Episode 69:DUPLEX Sparsentan, it’s no Acthar Gel

The Filtrate:Joel TopfSwapnil HiremathPriya Yenebere Nayan AroraWith Special Guest:Brendon Neuen Super smart guy and clinical trialistMichelle Rheault Lead author of DUPLEX and friend of the podShow NotesSparsentan versus Irbesartan in Focal Segmental GlomerulosclerosisNephJC Summary | PubMed | NEJMKDIGO FSGS Guidelines 2021 (PDF)Characterization of the Clinical Evidence Supporting Repository Corticotropin Injection for FDA-Approved Indications, A Scoping Review (JAMA Internal Medicine)DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS (PubMed)Vlado Perkovic, mentor and sponsor extradenoire (UNSW Sydney)Shimer Its a floor wax and a desert topping (TikTok)SONAR: Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease: a double-blind, randomised, placebo-controlled trial. (NephJC)Travere Therapeutics Announces FDA Accelerated Approval of FILSPARIᵀᴹ (sparsentan), the First and Only Non-immunosuppressive Therapy for the Reduction of Proteinuria in IgA Nephropathy (Travere press release)GFR Slope: Chronic vs Total slope: A meta-analysis of GFR slope as a surrogate endpoint for kidney failure (Nature Medicine)There are dozens of us! Dozens! (Know your Meme)Brendon’s Neuen’s tweet about total versus chronic slope (X | Twitter)Julie R. Ingelfinger, deputy editor for the New England Journal of Medicine (Wikipedia)You know nothing, John Snow (YouTube shorts)Tubular SecretionsSwapnil Foundation season two on Apple TV Wheel of Time season two Amazon PrimeBrendon Andor Priya Poverty, by America Mattew DesmondNayan The Armor of Light: A Novel by Ken FollettMichelle Lessons in Chemistry: A Novel by Bonnie Garmus

The Filtrate:Joel TopfSwapnil HiremathJordy CohenAC GomezWith Special Guest:Tim Anderson @TimAndersonMDEditor:Priya Yenebere Show NotesClinical Outcomes of Intensive Inpatient Blood Pressure Management in Hospitalized Older Adults NephJC Summary | PubMed | JAMA Internal MedicineThe Jordy AC collab: An Interactive Ambulatory Nephrology Curriculum for Internal Medicine Interns: Design, Implementation, and Participant Feedback (PubMed)Clinical Outcomes After Intensifying Antihypertensive Medication Regimens Among Older Adults at Hospital Discharge (PubMed)Trends in Blood Pressure Treatment Intensification in Older Adults With Hypertension in the United States, 2008 to 2018 (PubMed)Overlap Weighting: A Propensity Score Method That Mimics Attributes of a Randomized Clinical Trial (JAMA Guide to Statistics and Methods) Tubular secretionsSwap The Dispatcher by John Scalzi (Wikipedia)AC A Heart that Works by Rob Delaney (NYT Review)Tim Demon Copperhead by Barbara Kingsolver (Amazon)Jordy The Anthropocene Reviewed: Essays on a Human-Centered Planet (Amazon)Joel The Dolomites for hiking n Northern Italy

Animal House RegionNephMadness description by Tiffany TruongEditorial by Kelly Hyndman @DrKeeksPhD They May Look Cute, But Are All Animals Sweet?The Filtrate:Joel TopfSwapnil HiremathSophia AmbrusoJosh WaitzmanWith Special Guest:Kelly HyndmanEditor:Sophia AmbrusoShow NotesAnimal House 2018 with Mark Zeidel, MD (AJKDblog)Animal House 2021 with Kelly Hyndman (AJKDBlog)Animal House 2022 with Kelly Hyndman (AJKDBlog)Mount Desert Island Summer Junket (Website)First person account go a Gila Monster bite (YouTube)Looks like Gila Hank, the gun toting mascot of Eastern Arizona College has been replaced by a non-gun toting Gila monster cowboy. Old logo (Reddit) | New logo (Gila Valley Central Newspaper)Discovery, characterization, and clinical development of the glucagon-like peptides (Drucker JCI 2017)The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease (Rossing NDT 2023)Semaglutide 1.0 mg demonstrates 24% reduction in the risk of kidney disease-related events in people with type 2 diabetes and chronic kidney disease in the FLOW trial (Novo Nordisk)King Gizzard & The Lizard Wizard - Gila Monster (YouTube)Eastern Arizona Campus Store Tubular SecretionsSwap: Three Body Problem (Wikipedia)Josh: Animal Crossing (Nintendo)Sophie: Pyelonephritis in inflammatory bowel disease. Is this a thing?Joel: Maggie Moore(s) (Wikipedia)

