FF 87 Can Fish Oil Knock the Crap out of Dialysis Associated CV Disease?

The FiltrateJoel Topf‍ ‍@kidneyboy.bsky.social‬ (COI)Swapnil Hiremath @hswapnil.medsky.social and on LinkedInPedro Teixeira @nephcrit.bsky.socialSpecial Guests Charmaine E Lok, MD Professor of Medicine at the Faculty of Medicine, University of TorontoEditing and Show Notes byJoel TopfThe Kidney Connection written and performed by Tim YauShow NotesFish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis NEJM | NephJCWhat works in hemodialysis?Iron: PIVOTAL Trial (NEJM)Hemodiafiltration: CONVINCE (NEJM)That’s the whole listEarlier work on vascular access, The FISH Trial: Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial JAMAEskimo myth: "Fishing" for the origins of the "Eskimos and heart disease" story: facts or wishful thinking? (PubMed)Dialysis patients have low levels of fish oil in their body (PubMedCentral)Positive trial in non-dialysis patients: REDUCE-ITNegative trial of fish oil in non-dialysis patients: STRENGTHACC does not recommend FISH Oil for primary or secondary prevention of CV events (ACC)Poisson distribution (Wikipedia)Ocean Nutrition Canada (Wikipedia)Ocean Nutrition was bought by DSM (Press Release)DSM merged with Firmenich (Press Release)Vanguard feasibility trials (PubMed)Freezing fish oil caps will eliminate the fishy aftertaste (Pharmacists Letter)The study also received a philanthropic donation from Mr. Alexander Epstein (UHN Research)Selection Bias, Interventions and Outcomes for Survivors of Cardiac Arrest (PubMedCentral)Effectiveness of fish oil in controlling inflammation in adult patients undergoing hemodialysis: A systematic review and meta-analysis (PubMed)Tubular SecretionsSwapnil Hiremath: Michael Clayton (IMDB)Pedro: Fifa World Cup Soccer coming to North America with Portugal! (FIFA)Charmaine: New Puppy, Rose. It’s a Barbet (Wikipedia)Joel Topf: The Dark Forrest by Liu Cixin (Wikipedia)

The FiltrateJoel Topf‍ ‍@kidneyboy.bsky.social‬ (COI)Sophia Ambruso @sophia-kidney.bsky.socialSwapnil Hiremath @hswapnil.medsky.social and on LinkedInSpecial Guests Jonathan Barratt Professor of Renal Medicine, University of Leicester Google Scholar (COI: all the companies)Editing and Show Notes byNayan Arora @captainchloride.bsky.socialThe Kidney Connection written and performed by Tim YauShow NotesProteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy (Aliza Thompson, 2019 PubMed)The number, quality, and coverage of randomized controlled trials in nephrology (PubMed 2004)Updated here (PubMed | NephJC discussion)A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction (PubMed 2017)BLISS Belimumab in lupus nephritis (NephJC | PubMed) The Phase 2 trial of atacicept A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy (PubMed)The phase 3 trial of atacicept, the subject of this podcast A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy (PubMed | NephJC)Christos’ Bluesky post:https://bsky.app/profile/christosargyrop.bsky.social/post/3m5bsujwg3s2q The use of Gd-IgA1 in the Testing Trial Role of Systemic Glucocorticoids in Reducing IgA and Galactose-Deficient IgA1 Levels in IgA Nephropathy (PubMed)If you can’t get enough Jon Barratt, take a look at his grand rounds at The University of Ottawa. Updates to the KDIGO Guidelines for the treatment of IgA nephropathy, with Prof Jonathan Barratt (YouTube)Tubular SecretionSwapnil Hiremath Pluribus on Apple TV (Wikipedia)Jon Barratt Lynyrd Skynyrd (Wikipedia) Slow Horses (Wikipedia) on AppleTVJoel Topf the new ASN

