtered) - Preventing loss of protein prevents - Negative nitrogen balance - Development of hypoalbuminemia - Infection from loss of immunoglobulin - Size and charge selectivity of the GBM - pores are between cords of type 4 collagen - The epithelial cells and slit diaphragms matter - Macromolecules that pass through GBM can accumulate underneath the epithelial layer - Isolated GBM in invitro studies is much more permeable to than intact glomerulus - There is increased protein filtration in areas where the epithelial cells have detached from the GBM Josh really likes this figure from another Nature Reviews Nephrology paper. This one by Moeller and Chia-Gil. - Mutations in nephrin, localized to the slit diaphragm causes congenital nephrotic syndrome - Charge selectivity is important - Neutral and cationic particle are more likely to be filtered - Albumin (negative charge) is filtered 5% as well as same size neutral dextrans - In glomerular disease, while there is increased filtration of proteins there is decreased filtration of small solutes due to loss of glomerular surface areaJC says: Take a look at this research on the serving coefficient in glomerular disease. Some surprising results.Glomerular dysfunction in nephrotic humans with minimal changes or focal glomerulosclerosis - Why do people in remission have what appears to be spilling more high molecular radius particles than normal and why do patients with active MCD have lower clearance across all molecular diameters? - Other glomerular functionsJosh says: Take a look at this interesting paper by Butt et alA molecular mechanism explaining albuminuria in kidney disease - Synthetic - Epithelial cells produce GBM - Phagocytic - Remove circulating macromolecules that pass through GBM and get trapped in subepithelial spaceJosh says: The sFLT1 (soluble VEGF receptor) relationship to preeclampsia is just so cool. And here's the paper:Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsiaAnd in the NEJM: VEGF Inhibition and Renal Thrombotic Microangiopathy - Endocrine - Enthothelial cells regulate vascular tone by releasing - Prostacyclin - Endothelin - Nitric oxideJC says: Do yourself a favor and spend some time learning about extraglomerular mesangial cells with Stuart Shankland Extraglomerular origin of the mesangial cell after injury. A new role of the juxtaglomerular apparatusJoel adds, if you ever get a chance to party with Dr. Shankland, don't skip out. - Mesangial cells, two types - Intrinsic Mesangial cell - Microfilaments similar to smooth muscle - Responds to Ang2 - Regulates glomerular hemodynamics - Can release cytokines - Can respond to cytokines by proliferation - Circulating macrophages and monocytes - Phagocytic function - Clear molecules that get through the endothelial wall but cant get through the GBMJosh says, “Topf, get it right. Its Ree-nin not renin. Classic letter to JAMA. - Renin-Angiotensin System - Afferent arteriole contain specialized cells called juxtaglomerular cells - Produce prorenin which cleaved into renin - Stimuli for renin release - Hypotension - Volume depletion - Increased sympathetic activity - Renin catalyze the production of ang1 from angiotensinogen - Ang1 is catalyze to Ang2 by ACE located in the - Lung - Endothelial cells - Glomeruli itself pic.twitter.com/DaDfS7u8se— Roger Rodby (@NephRodby) February 22, 2021 - Discussion of local renin and Aniotensinogen - Explains why ACEi are useful even with low systemic renin levels and Ang2 - Actions of Ang2 - Sodium and water retention - By direct Na reabsorption in the early PT (and in the proximal tubule, water is permeable to the epithelium so every sodium reabsobed, brings a water molecule along for the osmotic ride. - Stimulates the Na-H antiporter - 40-50% of Na reabsorption in the S1 segment of the PT is due to Ang2 - By stimulation of aldosterone - Ang2 that stimulates Aldo comes from the kidney and from the adrenal gland itself - VasoconstrictionJosh talks angiotensin:Tenses the angios--love this Melanie!1961 paper from del Greco (who's endowed chair Dan Batlle has now) trying AT2 in "hopeless" patients and dialysis patients:https://jamanetwork.com/journals/jama/article-abstract/332265Great EM-crit/pulmcrit discussion here:https://emcrit.org/emcrit/deeper-vasopressors-athos-3/and caveats here:https://emcrit.org/pulmcrit/angiotensin-ii/ - Arteriolar vasoconstriction - Ang2 important for raising BP in RAS - Ang2 important in maintaining BP with volume depletion or in CHF, liver disease - Giving ACEi to cirrhosis can cause BP to dump 25 points - Regulation of GFR - Affects constriction at afferent arteriole and efferent arteriole - Mediated via thromboxane JC talks about the ATHOS trial and how there is a signal for improved outcomes especially in patients requiring renal replacement therapy.Angiotensin II for the Treatment of Vasodilatory ShockOutcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II - Afferent arteriole starts bigger so reductions