How Medicine Works, and When It Doesn’tAmazonThe Filtrate:Joel TopfJosh WaitzmanJennie LinWith Special Guest:Jade TeakellPerry WilsonEditor:Joel TopfShow NotesUnderstanding Medical Research: Your Facebook Friend is Wrong. CourseraIllusory truth effect (Wikipedia)Number needed to treat (Wikipedia)NNT at MedPage Today: NNT on NephJC Deaths of Despair:Suicide (CDC 2001-2021)Drug Overdose (CDC 2001-2021)Steve Jobs delayed therapy for his treatable pancreatic cancer (ABC News)Residents are unionizing at Mass General Brigham. Here's what you need to know (WBUR)Pi and bouncing bricks (YouTube)Doctors in New Zealand—the only non-U.S. country that allows DTC advertising—call for bans (FiercePharma)The Surgisphere Scandal: What Went Wrong? (The Scientist)VITAL SIGNS: FERTILITY; A Study Links Prayer and Pregnancy (The New York Times)Researcher Pulls His Name From Paper on Prayer and Fertility (The New York Times)Tubular SecretionsJosh: Glomerular Nephritis by Thomas Addis (Review in JAMA from 1948)Jennie: The Chicago Marathon Jade: The People’s Hospital (Amazon) Perry: Anathem by Neal Stephenson (Amazon)

The Filtrate:Joel TopfNayan AuroraSophia AmbrusoWith Special Guest:Michael CollinsEditor:Nayan AuroraShow Notes:Twitter is now X (NYT)Michael Collins (the astronaut, not the real one)PlasmaLyte by BaxterNephJC BEST Fluids summaryEarly Goal Directed Therapy for Sepsis NEJM manuscript which changed practice patterns and welcomed in an era of massive fluid resuscitation.PLUS Trial NEJMSPLIT Trial JAMABaSICS NephJC SummarySALTED and SMART NephJC SummaryAdaptive minimization wikipediaBEST Fluids statistical planBEST Fluids in CLinicalTrials.govDelayed Graft Function review in American Journal of TransplantBalanced Crystalloids versus Saline in Critically Ill Adults — A Systematic Review with Meta-Analysis in NEJM EvidenceA pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO) in Kidney InternationalTubular SecretionNayan finally getting around to Succession on HBOSophia autoimmune protocol dietHawthorne EffectMichael Stephen Fry reading Harry Potter

The Filtrate:Joel TopfSwapnil HiremathSophia AmbrusoAC GomezJosh WaitzmanJennie LinNayan AroraThe CurbsidersMatt F. Watto (@DoctorWatto)Paul Nelson Williams, America’s primary care physician (@PaulNWilliamz)With Special Guest:JD Foster (@KidneyVet)Sayed Tabatabai (@TheRealDoctorT) Nephrologist in Austin and the author of These Vital SignsMichelle Rheault (@rheault_m) Chief of Pediatric Nephrology at the University of Minnesota and lead author of the DUPLEX TrialEditor:Joel TopfShow Notes:Lily toxicity in the cat (PubMed)Surgeons perform kidney transplants in cats amid rising demand for advanced pet care (ABC News)Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog (PubMed)Nephrology in Veterinary Medicine (Kidney 360)Star Wars Society of San Antonio (FaceBook)These Vital Signs (Amazon)Dr Tabatabai read a short story called The Handholder, here is the original tweet thread for that story (ThreadReader)The pearl not the patient (PubMed)Late Braking and High Impact Clinical Trial press releaseMENTOR, Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy, was in 2019 not 2017 (NEJM)KALM-1, A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus, was in 2019 not 2017 (NEJM)Sophie’s number one pick: Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial (Lancet)Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058).Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration (AJKD)AC Gomez’s Pick: MDR-101-MLK Update: Operational Immune Tolerance Achieved in Living Related HLA-Matched Kidney Transplant Recipients (ASN-Online.org) Josh’s Pick: A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy (NEJM)Nayan’s Pick: The EnAKT LKD Cluster Randomized Clinical Trial (JAMA Internal Medicine) The Freely Filtered simultaneous release (NephJC)Freely Filtered is now a verb. Swap’s Pick: Strategies for the Management of Atrial Fibrillation in PatiEnts Receiving Dialysis (SAFE-D) (ASN-Online.org)Joel’s Pick: AYAME Study: Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Bardoxolone Methyl in Diabetic Kidney Disease (DKD) Patients (ASN-Online.org)Reata is a no-show to the 2012 ASN Kidney Week (PBFluids)Michelle’s Pick: Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. The DUPLEX Study (NEJM)DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS (PubMed)

