Freely Filtered, a NephJC Podcast

The Filtered Fragments (OG Filtrate) Joel Topf Jennie Lin Swapnil Hiremath Special Guest Brad Rovin [https://wexnermedical.osu.edu/find-a-doctor/brad-rovin-md-1348] GN God and second author from The Ohio State Koyal Jain [https://www.med.unc.edu/medicine/nephrology-hypertension/people/koyal-jain/] GN Specialist from UNC Alfred Kim [https://physicians.wustl.edu/people/alfred-kim-md-phd/] Rheumatologist from Washington University Editing by Simon Topf and Nayan Arora The Kidney Connection written and performed by by Tim Yau Show Notes Joel’s monologue One of the most surprising facts of nephrology is that despite conventional wisdom that lupus nephritis is an antibody mediated disease, that over a decade ago, the LUNAR investigtors were unable to find a significant benefit when rituximab was added to conventional therapy. And this was after the equally negative phase 2 trial of rituximab, EXPLORER. In fact, despite this finding rituximab has been able to burough its way into treatment of many nephrologists and rheumatologists as well as the KDIGO guidelines where it is suggested for patients with persistent disease activity or inadequate response to initial standard-of-care therapy. This long conflict is now coming to an end. Obinutuzumab, a newer, better monoclonal antibody targeting the same CD20 that we grew to love with rituximab, but it has a number of advantages. One. It is humanized antibody rather than a chimeric mouse-human antibody Two. It’s cytotoxicity is not complement dependent an particular advantage if you want to deploy it ina disease where hypocomplementemia is a disease characteristic Three, and most importantly, it causes stronger and deeper b-cell depletion than rituximab. Better B-cell depletion in the blood and tissue. And this brings us to tonight’s topic, we had already seen the phase two results of obinutuzumab which, unlike EXPLORER, were positive, we will look at the phase three  regency trial. This makes the third novel lupus nephritis drug in the last 4 years. We continue to remake glomerular nephritis. LUNAR: Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study Pubmed [https://pubmed.ncbi.nlm.nih.gov/22231479/] EXPLORER: Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial Pubmed [https://pubmed.ncbi.nlm.nih.gov/20039413/] REGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM [https://www.nejm.org/doi/full/10.1056/NEJMoa2410965] | NephJC [https://www.nephjc.com/news/regency-obi-ln-prnn2] NOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic Disease [https://ard.bmj.com/content/81/1/100] Comparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed Central [https://pmc.ncbi.nlm.nih.gov/articles/PMC5054300/] Class 5 lupus nephritis is slow to respond Long-term Use of Voclosporin in Patients with Class V Lupus Nephritis: Results from the AURORA 2 Continuation Study ACR Meeting abstract [https://acrabstracts.org/abstract/long-term-use-of-voclosporin-in-patients-with-class-v-lupus-nephritis-results-from-the-aurora-2-continuation-study/#:~:text=Patients%20with%20Class%20V%20lupus%20nephritis%20may,reduce%20proteinuria%20in%20this%20population%20are%20needed.&text=Conclusion:%20Voclosporin%2Dtreated%20patients%20with%20pure%20and%20mixed,treated%20with%20MMF%20and%20low%2Ddose%20steroids%20alone.] Tubular Secretions Swap: Young Adult novel I Must Betray You by Ruta Sepetys (Amazon [https://www.amazon.com/Must-Betray-You-Ruta-Sepetys/dp/1984836048/ref=asc_df_1984836048?mcid=d3c09a725eca38d8b48ee05239b1adff&hvocijid=11413289357258037967-1984836048-&hvexpln=73&tag=hyprod-20&linkCode=df0&hvadid=721245378154&hvpos=&hvnetw=g&hvrand=11413289357258037967&hvpone=&hvptwo=&hvqmt=&hvdev=c&hvdvcmdl=&hvlocint=&hvlocphy=9016826&hvtargid=pla-2281435179778&psc=1]) Koyal: Taekwondo (Wikipedia [https://en.wikipedia.org/wiki/Taekwondo]) Jennie: these unprecedented times Trump NYT: Administration Freezes $1 Billion for Cornell and $790 Million for Northwestern, Officials Say [https://www.nytimes.com/2025/04/08/us/politics/cornell-northwestern-university-funds-trump.html] Al: Acquired Podcast [https://www.acquired.fm] Brad: The Feather Thief by Kirk Wallace Johnson (Amazon [https://www.amazon.com/Feather-Thief-Obsession-Natural-History/dp/110198161X]) Joel: Paradise on Hulu (Wikipedia [https://en.wikipedia.org/wiki/Paradise_(2025_TV_series)])

