Freely Filtered, a NephJC Podcast

• FF 84 ACHIEVE: Spironolactone flops in dialysis

  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.

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• FF 83 CONFIDENCE: Can We Start Flozins and Finerenone Simultaneously?

  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

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• FF 81 Metformin Termination as explored by Target Trial Emulation

  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)

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• NephJC RoboPod Episode 2: The NUDGE Trial

  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.

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• NephJC RoboPod Episode 1: The Stamp Act Tac v MMF in Pediatric Nephrotic Syndrome

  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.

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