have less of an effect than constriction does on the narrower efferent arteriole. - This results in a fall of RBF due to increased resistance but maintaining GFR by increasing inrtaglomerular pressure. - Also stimulates prostaglandins which are vasodilator, modulating this affectJoel says: You haven't heard of the Trolly Problem? Oh you need to take 5 minutes and read this. - It can stimulate contraction of the mesangium reducing surface area of the glom reducing filtration. - It sensitizes the afferent arteriole to TG feedback so it can reduce glomerular flow in response to increased chloride detection in the TLoH. - Control of renin secretionEver wanted to know about intrarenal renin concentrations? Yeah, me neither. But JC's got you covered: Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. - Primarily sodium intake, increased intake results in less renin - Mediated by baroreceptors - Baroreceptors in afferent vessel wall - Cardiac and arterial baroreceptors which activate the sympathetic nervous system and catecholamines which then stimulates reninRoger says: Do your self a favor and read about Yanomamo IndiansBlood pressure and electrolyte excretion in the Yanomamo Indians, an isolated population - Cells of the macula densa in the early distal tubule which detect decreased chloride delivery - This allows loop diuretics to be particularly effective at increasing renin as they block chloride resorption - Suppression of renin in response to chloride is mediated by adenosine - Stimulation of renin in response to decreased chloride is mediated by PGE - The PGE cause local vasodilation so the kidney maintained a rich blood flow while using renin and Ang2 to cause systemic vasoconstrictionAnna's notes for the deep dive in glomerular barrierOur understanding is based on technology available at the time. Even in 1920s, there was thought that tubular reuptake of protein may be important, but studies never demonstrated this til 2007 and even then are debated. 2007 Russo, et al (and BM at IU!) showed that The normal kidney filters nephrotic levels of albumin and that failure of retrieval by proximal tubule cells is what separates proteinuria from nonproteinuria. This was countered by a study in 2009 demonstrating much lower GSC and suggesting that the high GSC in the 2007 could be the result of nonphysiologic states.Check out this 2008 debate in JASN regarding the validity of the charge model and “normal” albumin in the glomerular filtrate. Hotly debated with too many studies to cite. 2017: Lawrence et al publish their findings that the GBM and podocyte processes are sufficient and the slit diaphragm likely does not exist. They used labeled proteins and confocal microscopy to determine migration of particles through the enodthelium and GBM. They also injected NaSCN oligoclusters from the size of albumin (66kDa)up to the size of IgG dimers (300 kDa) into mice, then fixed. The size-sensitive permeation into the lamina densa of the GBM and the podocyte glycocalyx of albumin and uptake of any “escaping” albumin by the proximal tubule was also observed. This countered the common prior conception that the slit diaphragms pores are the site of albumin “capture.” For your reading pleasure the review of Clinical Physiology of Acid-Base and Electrolyte Disorders Fourth Edition in Annals of Internal Medicine
Better Edge : A Northwestern Medicine podcast for physicians
In this episode of the Better Edge Podcast, Aneesha Shetty, MD, MPH, assistant professor of Medicine in the Division of Nephrology and Hypertension, discusses finding from a recent case report published in the Journal of the American Society of Nephrology.This study highlights an emerging COVID-19 related kidney disease that is characterized by podocytopathy and/or collapsing FSGS. In investigating this phenomenon among six patients with proteinuria collapsing FSGS and COVID-19 infection, it was observed that the patients were all of recent African ancestry. This led to further investigation into whether this kidney disease is associated with the high risk APOL1 genotype. This association may help predict how a patient will do with COVID-19, their needs after infection recovers, and sheds light on APOL1 genotypes and kidney disease.
Dear Listeners, An estimated 10% of school-aged children will have proteinuria. About 0.1% of them will have persistent hematuria requiring further investigation. Transient proteinuria can be caused by stress, exercise, cold exposure, dehydration, and orthostasis. Persistent proteinuria can be caused by Glomerular or Tubular Disease. Glomerular disease is most common with differential including infections (Strep […] The post Podcast 70: Proteinuria in Children appeared first on Primary Medicine Podcast.
Asymptotic, nephrotic syndrome, nephrotic syndrome, RPGN
Dr. Centor discusses the rationale for and against incorporating race into equations used to estimate glomerular filtration rate with Dr. Ashwini R. Sehgal.