The FiltrateJoel Topf‍ ‍@kidneyboy.bsky.social‬Sophia Ambruso @sophia-kidney.bsky.socialNayan Arora @captainchloride.bsky.socialSpecial Guests Brian Rifkin @brianrifkin.bsky.socialAnna Gaddy @AnnaGaddyEditing and Show Notes byJoel TopfThe Kidney Connection written and performed by Tim YauShow NotesBrian Rifkin and Cristina Popa ascend to co-editors in chief of NephJC.Paresh Jadav receives the first NephJC Champion award. Dr. Jadav hosted the NephJC night and saved NephJC thousands of dollars. It makes a huge difference in our fund raising. Thank you.Also a big thank-you to Jade Teakell for buying the cowboy hats!The first pick of the draft, by Sophia is Fish oil for dialysis: Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis (NEJM)The second pick, by Brian is FINE-ONE (Bayer Press release)Rajiv Agarwal’s mediation analysis to show how much of finerenone’s beneficial renal effects are captured by the reduction proteinuria: Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis (PubMed)Anna has the third pick and it goes to Katherine Tuttle and the REM0DEL Trial: REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide (Science Direct)Nayan goes off-board and picks a poster by a med student (backed by Testani)Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure (ClinicalTrials.gov)For the final pick in the draft Joel went with a little Lilly on Lilly violence: Tirzepatide vs. Dulaglutide Is Associated with Reduced Major Kidney Events in Patients with Type 2 Diabetes, CVD, and Very High-Risk Kidney Diseases (JASN)Bring out your dead…What’s left on the draft board.Liberate-D A Conservative Dialysis Strategy and Kidney Function Recovery in Dialysis-Requiring Acute Kidney Injury: The Liberation From Acute Dialysis (LIBERATE-D) Randomized Clinical Trial (JAMA)Atacicept for IgAN A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy (NEJM)Lilia Cervantes crushed it with Community Health Worker Support for Hispanic and Latino Individuals Receiving Hemodialysis: The Navigate-Kidney Randomized Clinical Trial (JAMA)Tubular SecretionBrian: Late Breaking and High Impact Clinical Trials. Including Sibe! REGENCY Biopsy Data.Sophia: Flying Home. No, really it’s the Electrolyte QuizJoel: The Poster Session, the Quiz Session, and Nayan: Flying to AHA to talk about dual-heart-kidney-transplantAnna: Kidney STARS! and Melanie Hoenig’s session on potassium

The FiltrateJoel Topf‍ ‍@kidneyboy.bsky.social‬Swapnil [email protected] @medpeedskidneys.bsky.socialSpecial GuestMike Walsh Associate Professor in the Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University as well as a Scientist at the Population Health Research Institute and a nephrologist at St. Joseph’s Healthcare Hamilton where he is the Chair of the Clinical Nephrology Research Group. Editing and Show Notes bySophia AmbrusoThe Kidney Connection written and performed by Tim YauShow NotesALCHEMIST (NephJC Shorts, Rossignol et al Lancet 2025)AC is in her 83rd year of med-peds fellowship.Joel’s monologue brings us all down.Prophylactic ICD therapy doesn’t improve sudden cardiac death or all-cause mortality in HD patients in the ICD2 trial (Jukema JW et al. Circulation 2019)Initiation with statins do not impact MACE endpoints or atherosclerotic events (4D AURORA trial Fellstrom BC et al. NEJM 2009 & SHARP trial Baigent C et al. Lancet 2011)Mike tries to liven up the mood by mentioning positive outcomes with iron therapy in heart failure with the PIVOTAL trial (Macdougall IC et al. NEJM 2018)TOPHAT trial revealed treatment with spironolactone in HFpEF did not affect MACE outcomes. (Pitt B et al. NEJM 2014)NephTrials ‘Run-in periods in clinical trials: What can we ACHIEVE?’SPIN D trial - spironolactone dose finding trial in ESRD (Charytan DM et al. Kidney Int 2018)Mike shares the human experience of the trial after being instructed to end the trial prematurely and being told they have “answered their question”Study in Japan - spironolactone predominantly benefits male over females (cannot find this)Male vs female benefit not observed in ACHIEVE despite Mike’s initial hypothesisSwap compares and contrasts ACHIEVE, ALCHEMIST & Meta-analysis (Pyne L et al. Lancet 2025)Mike discusses how nonadherence to spironolactone impacted the intention to treat outcomes in the trial.What is a high risk of bias for dummies?Mike, Swap & Joel ponder future nsMRA or ASI trials hemodialysis?Tubular secretionsSwap is probably stalking Martha Wells by now, has moved on from Witch King, now onto Queen Demon on Good ReadsAC is adding to her brood, 2 dogs (Snickers & Harper), 1 childDungeon Crawler Call -  a science fantasy book series by Matt Dinniman (on goodreads), which he lovingly referred to as complete nerd trash.Joel is binging on the series Task on HBO max, featuring Mark Ruffalo as FBI agent.NephJC is having its annual fundraiser (get your tickets here) at ASN. Providing a party shuttle that is leaving every 30 minutes from the conference center. As always, it will feature a live podcast recording covering the ASN late breaking, high impact clinical trials.Swap describes the high impact model at ASN this year - go big or go home.

