Freely Filtered, a NephJC Podcast

The Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ (COI) Sophia Ambruso @sophia-kidney.bsky.social Swapnil Hiremath @hswapnil.medsky.social and on LinkedIn Special Guests Jonathan Barratt Professor of Renal Medicine, University of Leicester Google Scholar (COI: all the companies) Editing and Show Notes by Nayan Arora @captainchloride.bsky.social The Kidney Connection written and performed by Tim Yau Show Notes Proteinuria 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 Secretion Swapnil Hiremath Pluribus on Apple TV (Wikipedia) Jon Barratt Lynyrd Skynyrd (Wikipedia) Slow Horses (Wikipedia) on AppleTV Joel Topf the new ASN

The Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ (COI) Pedro Teixeira @nephcrit.bsky.social Ana Gaddy @AnnaGaddy Nayan Arora @captainchloride.bsky.social Special Guests David Goldfarb Professor of Medicene, NYU (COI) Editing by Pedro Teixeira The Kidney Connection written and performed by Tim Yau Show Notes BICARBICU 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 Secretions Nayan: 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 Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ (COI) Swapnil Hiremath @hswapnil.medsky.social and on LinkedIn Pedro Teixeira @nephcrit.bsky.social Special Guests Charmaine E Lok, MD Professor of Medicine at the Faculty of Medicine, University of Toronto Editing and Show Notes by Joel Topf The Kidney Connection written and performed by Tim Yau Show Notes Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis NEJM | NephJC What works in hemodialysis? Iron: PIVOTAL Trial (NEJM) Hemodiafiltration: CONVINCE (NEJM) That’s the whole list Earlier 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 JAMA Eskimo 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-IT Negative trial of fish oil in non-dialysis patients: STRENGTH ACC 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 Secretions Swapnil 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 Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ (COI) Sophia Ambruso @sophia-kidney.bsky.social Swapnil Hiremath @hswapnil.medsky.social and on LinkedIn Special Guests Jonathan Barratt Professor of Renal Medicine, University of Leicester Google Scholar (COI: all the companies) Editing and Show Notes by Nayan Arora @captainchloride.bsky.social The Kidney Connection written and performed by Tim Yau Show Notes Proteinuria 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 Secretion Swapnil Hiremath Pluribus on Apple TV (Wikipedia) Jon Barratt Lynyrd Skynyrd (Wikipedia) Slow Horses (Wikipedia) on AppleTV Joel Topf the new ASN

The Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ Sophia Ambruso @sophia-kidney.bsky.social Nayan Arora @captainchloride.bsky.social Special Guests Brian Rifkin @brianrifkin.bsky.social Anna Gaddy @AnnaGaddy Editing and Show Notes by Joel Topf The Kidney Connection written and performed by Tim Yau Show Notes Brian 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 Secretion Brian: Late Breaking and High Impact Clinical Trials. Including Sibe! REGENCY Biopsy Data. Sophia: Flying Home. No, really it’s the Electrolyte Quiz Joel: The Poster Session, the Quiz Session, and Nayan: Flying to AHA to talk about dual-heart-kidney-transplant Anna: Kidney STARS! and Melanie Hoenig’s session on potassium

The Filtrate Joel Topf‍ ‍@kidneyboy.bsky.social‬ Swapnil Hiremath@hswapnil.medsky.social AC @medpeedskidneys.bsky.social Special Guest Mike 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 by Sophia Ambruso The Kidney Connection written and performed by Tim Yau Show Notes ALCHEMIST (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 hypothesis Swap 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 secretions Swap is probably stalking Martha Wells by now, has moved on from Witch King, now onto Queen Demon on Good Reads AC is adding to her brood, 2 dogs (Snickers & Harper), 1 child Dungeon 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 Filtrate Joel Topf @kidneyboy.bsky.social‬ Swapnil Hiremath @hswapnil.medsky.social Nayan Arora captainchloride.bsky.social Sopia Ambruso @sophia-kidney.bsky.social Special 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 Semaglutide Muthiah Vaduganathan @mvaduganathan on X. Cardiologist at Brigham and Women's Hospital and Harvard Medical School. Assistant Professor of Medicine. Editing by Joel Topf The Kidney Connection written and performed by Tim Yau Show Notes DONATE to NephJC! Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes NEJM | NephJC Summary FIDELIO Bakris et al, NEJM 2020 | NephJC Summary; subgroup throws doubt on efficacy of finerenone in patients on flozins FIGARO Pitt et al, NEJM 2021; subgroups clearly shows finerenone works, flozins or not NEJM 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 2013 Why 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 Secretions Nayan 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 Filtrate Joel Topf Bluesky: @kidneyboy.bsky.social‬ AC @medpeedskidneys.bsky.social‬ Nayan Arora @captainchloride.bsky.social‬ Special Guest Vandana Niyyar Professor of Medicine at Emory School of Medicine Editing by Nayan Arora The Kidney Connection written and performed by by Tim Yau Show Notes American Society of Diagnostic and Interventional Nephrology (Website) ASDIN List of training sites Placement, 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 360 Thromboelastogram (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 Secretions Nayan Quarterback on Netflix (Wikipedia) AC The Rehearsal on HBO (Wikipedia) Joel The Detroit Tigers (MLB)