The Filtrate Joel Topf Jordy Cohen Nayan Arora Special Guest Katie Kwon @katiekwonmd.bsky.social [https://bsky.app/profile/katiekwonmd.bsky.social] Mariana Murea @MarianaMurea [https://x.com/MarianaMurea] Editing by Simon Topf and Joel Topf Show Notes NephMadness at AJKDblog.org [https://ajkdblog.org] The Hemodialysis Region [https://ajkdblog.org/2025/03/01/nephmadness-2025-hemodialysis-region/] Vote for your favorites [https://www.tourneytopia.com/AJKD/NephMadness/SubmitPicks/Picks.aspx]

The Filtrate Joel Topf Swapnil Hiremath AC Gomez Sopia Ambruso Nayan Arora Special Guests Michelle Rheault [https://med.umn.edu/bio/michelle-rheault], Director, Division of Pediatric Nephrology, Professor of Medicine Tiffany Caza [https://www.arkanalabs.com/doctor/tiffany-caza/], Nephropathologist, Scientist and self-described Freely Filtered fan girl Editing by Simon Topf and Sophia Ambruso Show Notes 10. Healthcare Cyberattacks 9. ApoE in C3 glomerulonephropathy 8. Workforce woes in Adult and Pediatric Nephrology 7. Hyponatremia correction meta-analysis 6. Microvascular inflammation increases risk of graft loss - in all of its forms 5. Xenotransplantation 4. KDIGO CKD Guidelines 3. Hypertension control trials (ESPRIT, BPROAD) 2. The Renaissance of IgAN: IgAN treatment trials 1. FLOW: GLP-1 RAs in CKD

The Filtrate Joel Topf Swapnil Hiremath AC Gomez Jordy Cohen Nayan Arora Special Guest Brendon Nuen Editing by Simon Topf and Nayan Arora Show Notes FINEARTS-HF in NEJM [https://www.nejm.org/doi/full/10.1056/NEJMoa2407107] FINEARTS Kidney outcomes in JACC [https://www.jacc.org/doi/10.1016/j.jacc.2024.10.091] FINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes in Nature Medicine [https://pubmed.ncbi.nlm.nih.gov/39218030/] discussion in NephJC [/news/fineheart] BARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine [https://Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial]) Live Freely Filtered [/freelyfiltered/2024/11/4/nephjc-night-with-the-annual-kidney-week-with] at KidneyWk Swapnil comes out as a SpiroStan [http://www.nephjc.com/news/2024/10/8/finearts-comment] post to NephJC [/news/fineheart] TOPCAT TOPCAT primary publication [https://pubmed.ncbi.nlm.nih.gov/24716680/ ] TOPCAT North American results [https://www.ahajournals.org/doi/10.1161/circulationaha.114.013255] TOPCAT funny business explained [https://evidence.nejm.org/doi/full/10.1056/EVIDctcs2100007] AHA/ACC/HFSA Heart Failure Guidelines (PDF [https://www.ahajournals.org/doi/epdf/10.1161/CIR.0000000000001063]) SGLT2i are 2a MRA are a 2b ARBs are a 2b ARNI are a 2b Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone [https://www.jacc.org/doi/10.1016/j.jchf.2019.09.009] Kansas city cardiomyopathy questionnaire in patients with CKD without a diagnosis of heart failure: https://pubmed.ncbi.nlm.nih.gov/21187260/ [https://pubmed.ncbi.nlm.nih.gov/21187260/] GFR slope with steroidal MRAs in HF: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2635 [https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2635] Why Has it Been Challenging to Modify Kidney Disease Progression in Patients With Heart Failure? (JACC [https://www.sciencedirect.com/science/article/abs/pii/S0735109724082421]) Tubular Secretions Swap: Disclaimer [https://www.imdb.com/title/tt16294384/] on Apple TV AC: Duo Lingo Plushy (Amazon [https://www.amazon.com/STEZYO-Green-Stuffed-Animal-Pillow/dp/B0DLVZTVMJ/]) Nayan: The Puzzle Box [https://www.amazon.com/Puzzle-Box-Novel-Danielle-Trussoni/dp/0593595327] Jordy: Project Hail Mary [https://www.amazon.com/Project-Hail-Mary-Andy-Weir-ebook/dp/B08FHBV4ZX/ref=sr_1_1?crid=1CN5OPF1QIBKN&dib=eyJ2IjoiMSJ9.i39fitCkYicWa9gX8GAdKxoVxpElB8mxoYx9EBFDJNkbLRvVESbIVvBxAYO0r86R1mp-asOjY-WVpdgGh7jjQXdNGY0PKD3VMt6fQyvkJVardTCMCV2GmpAEjznQYgD_lr-P-pxBit0qs1EMrM-4vdH4mNV9cPYAC0SHc0P3uLB4G0gIMhUZXxmgSU4fhzw4tU35QvqDTG0_vHdt9v0uWrIdvD_32dkLE9AsMT6E8Ww.tDLLQDEqVjxZYiKxQeLQuT0oj-B1CW7qfirqZacTrjg&dib_tag=se&keywords=Project+Hail+Mary&qid=1734256891&s=books&sprefix=project+hail+mary%2Cstripbooks%2C206&sr=1-1] Brendon has a podcast, The Kidney Compass [https://www.hcplive.com/podcasts/kidney-compass] with Shikha Wadhwani. And he recommends singer-songwriter, Maggie Rogers (YouTube [https://www.youtube.com/channel/UCteFOtSvvbnceka5zKsHBYw]) Joel: The Singularity Is Nearer: When We Merge with AI [https://www.amazon.com/Singularity-Nearer-Ray-Kurzweil-ebook/dp/B08Y6FYJVY/ref=sr_1_1?crid=22VE2DWC30T3K&dib=eyJ2IjoiMSJ9.pr6ZjvXJPBieVYuMTBoCKNDIErffj6ZIho-wgKAp2g1AOECA5d3H560op0lFR2s5lJc1SCV1WiLguDBZ3J9aFSX8cLul4V7VjUIKuZ4wVkhaiZwGw94uGjew0OBvsnBjyPG3Q5QXnan2o4AnGKF1jxzlsWdecsVv3R4ZosIVqfvhlWdGCCGP-pWQvQS_JDOPJNrqySnCVNMGnT0jsgb4xsnGpKqkMxzhBlnMZlkNGGM.UrZ0BZR1XAoepCRh0o_efS_YCt1OFDwJZyd-3SlB3lA&dib_tag=se&keywords=The+Singularity+is+Nearer+Ray+Kurzweil&qid=1734257042&s=books&sprefix=the+singularity+is+nearer+ray+kurzweil%2Cstripbooks%2C356&sr=1-1] by Ray Kurzweil Closing music, Tim Yau with The Kidney Connection

