Freely Filtered, a NephJC Podcast

The FiltrateJoel Topf kidneyboy.bsky.socialPedro Teixeira @nephcrit.bsky.socialNayan Arora @captainchloride.bsky.socialAnna Gaddy @annagaddy.bsky.social Swapnil Hiremath @hswapnil.medsky.social and on LinkedInSpecial GuestsIan McCoy, MD @NephroNinja study author and UCSFChi-yuan Hsu Senior author and Chief of the Division of Nephrology at UCSFSamuel Silver Associate Professor at Queens University in CanadaEditingVipin Verghese and Joel TopfShow Notes NephJC Discusion: Dialyze Less, Recover More? AKI’s Chance to Get LIBERATE-DManuscript: A Conservative Dialysis Strategy and Kidney Function Recovery in Dialysis-Requiring Acute Kidney InjuryThe Liberation From Acute Dialysis (LIBERATE-D) Randomized Clinical Trial JAMA | PubMedBen’s pilot study: RAD-AKI Pilot study: Recovery After Dialysis-Requiring Acute Kidney Injury (RAD-AKI) (ClinicalTrials.gov)STARRT-AKI NephJC Editorial in JAMA: A-E-I-O-U and Sometimes Why—Dialysis in Acute Kidney Injury (JAMA)What Is Dialytrauma? (Nephrology Times)How Fragile Are the Results of a Trial? The Fragility Index (PubMedCentral)Shiffl Trial: Daily Hemodialysis and the Outcome of Acute Renal Failure (NEJM)AKIKI: Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit (NEJM)AKIKI2: How Late it was, How Late! (NephJC)Sam Silver’s study: Promoting Kidney Recovery After Acute Kidney Injury Receiving Dialysis (Recover-AKI) (ClinicalTrial.Gov)Marie Kondo (Wikipedia)Tubular SecretionsSwap: The smutty dragon novels of novels of Rebecca Yarros (Wikipedia) Specifically The Empyrean seriesAnna: Brisket recipesPedro: The Naked Gun (Wikipedia) with Liam NeesonIan: ASN Kidney Health Guidance on the Outpatient Management of Patients with Dialysis-Requiring Acute Kidney Injury (PubMed) he really doesn’t get Tubular Secretions.Nayan: Tilt: A Novel by Emma Pattee (Amazon)Chi: The Year of Magical Thinking by Joan Didion (Wikipedia) and Innovations in Nephrology (Springer Nature)Sam: Monopoly Super Electronic Banking Board Game (Amazon)Joel: Song Sung Blue (Wikipedia)

The FiltrateJoel Topf (kidneyboy.bsky.social)AC (@medpeedskidneys.bsky.social)NephMadnessAnna Gaddy (@AnnaGaddy) Vipin Verghese (@vipvargh.bsky.social) Natalie Freidin Program director at Medical University of South CarolinaSpecial GuestsAnna Vinnikova (@kidneywars.bsky.social) Long time game maker for NephMadness and Associate Professor at Virginia Commonwealth UniversityAutumn Harris Associate Professor of Veterinary Medicine at NC StateSarah Street MD PhD Assistant Professor of Medicine at Virginia Commonwealth UniversityEditingJoel TopfShow Notes Animal House scouting reportAutumn Harris on Team CatCheese!