The Filtrate Joel Topf Bluesky: @kidneyboy.bsky.social‬ Jordy Cohen Bluesky: @jordybc.bsky.social‬ Swapnil Hiremath Bluesky: @hswapnil.medsky.social‬ Special 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 Center Editing by Simon Topf and Sophia Ambruso The Kidney Connection written and performed by by Tim Yau Show Notes Ed’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 News The metformin black box (as part of the FDA Label) WARNING: LACTIC ACIDOSIS Postmarketing 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 2022 Stopping 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 2000 Review 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 2021 Figure S5: Weighted cumulative incidence curves for MACE, by treatment strategy The S4 image that Swap loved Tubular Secretions Jordy 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 Filtrate Joel Topf AC Gomez Sophia Ambruso Nayan Arora Special Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/Hypertension Extra-Special Guest Michelle Rheault, MD Professor of Pediatrics, University of Minnesota Editing by Simon and Joel Topf The Kidney Connection written and performed by by Tim Yau Show Notes KDIGO ADPKD Guidelines: Website Guideline PDF Executive Summary PDF NephJC coverage Consortium 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 normal And 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 injury Meeting 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...

The Filtered Fragments (OG Filtrate) Joel Topf Jennie Lin Swapnil Hiremath Special Guest Brad Rovin GN God and second author from The Ohio State Koyal Jain GN Specialist from UNC Alfred Kim 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 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 REGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM | NephJC NOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic Disease Comparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed Central 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 Tubular Secretions Swap: 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 Say Al: Acquired Podcast Brad: The Feather Thief by Kirk Wallace Johnson (Amazon) Joel: Paradise on Hulu (Wikipedia)

The Filtrate Joel Topf Jordy Cohen Nayan Arora Special Guest Katie Kwon @katiekwonmd.bsky.social Mariana Murea @MarianaMurea Editing by Simon Topf and Joel Topf Show Notes NephMadness at AJKDblog.org The Hemodialysis Region Vote for your favorites

The Filtrate Joel Topf Swapnil Hiremath AC Gomez Sopia Ambruso Nayan Arora Special Guests Michelle Rheault, Director, Division of Pediatric Nephrology, Professor of Medicine 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 FINEARTS Kidney outcomes in JACC FINE-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 KidneyWk Swapnil comes out as a SpiroStan post to NephJC TOPCAT TOPCAT primary publication TOPCAT North American results TOPCAT funny business explained AHA/ACC/HFSA Heart Failure Guidelines (PDF) 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 Kansas 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.2635 Why Has it Been Challenging to Modify Kidney Disease Progression in Patients With Heart Failure? (JACC) Tubular Secretions Swap: Disclaimer on Apple TV AC: Duo Lingo Plushy (Amazon) Nayan: The Puzzle Box Jordy: Project Hail Mary Brendon 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 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) 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 entertainment Tim Yau (@Maximal_Change) Too Sweet by Hozier Fairy Tale of New York by written Jem Finer and Shane MacGowan. Hear it performed by the Pogues. Interview of Tom Mueller Tom Mueller author of How to Make a Killing Jade Teakall@jmteakell Graham Abra@GrahamAbra Interview of Tom Mueller Tom Mueller author of How to Make a Killing Jade Teakall @jmteakell Graham Abra @GrahamAbra NephMadness logo reveal NephJC Kidneys NephJC blog post NephJC Manuscript of the Year: Flow accepted by Meg Jardine Manjula 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 logo NephJC Social Justice Award: ISN petition to the WHO on Kidney Health Most Engaged Scientist Award: Michelle Rheault Rookie of the Year: Milagros Flores MVP: Christina Popa NephJC Founders Award: Joshua Waitzman Nathan Hellman Social Media Project of the Year: Edgar Lerma and the ASN Visual Abstract Team More Music with Tim Saginaw, Michigan as performed by Johny Cash Betty, written by Taylor Swift The Kidney Connection Freely Filtered Kidney Week Draft Previous drafts 2021 ASN Kidney Week Draft 2022 ASN Kidney Week Draft 2023 ASN Kidney Week Draft List of all the simultaneous publications from Kidney Week 2024 Sophia: SMART Trial (Link goes to the new KidneyCompass podcast that interview lead author Hiddo Heerspink Jordy’s editorial in the European Heart Journal. Link Josh: APPLAUSE Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy in the NEJM APPLAUSE results announcement at The World Congress of Neophrology in Buenos Aries Iptapocan is a factor B inhibition Jordy: POISE-3 with simultaneous publication in KI Mentions she wanted to pick KAT-AKI because she worked with Perry Wilson. Per Nayan, Amit Garg is the Beyonce of Nephrology Accord Trial (NEJM) Joel: HSK21541 for Pruritus Correction link to source (graph) Nayan: FINEARTS-HF with simultaneous publication in JACC BARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine) Swapnil comes out as a SpiroStan TOPCAT funny business PATHWAY-2 Trial (NephJC coverage) Swap: K Bath and cardiac arrhythmia with simultaneous publication in Kidney International CAST: A study that rocked the cardiology world and became the poster child for evidence-based medicine (Link) Tubular Secretions Swap: Late breaking and high impact sessions Nayan: Intro to… Joel: Student poster on blood pressure technique Jordy: The Penguin. A couple of mentee posters Sophie: Tracks her sessions on paper. Josh: Quiz and Questionaire session with JC Velez, Bea Concepcione, Anna Burgner, Roger Rodby.