The Filtrate:Joel TopfSwapnil HiremathSophia AmbrusoAC GomezWith Special Guest:Amit Garg (@AmitXGarg) Nephrologist at Western University, London, and lead PI of the EnAKT LKD trial. Susan Q. McKenzie (LinkedIn) Co-Founder & Chair, Transplant Ambassador Program. President of the Kidney Patient and Donor Alliance of Canada.Editor:Joel TopfShow Notes:Late Braking and High Impact Clinical Trial press releaseJAMA Internal MedicineMyTEMP trial Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial (PubMed | NephJC | Freely Filtered)Transplant is cheaper! An economic assessment of contemporary kidney transplant practice (PDF)Transplant is better! Survival for waitlisted kidney failure patients receiving transplantation versus remaining on waiting list: systematic review and meta-analysis (PubMed)Transplant disparities Association of Race and Ethnicity With Live Donor Kidney Transplantation in the United States From 1995 to 2014 (PubMed)MUC1 Kidney Disease Autosomal Dominant Tubulointerstitial Kidney Disease: An Emerging Cause of Genetic CKD (Kidney International Reports)This study has all the adjectives: “We conducted a pragmatic, two-arm, parallel-group, open-label, registry-based, superiority, cluster- randomized clinical trial.”Explore Transplant by Amy Waterman, PhDTransplant Ambassador ProgramKidney Failure Risk Equation A Predictive Model for Progression of Chronic Kidney Disease to Kidney Failure (JAMA | Calculator)The complete protocol A Quality Improvement Intervention to Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) in Patients With Chronic Kidney Disease: Clinical Research Protocol of a Cluster-Randomized Clinical Trial (PDF)Pre-published statistical plan Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD): Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial (PubMed)Hawthorne effect (Wikipedia)The Advancing American Kidney Health Initiative “Aim for 80% of new American ESRD patients in 2025 receiving either home dialysis or a transplant” (NKF)Tubular SecretionsSwapnil The Time Travelers Wife by Audrey Niffenegger (Wikipedia) and HBO movie of the same name (Wikipedia).Sophia The Wheel of Time streaming on Amazon (Wikipedia) based on the series of books of the same name by Robert Jordan and Brandon Sanderson.Susan The Woman Who Loved Giraffes movie (Website)Amit Canadians cannot get Visas to visit India (Reuters)AC Eagles are good at Football (Fox Sports) and Alport Connect Meeting in San Diego (Alport Syndrome Foundation Website)Joel Live podcast recording at Kidney Week (NephJC)

The Filtrate:Joel TopfJennie LinJosh WaitzmanWith Special Guest:AC Gomez MedPeds nephrology fellow at Mass General/Brigham and Boston Children’s | TwitterGentian Hall Assistant Professor of Medicine Duke Department of MedicineEditor:Sophia AmbrusoShow Notes:APOL1 review by the OG Scientists APOL1 Nephropathy: From Genetics to Clinical ApplicationsMYH9 and APOL1 connection: The population genetics of chronic kidney disease: insights from the MYH9–APOL1 locusMartin Pollack LabVertex LabWorldwide Frequencies of APOL1 Renal Risk Variants (NEJM)Kidney Disease-Associated APOL1 Variants Have Dose-Dependent, Dominant Toxic Gain-of-FunctionEnd-Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1Apolipoprotein L1 Risk Variants Associate with Systemic Lupus Erythematosus-Associated Collapsing GlomerulopathyHEK293 Cells WikipediaTubular SecretionsJosh: From Serial and the New York Times: The RetrievalsJennie: Marathon induced hyponatremia (NEJM) Donate to the NKF of Illinoise in honor of Jennie’s really long run Donate to New England Donor Services in honor of Josh’s much shorter ruinGentian: Vivien Thomas wikipedia. HBO Movie: Something the Lord MadeAC: Talking to the FDA about SGLT2i TweetJoel: NephJC 2023 Fund drive