I know 2026 feels like it ihas been here for months, but only a few weeks ago we were celebrating the nephrology accomplishments of 2025. The New Filtrate came together to review the year.The FiltrateJoel Topf‍ ‍@kidneyboy.bsky.social‬ (COI)Swapnil Hiremath @hswapnil.medsky.social and on LinkedIn Editor in Chief of Kidney International Case ReportsAnna Gaddy (@AnnaGaddy) Winner of NephJC Rookie of the Year 2020Nayan Arora (@CaptainChloride.bsky.social)AC (@medpeedskidneys.bsky.social)Vipin Verghese (@vipvargh.bsky.social) co-winner of NephJC Engaged Scientist of the Year in 2021Brian Rifkin (@brianrifkin.bsky.social) Co-Editor in Chief NephJC. Winner of NephJC Rookie of the Year 2021Cristina Popa (@NephroSeeker) Co-Editor in Chief NephJC. Wwinner of NephJC Rookie of the Year 2022 and MVP 2023Editing and Show Notes byAnna Gaddy and Joel TopfThe Kidney Connection written and performed by Tim YauShow NotesTop Stories in Nephrology 2025 (NephJC)First Top sories in Nephrology 2010! (Renal Fellow Network)Links to all of the Top Stories in Nephrology, hosted on NephJC since 2017 (NephJC)1. IgA NephropathyVISIONARY: Sibeprenlimab in IgA Nephropathy — Interim Analysis of a Phase 3 Trial (NEJM)ORIGIN 3: A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy (NEJM)APPLAUSE-IgA Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy (NEJM)Aliza M. Thompson, MD, MS (ASN) 2. Lupus NephritisREGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis (NEJM)3. Nobel prize winner and peripheral immune tolerance4. Xenotransplantation5. GLP1ra RevolutionRemodel REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide (Kidney International)SURPASS-CVOT Tirzepatide vs. Dulaglutide Is Associated with Reduced Major Kidney Events in Patients with Type 2 Diabetes, CVD, and Very High-Risk Kidney Diseases (Kidney Week abstract in JASN)Poll: 1 in 8 Adults Say They Are Currently Taking a GLP-1 Drug for Weight Loss, Diabetes or Another Condition, Even as Half Say the Drugs Are Difficult to Afford (KFF survey)6. GDMT implementation in CKD: lessons learnt from CONFIDENCE and MIRO-CKDConfidence Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes (NEJM)MIRO-CKD Balcinrenone in combination with dapagliflozin compared with dapagliflozin alone in patients with chronic kidney disease and albuminuria: a randomised, active-controlled double-blind, phase 2b clinical trial (The Lancet)7. Flozin Meta analysisSMART-C. SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria. A Meta-Analysis (JAMA)SMART-C. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria. A Meta-Analysis (JAMA)8. Paradigm Shift: Aiming for CKD Remission9. Fish Oil and DialysisPISCES Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis (NEJM)10. Decline in Dialysis Patients in the United StatesUSRD 2025 Annual Data Report (USRDS)Tubular SecretionSwapnil Hiremath Alien Earth on FX Hulu (Wikipedia)AC A Christmas Carol by Charles Dickens (Wikipedia) and The Muppet Christmas Carol (Wikipedia)Anna Monty Don (Wikipedia)Nayan Back Street Boys at The Sphere (Wikipedia)Brian Marty Supreme (Wikipedia)Cristina The Yellow Tie (Wikipedia)Vipin Stranger Things, good for a four year old? (Wikipedia)Joel Crash Course: The Universe with Katie Mack and John Green (Apple PodCasts)

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)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)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.social‬ (COI)Pedro Teixeira @nephcrit.bsky.socialAna Gaddy @AnnaGaddyNayan Arora @captainchloride.bsky.socialSpecial Guests David Goldfarb Professor of Medicene, NYU (COI)Editing byPedro TeixeiraThe Kidney Connection written and performed by Tim YauShow NotesBICARBICU 2018 (Lancet) BICARBICU-2 2025 (JAMA)SOFA score (Wikipedia)Sodium bicarbonate administration for metabolic acidosis in the intensive care unit: a target trial emulation (PubMed)Effect of sodium bicarbonate on intracellular pH under different buffering conditions (PubMed)Evaluating the clinical and cost-effectiveness of Sodium Bicarbonate administration for critically ill patients with Acute Kidney Injury (MOSAICC) (ICNARC Site)SODium BICarbonate for Metabolic Acidosis in the ICU (SODa-BIC) (ClinicalTrials.gov)Surviving Sepsis Campaign Guidelines 2021 (Website)Tubular SecretionsNayan: Louise Penny, The Black Wolf (Amazon)Anna: Broom Gate: A Curling Scandle (CBC) Pedro: One Battle After Another! (Wikipedia)David: Patti Smith (Wikipedia) Bonus pick: Kids Rarely Read Whole Books Anymore. Even in English Class. (NYT)Joel: Boys in the Boat by Daniel James Brown (Film Wikipedia | Book Wikipedia)