Having trouble knowing what to do with those hard to classify patterns of glomerular disease? Worry not. Dr. Silva is here to help!
Having trouble knowing what to do with those hard to classify patterns of glomerular disease? Worry not. Dr. Silva is here to help!
Clinical Journal of the American Society of Nephrology (CJASN)
This is a podcast summary by Julien Hogan on behalf of his coauthors for the article entitled "Sex and Glomerular filtration Rate Trajectories in children: Insights from the CKiD Cohort Study".
Clinical Journal of the American Society of Nephrology (CJASN)
This is a podcast summary by Julien Hogan on behalf of his coauthors for the article entitled "Sex and Glomerular filtration Rate Trajectories in children: Insights from the CKiD Cohort Study".
Glomerular filtration rate by Intrinsic and extrinsic mechanisms. Intrinsic mechanisms( auto regulation that involves myogenic and tubuloglomerular regulations) and extrinsic mechanisms that involve activation of the sympathetic nervous system and RAAS system through the activity of Macula Densa. --- Support this podcast: https://anchor.fm/kamesa-anota/support
Glomerular disease is generally thought of as nephritic vs. nephrotic. In this episode, we will try to understand the difference between the two, acknowledging that these can occur on a spectrum. We’ll talk about specific diseases that fall under each category and work through several case vignettes, highlighting key features that you should know for each. It’s tough to get a hang of these diseases, but this episode is definitely a step in the right direction!
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Jun Shoji, MD, Assistant Professor of Medicine, Connie Frank Transplant Center, UCSF. Series: "UCSF Transplant Update" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 35053]
Glomerular filtration rate, or GFR, is generally accepted as the best overall index of kidney function, and a decrease in GFR has important implications for prognosis in patient management. GFR is most commonly estimated by calculation, using the serum concentration of an endogenous filtration marker such as creatinine and demographic variables such as age, sex, and race. In the March 2019 issue of Clinical Chemistry, a paper investigated the possibility of developing a more accurate estimate of GFR, using a panel of metabolites measured by quantitative liquid chromatography, tandem mass spectrometry without creatinine, cystatin C, or demographic variables.
In the March 2019 issue of Clinical Chemistry, Professor Andrew Levey and others from a multinational consortium of institutions, published a study titled, “Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS-MS.” In fact, we have another podcast from one of the authors of that paper available. But today, we’re joined by Dr. Anders Berg, the Associate Medical Director of the Core Laboratories at Cedars-Sinai in Los Angeles, who co-authored an editorial that accompanied the paper. Dr. Berg is here to help us deconvolute the significance of this intriguing study and where this research might lead us in the future.
Part 1 of the summary of Consensus Recommendations for Standard Therapy of Glomerular Disease in Dogs
Dr. Andrew Bomback is an Assistant Professor of Medicine at Columbia University and a specialist in glomerular diseases. He is also a writer, having published in the Los Angeles Review of Books, The Atlantic, and The Kenyon Review, among others. His recently published book is entitled Doctor. It’s part of a series called Object Lessons - short books that are part memoir, part nonfiction, each looking at the ‘hidden lives’ of an everyday object or concept. We talk about that book as well as his thoughts on working as both a physician and a writer.Doctor (Object Lessons) by Andrew Bomback https://www.bloomsbury.com/us/doctor-9781501338175/https://www.amazon.com/Doctor-Object-Lessons-Andrew-Bomback/dp/150133817X Music by Scott Holmes “Follow Your Dreams” licensed under CC BY-NC 4.0
On this episode of Throwback Thursday, Dr. Silva discusses the early classifications of kidney disease and the origins of our current nomenclature.
--- Support this podcast: https://anchor.fm/brad-richardson/support
March is National Kidney Month. According to the National Institute for Diabetes and Digestive and Kidney Disease 30 million people in the United States are living with a diagnosis of chronic kidney disease. 660,000 American have renal failure with 470,000 patients on dialysis. 190,000 people live with a kidney transplant. Each year chronic kidney disease kills up to 50,000 Americans, more than either breast or prostate cancer. High blood pressure and diabetes are the two leading causes of chronic kidney disease. kidney disease in its early stages is silent and has no symptoms. For this episode, I am going to the very periphery of the field of Urology, a surgical specialty, and into the field of Nephrology, to talk a little bit about how your kidneys work, so you can understand if you are at risk or have evidence of chronic kidney disease. Your Glomerular Filtration Rate (GFR) represents the total filtering capacity of millions of tiny filters, each one called a glomerulus. March is National Kidney Month. Protect your glomeruli. Control your blood pressure. Watch your diabetes. Stop smoking. Stay hydrated.