The Filtrate: Jennie Lin Joel Topf Josh Waitzman Swapnil Hiremath With Special Guests Pedro Teixeira Jay Koyner Editor Sophia Ambruso Show Notes The article: A Randomized Trial of Intravenous Amino Acids for Kidney Protection NephJC Summary KDIGO 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 Secretions Swapnil 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)

The draft order: Sophia Ambruso Nayan Arora Swapnil Hiremath AC Gomez Joel Topf Editor Nayan Arora Show Notes Previous drafts: 2021 KDIGO Hypertension —Joel, Sophia, Swap, Nayan, Josh 2021 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, Jennie 2022 The ISPD Peritonitis Guideline— Joel, Sophia, Swap, Nayan 2022 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan 2023 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, AC, Josh 2024 KDIGO CKD Clinical Practice Guideline —Joel, Sophia, Swap, Nayan, Josh, AC The guideline The NephJC discussion Part 1 | Part 2 First Round Sophia’s Pick 3.7.1 We recommend treating patients with type 2 diabetes (T2D), CKD, and an eGFR ≥20 ml/min per 1.73 m2 with an SGLT2i (1A). Not Nayan’s Pick 3.7.3: We suggest treating adults with eGFR 20 to 45 ml/min per 1.73 m2 with urine ACR <200 mg/g (<20 mg/mmol) with an SGLT2i (2B). Nayan’s Pick 2.2.1: In people with CKD G3–G5, we recommend using an externally validated risk equation to estimate the absolute risk of kidney failure (1A). A birdie told me there will not be a Tangri KFRE vs the World debate at Kidney Week The action points based on absolute risk results: Practice Point 2.2.1: A 5-year kidney failure risk of 3%–5% can be used to determine need for nephrology referral in addition to criteria based on eGFR or urine ACR, and other clinical considerations. Practice Point 2.2.2: A 2-year kidney failure risk of >10% can be used to determine the timing of multidisciplinary care in addition to eGFR-based criteria and other clinical considerations. Practice Point 2.2.3: A 2-year kidney failure risk threshold of >40% can be used to determine the modality education, timing of preparation for kidney replacement therapy (KRT) including vascular access planning or referral for transplantation, in addition to eGFR-based criteria and other clinical considerations. Swap’s Pick 3.15.1.1: In adults aged ‡50 years with eGFR <60 ml/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation (GFR categories G3a–G5), we recommend treatment with a statin or statin/ezetimibe combination (1A). AC’s Pick 3.7.2: We recommend treating adults with CKD with an SGLT2i for the following (1A): eGFR ≥20 ml/min per 1.73 m2 with urine ACR ≥200 mg/g (≥20 mg/mmol), or heart failure, irrespective of level of albuminuria. (1A) Joel’s Pick 3.10.1: In people with CKD, consider use of pharmacological treatment with or without dietary intervention to prevent development of acidosis with potential clinical implications (e.g., serum bicarbonate <18 mmol/l in adults). Practice Point 3.10.2: Monitor treatment for metabolic acidosis to ensure it does not result in serum bicarbonate concentrations exceeding the upper limit of normal and does not adversely affect BP control, serum potassium, or fluid status. Freely Filtered 061: Bicarb in Transplant with Nav Tangri Second Round Joel’s Pick 3.3.1.1: We suggest maintaining a protein intake of 0.8 g/kg body weight/d in adults with CKD G3–G5 (2C). Practice points related to protein intake: 3.3.1.1: Avoid high protein intake (>1.3 g/kg body weight/d) in adults with CKD at risk of progression. 3.3.1.2: In adults with CKD who are willing and able, and who are at risk of kidney failure, consider prescribing, under close supervision, a very low–protein diet (0.3–0.4 g/kg body weight/d) supplemented with essential amino acids or ketoacid analogs (up to 0.6 g/kg body weight/d). 3.3.1.3: Do not prescribe low- or very low–protein diets in metabolically unstable people with CKD. AC’s Pick 3.9.1: In adults with T2D and CKD who have not achieved individualized glycemic targets despite use of metformin and SGLT2 inhibitor treatment, or who are unable to use those medications, we recommend a long-acting GLP-1 RA (1B). Swapnil’s Pick Practice Point 5.4.1: Initiate dialysis based on a composite assessment of a person’s symptoms, signs, QoL, preferences, level of GFR, and laboratory abnormalities. IDEAL Trial:...