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 Hiremath@hswapnil.medsky.socialAC @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.social‬AC @medpeedskidneys.bsky.social‬Nayan Arora @captainchloride.bsky.social‬Special Guest Vandana Niyyar Professor of Medicine at Emory School of MedicineEditing byNayan AroraThe Kidney Connection written and performed by by Tim YauShow NotesAmerican Society of Diagnostic and Interventional Nephrology (Website)ASDIN List of training sitesPlacement, performance and complications of the Ash Split Cath hemodialysis catheter (PubMed)Platelet Function Assay FAQ (PDF)Saint Clair’s Vascular Access Center where we do outpatient biopsies (Website)The studies: NephJC Summary Prasad Study KI Reports Chakrabarti in Kidney 360Thromboelastogram (TEG) (Life in the Fastline)Elastigirl (Wikipedia)Association of Kidney Biopsy Needle Gauge with Post-Procedure Complications and Biopsy Adequacy (PubMed)Complications of Percutaneous Renal Biopsy (PubMed)Tubular SecretionsNayan Quarterback on Netflix (Wikipedia)AC The Rehearsal on HBO (Wikipedia)Joel The Detroit Tigers (MLB)

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)

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)

The FiltrateJoel TopfJordy CohenNayan AroraSpecial Guest Katie Kwon @katiekwonmd.bsky.socialMariana Murea @MarianaMureaEditing bySimon Topf and Joel TopfShow NotesNephMadness at AJKDblog.orgThe Hemodialysis RegionVote for your favorites

The FiltrateJoel TopfSwapnil HiremathAC GomezSopia AmbrusoNayan AroraSpecial Guests Michelle Rheault, Director, Division of Pediatric Nephrology, Professor of MedicineTiffany Caza, Nephropathologist, Scientist and self-described Freely Filtered fan girlEditing bySimon Topf and Sophia AmbrusoShow Notes10. Healthcare Cyberattacks9. ApoE in C3 glomerulonephropathy8. Workforce woes in Adult and Pediatric Nephrology7. Hyponatremia correction meta-analysis6. Microvascular inflammation increases risk of graft loss - in all of its forms5. Xenotransplantation4. KDIGO CKD Guidelines3. Hypertension control trials (ESPRIT, BPROAD)2. The Renaissance of IgAN: IgAN treatment trials1. FLOW: GLP-1 RAs in CKD

The FiltrateJoel TopfSwapnil HiremathAC GomezJordy CohenNayan AroraSpecial Guest Brendon NuenEditing bySimon Topf and Nayan AroraShow NotesFINEARTS-HF in NEJM FINEARTS Kidney outcomes in JACCFINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes in Nature Medicine discussion in NephJC BARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine)Live Freely Filtered at KidneyWkSwapnil comes out as a SpiroStan post to NephJC TOPCATTOPCAT primary publication TOPCAT North American results TOPCAT funny business explained AHA/ACC/HFSA Heart Failure Guidelines (PDF)SGLT2i are 2aMRA are a 2bARBs are a 2bARNI are a 2bClinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to SpironolactoneKansas city cardiomyopathy questionnaire in patients with CKD without a diagnosis of heart failure: https://pubmed.ncbi.nlm.nih.gov/21187260/GFR slope with steroidal MRAs in HF: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2635Why Has it Been Challenging to Modify Kidney Disease Progression in Patients With Heart Failure? (JACC)Tubular SecretionsSwap: Disclaimer on Apple TVAC: Duo Lingo Plushy (Amazon)Nayan: The Puzzle BoxJordy: Project Hail MaryBrendon has a podcast, The Kidney Compass with Shikha Wadhwani. And he recommends singer-songwriter, Maggie Rogers (YouTube)Joel: The Singularity Is Nearer: When We Merge with AI by Ray KurzweilClosing music, Tim Yau with The Kidney Connection

The Filtrate:Joel TopfSwapnil HiremathWith Special Guest:Michelle Hladunewich, Nephrologist at the University of TorontoMir Melamed, Maternal-Fetal Medicine at the University of TorontoEditor Simon TopfShow NotesPriscilla 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)sFlt background: Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta (PubMed)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)The PRAECIS trial (NephJC | NEJM Evidence)