By: Jim Harms Recorded at Princeton Baptist Hospital on 8/10/17.
Our kidneys need to filter 120mL per minute (or 180L per day) of blood in order to maintain the appropriate amount of salts, pH, waste, and other components in the blood. The glomerulus is the filter that decides what can and cannot get filtered. If this membrane is damaged or disrupted, patient health can rapidly decline. What is the glomerulus? How does it work? How can it be damaged? What are some diseases of the glomerulus?
The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C–based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL · min−1 · (1.73 m2)−1. Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C–based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations.
Commentary by Dr. Valentin Fuster
Estimating Glomerular Filtration Rate or GFR is important for the detection and monitoring of impairment of renal function for safety in the use of potentially nephrotoxic pharmaceuticals and radiographic contrast media, and for administration of correct dosage of drugs cleared by the kidneys. Even though it is not ideal, serum creatinine is widely used as a marker for calculating Glomerular Filtration Rates.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 16/19
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.
Purpose of review We have summarized recently published glomerular parietal epithelial cell (PEC) research, focusing on their roles in glomerular development and physiology, and in certain glomerular diseases. The rationale is that PECs have been largely ignored until the recent availability of cell lineage tracing studies, human and murine PEC culture systems, and potential therapeutic interventions of PECs. Recent findings Several new paradigms involving PECs have emerged demonstrating their significant contribution to glomerular physiology and numerous glomerular diseases. A subset of PECs serving as podocyte progenitors have been identified in normal human glomeruli. They provide a source for podocytes in adolescent mice, and their numbers increase in states of podocyte depletion. PEC progenitor number is increased by retinoids and angiotensin-converting enzyme inhibition. However, dysregulated growth of PEC progenitors leads to pseudo-crescent and crescent formation. In focal segmental glomerulosclerosis, considered a podocyte disease, activated PECs increase extracellular matrix production, which leads to synechial attachment and, when they move to the glomerular tuft, to segmental glomerulosclerosis. Finally, PECs might be adversely affected in proteinuric states by undergoing apoptosis. Summary PECs play a critical role in glomerular repair through their progenitor function, but under certain circumstances paradoxically contribute to deterioration by augmenting scarring and crescent formation.
Glomerular Filtration
Click here for audio of lecture.
Click here for audio of lecture.
Click here for audio of lecture.
Glomerular Filtration
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Mon, 10 May 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11512/ https://edoc.ub.uni-muenchen.de/11512/1/Kumar_Dilip.pdf Kumar, Dilip
Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07
Fri, 8 Feb 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9057/ https://edoc.ub.uni-muenchen.de/9057/1/Blutke_Andreas_Falko.pdf Blutke, Andreas Falko ddc:500,
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 05/19
This study aimed to evaluate whether a late blockade of the chemokine receptor 1 (CCR1) (i.e. blockade began after establishment of a progressive renal disease) with its low molecular weight antagonist BX471, could alleviate renal damage in MRL lpr mice, through reducing leukocyte recruitment to the kidney. Immunhistological evaluation and cell transfer studies showed that BX471 could reduce the number of infiltrating leukocytes into the renal interstitium. This was followed by a reduction of interstitial fibrosis and improvement of renal function. Glomerular disease was histologically (leukocyte infiltration and immune complex deposition) and clinicaly (proteinuria) unchanged after BX471 treatment. There was also no Th1 or Th2 shift. Consequently, CCR1 blockade, began in the progressive phase of the lupusnephritis of MRL lpr mice, improves renal function through selectively alleviating interstitial inflammation. CCR1 antagonists could therefore offer new therapeutic alternatives for advanced immunecomplex glomerulonephritis but also for other progressive renal diseases.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 04/19
By means of their proliferative and secretory potential glomerular mesangial cells are thought to be important mediators of glomerular inflammation and fibrosis. Recent studies have established a direct role for NO in the regulation of gene expression in different cell types including mesangial cells. Representational difference analysis was used to investigate changes in gene expression elicited by the treatment of S-Nitroso-L-glutathione in rat mesangial cells. We identified 7 upregulated and 11 downregulated genes. Four out of 11 downregulated genes, connective tissue growth factor, thrombospondin-1, collagen type I alpha 1 and collagen type I alpha 2, are matricellular genes linked to inflammation and fibrosis of different organs including the kidney. Results were verified by using Northern blot analysis, quantitative real time PCR and protein analysis methods in human mesangial cells treated with a series of NO donors. We validated our findings by inducing endogenous NO production by cytokine stimulation. Real time PCR analysis showed that two additional matrix related genes, biglycan and collagen type IV alpha 2 are also downregulated by NO. Connective tissue growth factor promoter studies in mesangial cells demonstrated that NO acts at the transcriptional level to suppress gene expression. These results reveal a complex role of NO in regulating gene expression in mesangial cells and suggest an antifibrotic potential for NO.