Bicarbonate did not slow the loss of GFR in this well done Swiss, single-blind study of transplant patients.The Filtrate:Joel TopfNayan AroraSwapnil HiremathPirya YenebereWith Special Guest:Nav Tangri nephrologist and epidemiology at the University of ManitobaEditor:Nayan AroraShow Notes:Arsenal FCThe London study that kicked it all off!de Brito-Ashurst, I., Varagunam, M., Raftery, M. J., & Yaqoob, M. M. (2009). Bicarbonate supplementation slows progression of CKD and improves nutritional status. Journal of the American Society of Nephrology: JASN, 20(9), 2075–2084.The multi center (but unblinded) UBI Study with mortality benefit!Di Iorio, B. R., Bellasi, A., Raphael, K. L., Santoro, D., Aucella, F., Garofano, L., Ceccarelli, M., Di Lullo, L., Capolongo, G., Di Iorio, M., Guastaferro, P., Capasso, G., & UBI Study Group. (2019). Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study. Journal of Nephrology, 32(6), 989–1001.The BiCARB Study: Double blinded and negativeBiCARB study group. (2020). Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial. BMC Medicine, 18(1), 91.The initial Veverimer StudyWesson, D. E., Mathur, V., Tangri, N., Stasiv, Y., Parsell, D., Li, E., Klaerner, G., & Bushinsky, D. A. (2019). Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. In The Lancet (Vol. 394, Issue 10196, pp. 396–406). doi.org/10.1016/s0140-6736(19)31388-1The Valor CKD trial is still unpublished. But here is the press release. VALOR-CKD design manuscriptThe study of the night: Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomized, single-blind, placebo-controlled, phase 3 trialNephJC | PubMed | LancetAlkali with normal bicarb? Sure, take a look at: Goraya, N., Simoni, J., Jo, C., & Wesson, D. E. (2012). Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney International, 81(1), 86–93.Metforminator!The BASE Trial: Raphael, K. L., Isakova, T., Ix, J. H., Raj, D. S., Wolf, M., Fried, L. F., Gassman, J. J., Kendrick, C., Larive, B., Flessner, M. F., Mendley, S. R., Hostetter, T. H., Block, G. A., Li, P., Middleton, J. P., Sprague, S. M., Wesson, D. E., & Cheung, A. K. (2020). A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial. Journal of the American Society of Nephrology: JASN, 31(1), 161–174.Tubular SecretionsSwap The Three-Body Problem (novel) | NetflixNayan Women’s World CupTangri English Premier Soccer and InflationPriya Silo on Apple TVJoel Live Podcast recording at ASN Kidney

The Filtrate:Joel TopfNayan AroraSophia AmbrusoWith Special Guest:Boback Ziaeian @boback Assistant Professor of Medicine David Geffen School of Medicine at UCLA. His Google Schoolar page is better than yours. And returning for her fourth time (why do we keep inviting her back?)Sadiya Khan @heartDocSadiya Assistant Professor of Medicine (Cardiology) and Preventative Medicine at Northwestern Feinberg School of Medicine. LinkEditor:Priya YenebereShow Notes:Diuretic Therapy review by. Craig Brater NEJMThe manuscript in JAMA | NephJCMetoprolol vs Carvedilol: Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial (Lancet)EMPULSE: The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial (Nature Medicine)Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure The ASTRONAUT Randomized TrialEffects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure The EVEREST Outcome TrialSophia ended up placing fifth in NephMadness 2023. (Link)Joel finished 697thAfter winning in the opening round, Northwestern lost to UCLA, in the second round of the March Madness tournament, 68-63.Torsemide to furosemide equivalents CardioMems positive trial: Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial (The Lancet)CardioMems negative trial: Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial (The Lancet)Estimation of the Absolute Risk of Cardiovascular Disease and Other Events: Issues With the Use of Multiple Fine-Gray Subdistribution Hazard Models (Circulation)Torasemide in chronic heart failure: results of the TORIC study (PubMed)Tubular SecretionsNayan: Louise Penny A World of Curiosities: A Novel (Amazon)Sadiya: Ted Lasso season threeSophia:The Last of Us on HBO and SNL skit Mario Cart as Prestige DramaBoback: Duolingo for Japanese