We had a great NephJC get together. We recorded the whole event and packaged it into a podcast.Musical entertainmentTim Yau (@Maximal_Change)Too Sweet by HozierFairy Tale of New York by written Jem Finer and Shane MacGowan. Hear it performed by the Pogues.Interview of Tom MuellerTom Mueller author of How to Make a KillingJade Teakall@jmteakellGraham Abra@GrahamAbraInterview of Tom MuellerTom Mueller author of How to Make a KillingJade Teakall @jmteakellGraham Abra @GrahamAbraNephMadness logo revealNephJC KidneysNephJC blog postNephJC Manuscript of the Year: Flow accepted by Meg JardineManjula Kurella Tamura, winner of the 2015 NephMadness, oh and author of NEJM manuscripts and subject of a NYT article.NephJC Visual Abstract of the Year: Corina Teodusiu, creator of the Flozinator logoNephJC Social Justice Award: ISN petition to the WHO on Kidney HealthMost Engaged Scientist Award: Michelle RheaultRookie of the Year: Milagros FloresMVP: Christina PopaNephJC Founders Award: Joshua WaitzmanNathan Hellman Social Media Project of the Year: Edgar Lerma and the ASN Visual Abstract TeamMore Music with TimSaginaw, Michigan as performed by Johny CashBetty, written by Taylor SwiftThe Kidney ConnectionFreely Filtered Kidney Week DraftPrevious drafts2021 ASN Kidney Week Draft2022 ASN Kidney Week Draft2023 ASN Kidney Week DraftList of all the simultaneous publications from Kidney Week 2024Sophia: SMART Trial (Link goes to the new KidneyCompass podcast that interview lead author Hiddo HeerspinkJordy’s editorial in the European Heart Journal. LinkJosh: APPLAUSE Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy in the NEJMAPPLAUSE results announcement at The World Congress of Neophrology in Buenos AriesIptapocan is a factor B inhibitionJordy: POISE-3 with simultaneous publication in KIMentions she wanted to pick KAT-AKI because she worked with Perry Wilson.Per Nayan, Amit Garg is the Beyonce of NephrologyAccord Trial (NEJM)Joel: HSK21541 for PruritusCorrection link to source (graph)Nayan: FINEARTS-HF with simultaneous publication in JACCBARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine)Swapnil comes out as a SpiroStanTOPCAT funny businessPATHWAY-2 Trial (NephJC coverage)Swap: K Bath and cardiac arrhythmia with simultaneous publication in Kidney InternationalCAST: A study that rocked the cardiology world and became the poster child for evidence-based medicine (Link)Tubular SecretionsSwap: Late breaking and high impact sessionsNayan: Intro to…Joel: Student poster on blood pressure techniqueJordy: The Penguin. A couple of mentee postersSophie: Tracks her sessions on paper.Josh: Quiz and Questionaire session with JC Velez, Bea Concepcione, Anna Burgner, Roger Rodby.

The Filtrate:Jennie LinJoel TopfJosh WaitzmanSwapnil HiremathWith Special GuestsPedro TeixeiraJay KoynerEditor Sophia AmbrusoShow NotesThe article: A Randomized Trial of Intravenous Amino Acids for Kidney ProtectionNephJC SummaryKDIGO Clinical Practice Guideline for Acute Kidney Injury (PDF)Steve Coca study Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials (PubMed)Using Nephrocheck to prevent AKI: Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial (PubMed)Brenner’s Review of protein intake and renal hemodynamics: Dietary Protein Intake and the Progressive Nature of Kidney Disease: — The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Ablation, and Intrinsic Renal Disease (NEJM)Husain-Syed a look at preoperative renal functional reserve and risk of AKI: Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation (PubMed)Dana Fuhrman review of renal functional reserve: The Role of Renal Functional Reserve in Predicting Acute Kidney Injury (PubMed)Use of SGLT2i prevented AKI in the placebo controlled trials. Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 Individuals (PubMed)Assessment of P values for demographic data in randomized controlled trials (PubMed)Tubular SecretionsSwapnil The Lord of the Rings: Rings of Power Season 2 on Amazon Prime (Wikipedia)Josh Fortnite (Website)Pedro CRRT Academy at University of Alabama Birmingham (Website)Jay Koyner Slow Horses on AppleTV (Wikipedia)Jennie Linn #KidneyWk Run Club Friday 10/25 at 6:15 am PST Meet in front of Sally’s Fish House ~2 miles. Easy pace (10-12 min/mile) (Strava)Joel Topf Your Honor on Netflix (Wikipedia)