The FiltrateJoel Topf @kidneyboy.bsky.social‬Swapnil Hiremath @hswapnil.medsky.socialNayan Arora captainchloride.bsky.socialSopia Ambruso @sophia-kidney.bsky.socialSpecial Guests Brendon Neuen @brendonneuen.bsky.social Associate Professor and Program Lead, Renal and Metabolic at The George Institute for Global Health. Nephrologist and Director of Kidney Trials at Royal North Shore Hospital.Neuen has had three prior appearances on Freely Filtered: EMPA Kidney, DUPLEX and Sparsentan in FSGS, FLOW and SemaglutideMuthiah Vaduganathan @mvaduganathan on X. Cardiologist at Brigham and Women's Hospital and Harvard Medical School. Assistant Professor of Medicine.Editing byJoel TopfThe Kidney Connection written and performed by Tim YauShow NotesDONATE to NephJC! Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes NEJM | NephJC SummaryFIDELIO Bakris et al, NEJM 2020 | NephJC Summary; subgroup throws doubt on efficacy of finerenone in patients on flozinsFIGARO Pitt et al, NEJM 2021; subgroups clearly shows finerenone works, flozins or notNEJM editorial (wrongly) saying do not use Flozins unless on RASi Don’t use dual RAS blockade ONTARGET Yusuf et al, NEJM 2008; VA NEPHRON-D Fried et al NEJM 2013Why we cannot study finerenone in HFrEF (RALES Pitt et al NEJM 1999) Muthu is jealous of GFR slope and albuminuria surrogate endpoints and wants to borrow them for HFpEF (Inker et al EHJ 2025)Combination therapy and CV outcomes in hypertension (Wang et al JAMA Card 2024 on low dose combinations and BP; Egan et al Blood Pressure 2022 review of topic) CONFIRMATION HF trial registry entry (Finerenone and Empagliflozin in hospitalized patients with HF)23:20: Nayan and Swap miss a chance to say ‘de-flozination’ to discuss stopping a flozin which would allow a patient to be included in the trial Finerenone is a CYP3A4 substrate (Heinig et al Clin Pharmacokinetics 2023); Useful list of CYP3A4 inducers and inhibitors Everyone should get an ABPM (Bugeja et al CMAJ 2022)EASiKIDNEY study design Albuminuria mediates CKD benefits with Finerenone (Agarwal et al Ann Intern Med 2023)GFR slope and Albuminuria and the FDA (Taylor et al eClin Med 2025) Dapagliflozin and Eplerenone combination crossover trial (Provenzano et al JASN 2022)Joel gets promoted! (PBFluids reflection) Bluesky NephJC Chat discussion on ‘renal remission’ Withdrawal of Finerenone and worse outcomes from FINEARTS (Vaduganathan et al JACC 2025)Combination therapies Analysis from Brendan and Muthu (Neuen et al Circulation 2024)Do not use KFRE when GFR > 60 (KDIGO Practice Point 2.2.4: Note that risk prediction equations developed for use in people with CKD G3–G5, may not be valid for use in those with CKD G1–G2) Finerenone vs Spironolactone trial in Primary Aldosteronism (Hu et al Circulation 2025)FIND CKD trial design (Heerspink et al NDT 2025) FINE-ONE trial design (Heerspink et al Diab Res Practice 2023) Tubular SecretionsNayan keeping his chin up as Yankees lose and Mariners follow (MLB Playoffs)Sophia’s adventures with Beekeeping (Royal Jelly?) Brendon loves listening to ‘Susan’ by Raye Muthu is back into Taekwondo Swap is still reading Martha Wells (Witch King on GoodReads)Joel will be hiking the Laugavegur trail in Iceland 