The involvement of the kidney in the pathogenesis of hypertension has long been recognised, although the specific renal mechanisms underlying this phenomenon are still unknown. A current hypothesis attributes hyper tension to a reduction in glomerular filtration area by glomerular loss, The present study analyses the relationship between glomerular number and volume and conscious systolic blood pressure (SBP) in 4- to 53-week-old hypertensive (PHR) and normotensive (PNR) rats of the Prague strain. Adult PHRs had higher SEP, were larger and had larger kidneys than PNRs, but 20% fewer glomeruli, A significant negative correlation between SEP and glomerular number was found in PHR males, but not in PHR females or PNRs. There was no correlation at all between glomerular volume and SEP and, in young animals, both SEP and glomerular number were higher in PHRs than in PNRs. In addition, in adult PHRs, glomerular volume and SEP were higher in males than in females. In summary, a generally valid, causal relation-ship linking raised blood pressure to decreased glomerular number or volume could not be demonstrated in the Prague rat model of genetically determined hypertension. The nature of the renal mechanism(s) determining the hypertension in this model remains unknown. Copyright (C) 2000 S. Karger AG, Basel.
Binding sites for atrial natriuretic factor (ANF) were determined on isolated rat glomeruli as well as on glomerular membranes. To define optimal conditions, binding of ANF was investigated varying incubation time, temperature and protein concentration. Binding conditions were found to be best at 4°C for 5 hours with 15 μg of glomerular protein. Saturation and affinity cross-linking experiments confirmed the presence of two distinct receptor subtypes - the B-receptor (130 kDa) and the C-receptor (65 kDa). Quantitative differentiation of both ANF binding sites was achieved by competitive displacement with two different unlabeled ANF ligands: a) rANF(99-126) (homologous displacement), b) des(18-22)rANF(4-23)NH2(heterologous displacement). Intact glomeruli and glomerular membranes did not differ significantly in receptor density for the B-receptor (71 ± 37 vs. 94 ± 53 fmol/mg protein) or the C-receptor (976 ± 282 vs. 966 ± 167 fmol/mg protein) or in affinity constants for the B-receptor (43 ± 36 vs. 52 ± 44 pM) or the C-receptor (876 ± 377 vs. 307 ± 36 pM). Glomerular membranes compared to glomeruli showed less nonspecific binding and less intra-assay variation of measuring points done in triplicates. This method of selective displacement should allow to study the influence of various physiological and pathophysiological conditions on the binding properties of B-and C-receptors for ANF.
The renal response to atrial natriuretic factor is blunted in cirrhosis with ascites. This might be due to alterations of renal receptors for atrial natriuretic factor. Therefore density and affinity of glomerular atrial natriuretic factor binding sites of bile duct-ligated rats with ascites (n = 10) and of sham-operated controls (n = 10) were determined. Glomerular atrial natriuretic factor binding sites were identified to be of the B-(biologically active) and C-(clearance) receptor type. Discrimination and quantitative determination of B and C receptors for atrial natriuretic factor were achieved by displacement experiments with atrial natriuretic factor(99-126) or des(18-22)atrial natriuretic factor(4-23), an analogue binding to C receptors only. Density of total glomerular atrial natriuretic factor binding sites was significantly increased in bile duct-ligated rats (3,518 ± 864 vs. 1,648 ± 358 fmol/mg protein; p < 0.05). This was due to a significant increase of C-receptor density (3,460 ± 866 vs. 1,486 ± 363 fmol/mg protein; p < 0.05), whereas density of B receptors was not significantly different in bile duct-ligated rats (58 ± 11 vs. 162 ± 63 fmol/mg protein). Affinity of atrial natriuretic factor to its glomerular binding sites did not differ significantly between both groups. These data suggest that an altered glomerular atrial natriuretic factor receptor density could be involved in the renal resistance to atrial natriuretic factor in cirrhosis with ascites.
Mon, 1 Jan 1990 12:00:00 +0100 https://epub.ub.uni-muenchen.de/5904/1/5904.pdf Gerbes, Alexander L.; McEnroe, G. A.; Vollmar, Angelika M.; Kollenda, Margit C.
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