The Filtrate: Joel Topf Josh Waitzman With Special Guest: Brad Rovin (@BradRovin) Chief of nephrology at The Ohio State University Wexner Medical Center, one of the authors of the Nefigard trial. Koyal Jain (@koyaljainMD) Program director of the GN Fellowship at University of North Carolina Roger Rodby (@NephRodby) Associate program director of the Rush University Nephrology Fellowship Editor Sophia Ambruso Show Notes The manuscript (The Lancet | PubMed | NephJC) The Results of Part A (Kidney Int | PubMed) Edmund (Ed) Louis memorium by Steve Korbet in KI Steve Korbet Do not miss this tweet TESTING Freely Filtered #48 with Sean Barbour Iptapocan at the World Congress of Nephrology: WCN24-1506 Efficacy And Safety Of Iptacopan In Patients With IgA Nephropathy: Interim Results From The Phase 3 APPLAUSE-IgAN Study FDA and mandatory post-marketing studies. What happens when the study is negative (or not completed) (UNDARK) Who should treat lupus nephritis: rheumatologists or nephrologists? (Nature Reviews Nephrology) Protein and albumin-to-creatinine ratios in random urines accurately predict 24 h protein and albumin loss in patients with kidney disease (PubMed) MEST Scores in NephJC Risk scores in IgAN in NephJC Repeat renal biopsy improves the Oxford classification-based prediction of immunoglobulin A nephropathy outcome (NDT) Tarpeyo pills 4 mg. Four pills once a day. (WellRx has a picture of the pills) IgA nephropathy in African Americans: uncommon but possible (PubMed Central) Aberrantly Glycosylated IgA1 in IgA Nephropathy: What We Know and What We Don’t Know (PubMed Central) Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy (JAMA Network Open) Tubular Secretions Joel: Constellation on Apple TV (Wikipedia). Not good. Dune audio books are excellent. (Audible) Josh: Podcasts about donating a kidney One Is Enough Podcast (National Kidney Registry) Donor Diaries (National Kidney Donation Organization) Roger Iceland (Wikipedia) Koyal India (Wikipedia) Brad Fishing in Dubai

The Filtrate: Joel Topf Swapnil Hiremath Josh Waitzman Nayan Arora Sophia Ambruso With Special Guest: Brendon Neuen Super smart guy and clinical trialist Vlado Perkovic Lead author of FLOW and friend of NephJC Editor Joel Topf Show Notes The manuscript (NEJM): Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes The acronym FLOW from the title: evaluate renal Function with semagLutide Once Weekly (Twitter) Joel wrote a blog post prior to the FLOW publication to try to set the table: Peeking Inside Schrödinger’s Box Brendon’s Neuen’s tweet about total versus chronic slope (X | Twitter) Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity (Science Direct) Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials (PubMed) The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis (Frontiers in Pharmacology) Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials (PubMed) Proteinuria Thresholds Are Irrational: A Call for Proteinuria Indexing (Nephron Clinical Practice) Frank Harrel on why the NNT sucks (data methods) Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells (PubMed) Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance (PubMed) Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial (PubMed) Doctors are like the pyromaniac fireman (PBFluids) Suggest topics for NephMadness (Twitter) Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE) (PubMed) Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial (PubMed) Spitzer’s involvement in revolutionizing nephrology is part of this lecture I did at the University of Nebraska Diabetes Symposium. (Dropbox: Start on slide 29) Spitzer Resigns, Citing Personal Failings (New York Times) Tubular Secretions Swap: Dumb Money on NetFlix (Wikipedia) Josh: Hiking Zion National Park (National Park Service) Sophia: Lost in Space 2018 TV series on NetFlix (Wikipedia) Nayan: Pelican Hill resort (Website) Joel: Bodkin NephJC Summer Book Club: Covenant of Water by Abraham Verghese (Amazon)