The FiltrateJoel Topf Bluesky: @kidneyboy.bsky.social‬Jordy Cohen Bluesky: @jordybc.bsky.social‬Swapnil Hiremath Bluesky: @hswapnil.medsky.social‬Special Guest Edouard “call me Ed” Fu Assistant Professor and Medical Student, and second author of his second paper covered on NephJC. LinkedIn | Leiden University Medical CenterEditing bySimon Topf and Sophia AmbrusoThe Kidney Connection written and performed by by Tim YauShow NotesEd’s first paper on NephJC: Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study (NephJC | BMJ)Phenformin Wikipedia | Boca Raton NewsThe metformin black box (as part of the FDA Label)WARNING: LACTIC ACIDOSISPostmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see PRECAUTIONS).Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and PRECAUTIONS).If metformin-associated lactic acidosis is suspected, immediately discontinue metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS).Target Trial Emulation A Framework for Causal Inference From Observational Data. Miguel A. Hernán, MD, DrPH; Wei Wang, PhD; David E. Leaf, MD JAMA 2022Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study (NephJC | PubMed)Toxicokinetics of Metformin During Hemodialysis (KI Reports)Metformin in People With Diabetes and Advanced CKD: Should We Dare? Editorial that ran in AJKD along side the Lambourg manuscript (AJKD)Immortal Time Bias in Cohort Studies of Kidney Transplant Recipients (Kim SJ Amer J Trans 2010)Ed’s Target trial review in JASN which Jordy mentioned and includes an explanation of the obesity paradox by depletion of the susceptibles. (Fu JASN 2023)Ed’s Grand Rounds at Ottawa on YouTube. Very good.Response by Cohen et al to Letter Regarding Article, “Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19” by Jordy and the crew Circ Res 2000Review article on the issue: Evaluating sources of bias in observational studies of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use during COVID-19: beyond confounding Jordy and a different crew J Hyperten 2021Figure S5: Weighted cumulative incidence curves for MACE, by treatment strategyThe S4 image that Swap lovedTubular SecretionsJordy Andor Season 2 on Disney+ (Wikipedia)Swapnil Murderbot on Apple TV+ (Wikipedia)Eduoard: New house and grant Grant Grant (Wikipedia)Joel Topf Three Body Problem Audio book (Audible)

One of NephJC signature moves has been to adapt new technologies and communication techniques to delivering state of the art nephrology education. Podcasts, Visual Abstracts, Tweetorials. NephJC has been on the front of these waves. Clearly one of the most exciting and controversial new technologies is artificial intelligence and it is unclear what role it may play in the NephJC educational package. Our blogs and tweets are written entirely by human minds but it is inevitable that as AI becomes the spellcheck of the 2020s, that it will leach into all of our writing. One AI tool that intrigues us is Google’s NotebookLM. This product can create podcasts from source documentation. We plan on publishing a podcast before each chat. We are fact checking them before publication, but some mistakes may slip through. Please send you feedback, we want to know what you think of this. As always, the email is [email protected] will supplement and not replace Freely Filtered. One possible future move is to separate out both podcasts to individual feeds, but for now they will piggyback on each other.

One of NephJC signature moves has been to adapt new technologies and communication techniques to delivering state of the art nephrology education. Podcasts, Visual Abstracts, Tweetorials. NephJC has been on the front of these waves. Clearly one of the most exciting and controversial new technologies is artificial intelligence and it is unclear what role it may play in the NephJC educational package. Our blogs and tweets are written entirely by human minds but it is inevitable that as AI becomes the spellcheck of the 2020s, that it will leach into all of our writing. One AI tool that intrigues us is Google’s NotebookLM. This product can create podcasts from source documentation. We have done a couple of dry runs converting our blogs into novel, low-effort, podcasts with impressive results. So, at least for now, we plan on publishing a podcast before each chat. We are fact checking them before publication, but some mistakes may slip through. Please send you feedback, we want to know what you think of this. As always, the email is [email protected] will supplement and not replace Freely Filtered. One possible future move is to separate out both podcasts to individual feeds, but for now they will piggyback on each other.