The Filtrate: Joel Topf Swapnil Hiremath With Special Guest: Michelle Hladunewich, Nephrologist at the University of Toronto Mir Melamed, Maternal-Fetal Medicine at the University of Toronto Editor Simon Topf Show Notes Priscilla Smith’s letter: Dear Joel and the Freely Filtered team, I am a long-time fan of your podcast and was looking forward to hearing your recently aired discussion of the Praecis study of sflt1:PlGF use in preeclampsia. Preeclampsia and renal disease in pregnancy are areas that many nephrologists report a lack of knowledge or confidence in discussing and managing. I am a nephrologist who has been co-leading a renal pregnancy clinic in London while writing a PhD on progression of renal disease in pregnancy. I have had the immense privilege of working with experts and key opinion leaders in preeclampsia research both in the UK and internationally. As you know, preeclampsia is a serious and significant condition contributing to global maternal mortality and is also associated with future CKD and CVD risk so is both relevant and important within our professional group. Sadly, I found myself disappointed by the episode and felt it was a missed opportunity. I appreciate that you had difficulties obtaining appropriate experts to join the discussion, but perhaps it would have been better to delay production. While you all valiantly proceeded to discuss this important study, the topic is complex and there appeared to be a lack of understanding of the surrounding literature and pathogenesis of preeclampsia. Sadly, the maternal medicine expert’s comments at the end of the podcast added little as she seemed determine to negate any benefit from the results despite declaring she had no experience or expertise in the use of these biomarkers. There are many people who understand the clinical aspects of preeclampsia as well as having direct experience of the use and utility of these biomarkers who would have been able to contribute much to your conversation. I look forward to future discussions of renal disease in pregnancy on your podcast and would be happy to suggest some expert panellists if you ever find yourself stuck. Kind regards, Priscilla Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia (JCI 2003 [https://www.jci.org/articles/view/17189]) sFlt background: Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta (PubMed [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357118/]) PlGF background: Perspectives on the Use of Placental Growth Factor (PlGF) in the Prediction and Diagnosis of Pre-Eclampsia: Recent Insights and Future Steps (PubMed [https://pubmed.ncbi.nlm.nih.gov/36816456/]) The PRAECIS trial (NephJC [http://www.nephjc.com/news/praecis-preeclampsia] | NEJM Evidence [https://pubmed.ncbi.nlm.nih.gov/38319832/])