The FiltrateJoel TopfAC GomezSophia AmbrusoNayan AroraSpecial Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/HypertensionExtra-Special GuestMichelle Rheault, MD Professor of Pediatrics, University of MinnesotaEditing bySimon and Joel TopfThe Kidney Connection written and performed by by Tim YauShow NotesKDIGO ADPKD Guidelines:WebsiteGuideline PDFExecutive Summary PDFNephJC coverageConsortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)Hy’s Law (Wikipedia) has three components:ALT or AST by 3-fold or greater above the upper limit of normalAnd total serum bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal)And no other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injuryMeeting this definition yields a very high risk of fulminant kidney failure (76% in one series)Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database (PubMed) Two of 957 patients on tolvaptan met Hy’s law criteria. None had fulminant kidney failure.Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial (PubMed) Patients had a baseline urine volume on tolvaptan of 6.9 L/24 h. Urine volume decreased to 5.1 L/24 h with hydrochlorothiazide and to 5.4 L/24 h on metformin.TEMPO 3:4 Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease (NEJM)Reprise Trial Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease ( NEJM | NephJC )Unified ultrasonographic diagnostic criteria for polycystic kidney disease by Edelstein in JASN (PubMed)Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies (PubMed)Charles’ draft choice Recommendation 4.1.1.1: We recommend initiating tolvaptan treatment in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ‡25 ml/min per 1.73 m2 who are at risk for rapidly progressive disease (1B).Sophia’s draft choice Recommendation 1.4.2.1: We recommend employing the Mayo Imaging Classi cation (MIC) to predict future decline in kidney function and the timing of kidney failure (1B).Progression to kidney failure in ADPKD: the PROPKD score underestimates the risk assessed by the Mayo imaging classification (Frontiers of Science)AC’s draft choice Recommendation 9.2.1: We recommend targeting BP to ≤ 50th percentile for age, sex, and height or ≤ 110/70 mm Hg in adolescents in the setting of ADPKD and high BP (1D).HALT-PKD Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease (NEJM)Nayan’s draft choice Recommendation 6.1.2: We recommend screening for ICA in people with ADPKD and a personal history of SAH or a positive family history of ICA, SAH, or unexplained sudden death in those eligible for treatment and who have a reasonable life expectancy (1D).Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease (CJASN)Surgical Clipping Versus Endovascular Coiling in the Management of Intracranial Aneurysms (PubMed) Clipping is associated with a higher rate of occlusion of the aneurysm and lower rates of residual and recurrent aneurysms, whereas coiling is associated with lower morbidity and mortality and a better postoperative course.Joel’s editorial pick Recommendation 6.1.1: We recommend informing adults with ADPKD about the increased risk for intracranial aneurysms (ICAs) and subarachnoid hemorrhage (1C).Joel’s first draft pick The bring out your dead pick:Recommendation 4.3.1: We recommend not using mammalian target of rapamycin (mTOR) inhibitors to slow kidney disease progression in people with ADPKD (1C).Recommendation 4.4.1: We suggest not using statins specfiically to slow kidney disease progression in people with ADPKD (2D).Recommendation 4.5.1: We recommend not using metformin specifically to slow the rate of disease progression in people with ADPKD who do not have diabetes (1B).Recommendation 4.6.1: We suggest that somatostatin analogues should not be prescribed for the sole purpose of decreasing eGFR decline in people with ADPKD (2B).Perfect match: mTOR inhibitors and tuberous sclerosis complex (Orphanet Journal of Rare Diseases)Navitor Pharmaceuticals Announces Janssen Has Acquired Anakuria Therapeutics, Inc. (BioSpace) This is press release about acquiring the mTor1 inhibitor.Joel’s second draft pick Recommendation 4.2.1.1: We suggest adapting water intake, spread throughout the day, to achieve at least 2–3 liters of water intake per day in people with ADPKD and an eGFR ≥ 30 ml/min per 1.73 m2 without contraindications to excreting a solute load (2D).Nayan’s bonus draft Practice Point 4.7.1: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) should not be used to slow eGFR decline in people with ADPKD.Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan (KIReports)SMART Trial of GLP-1ra in non-diabetics: Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial (PubMed)Tubular SecretionsNayan: Landman on Paramount Plus (IMDB)Sophia: PassNayan: steps in with The Pitt on HBO (Wikipedia)Charles: The White Lotus, Yellowstone 1923, Poirot (IMDB)AC: The PittMichael Crichton’s Estate Sends The Pitt to the Courtroom (Vulture)Joel: I Must Betray you by Ruta Sepetys (Amazon)

The Filtered Fragments (OG Filtrate)Joel TopfJennie LinSwapnil HiremathSpecial Guest Brad Rovin GN God and second author from The Ohio StateKoyal Jain GN Specialist from UNCAlfred Kim Rheumatologist from Washington UniversityEditing bySimon Topf and Nayan AroraThe Kidney Connection written and performed by by Tim YauShow NotesJoel’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 antibodyTwo. It’s cytotoxicity is not complement dependent an particular advantage if you want to deploy it ina disease where hypocomplementemia is a disease characteristicThree, 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 PubmedEXPLORER: 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 PubmedREGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM | NephJCNOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic DiseaseComparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed CentralClass 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 abstractTubular SecretionsSwap: Young Adult novel I Must Betray You by Ruta Sepetys (Amazon)Koyal: Taekwondo (Wikipedia)Jennie: these unprecedented times Trump NYT: Administration Freezes $1 Billion for Cornell and $790 Million for Northwestern, Officials SayAl: Acquired PodcastBrad: The Feather Thief by Kirk Wallace Johnson (Amazon)Joel: Paradise on Hulu (Wikipedia)