Freely Filtered, a NephJC Podcast

The draft order:Sophia AmbrusoNayan AroraSwapnil HiremathAC GomezJoel TopfEditor Nayan AroraShow NotesPrevious drafts:2021 KDIGO Hypertension —Joel, Sophia, Swap, Nayan, Josh2021 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, Jennie2022 The ISPD Peritonitis Guideline— Joel, Sophia, Swap, Nayan2022 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan2023 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, AC, Josh2024 KDIGO CKD Clinical Practice Guideline —Joel, Sophia, Swap, Nayan, Josh, ACThe guidelineThe NephJC discussion Part 1 | Part 2First RoundSophia’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 WeekThe 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), orheart 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 TangriSecond RoundJoel’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: A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis NEJMTiming of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study NephJCNayan’s Pick Practice Point 1.1.4.2: Use tests to establish a cause based on resources available (Table 6b).Sophia’s Pick Practice Point 1.1.1.2: Following incidental detection of elevated urinary albumin-to-creatinine ratio (ACR), hematuria, or low estimated GFR (eGFR), repeat tests to confirm presence of CKD.Joel’s cystatin C Tweet The cystatin C guideline recommendation 1.1.2.1: In adults at risk for CKD, we recommend using creatinine-based estimated glomerular filtration rate (eGFRcr). If cystatin C is available, the GFR category should be estimated from the combination of creatinine and cystatin C (creatinine and cystatin C– based estimated glomerular filtration rate [eGFRcr-cys]) (1B).Nayan’s additional thoughts. He is not a fan of Practice Points 3.6.4 and 3.6.5Practice Point 3.6.4 Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.andPractice Point 3.6.5: Consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure (estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2).Tubular Secretion Swap The Murderbot Diaries by Martha Wells Nayan Searching for Hobey Baker Narrated by David Duchovny AC Rosie Revere, EngineerSophia BassnectarHow to fix the Apple Music automatically playing when you connect to bluetooth.Joel The Veil with Elizabeth Moss

The Filtrate:Joel TopfJosh WaitzmanWith 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 CarolinaRoger Rodby (@NephRodby) Associate program director of the Rush University Nephrology FellowshipEditor Sophia AmbrusoShow NotesThe manuscript (The Lancet | PubMed | NephJC)The Results of Part A (Kidney Int | PubMed)Edmund (Ed) Louis memorium by Steve Korbet in KISteve Korbet Do not miss this tweet TESTING Freely Filtered #48 with Sean BarbourIptapocan 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 StudyFDA 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 NephJCRepeat 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 kidneyOne 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 TopfSwapnil HiremathJosh WaitzmanNayan AroraSophia AmbrusoWith Special Guest:Brendon Neuen Super smart guy and clinical trialistVlado Perkovic Lead author of FLOW and friend of NephJCEditor Joel TopfShow NotesThe manuscript (NEJM): Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 DiabetesThe 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 BoxBrendon’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: BodkinNephJC Summer Book Club: Covenant of Water by Abraham Verghese (Amazon)

The Filtrate:Joel TopfSwapnil HiremathAC GomezNayan AroraWith Special Guest:Anuja Java, complement god and pre-eclampsia research (Twitter)Shannon M. Clark, MD, FACOG, an honest to god, true, maternal-fetal medicine specialist. (Website | Instagram)Editor Nayan AroraShow NotesCHIP Study from 2015 (NEJM | NephMadness 2015) CHAP study from 2022 (NEJM | NephJC)NephMadness 2024 coverage of the diagnosis of preeclampsia 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)You may just want to listen to Anna Burgner discuss preeclampsia with Kenar Jhaveri and Koyal Jain (GN in Ten) for the NephMadness PodCrawlBene Gesserit (Wikipedia)Pathogenesis of preeclampsia: the genetic component (PubMed)Tubular SecretionsSwap Slow Horses on Apple TV (Wikipedia)AC Hidden Figures (Amazon)Nayan Baseball, little leagueAnuja Young Sheldon (Wikipedia)Joel Dune audiobook (Amazon)

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

Special guest Tim Anderson joins the hosts to discuss inpatient hypertension, focusing on patient outcomes, treatment methods, regional variations, and complexities of hypertension management. They explore challenges in clinical trials, analyzing IV and oral therapies, differentiation between SVT and sinus tachycardia, and navigating complexities in inpatient hypertension management. Book recommendations and discussions on sci-fi series and hiking adventures add a touch of entertainment to the podcast.

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)

Exploring medical research, number needed to treat, deaths of despair, unionization in healthcare, medical fraud, and reflections on an old nephrology textbook's impact. Touching on doctor-patient communication, cognitive biases, and the evolution of medicine. Delving into running marathons, collaboration in healthcare, and the therapeutic value of rest for kidneys.

Podcast covers topics like the impact of balanced crystalloids vs saline in kidney transplants, outcomes of fluid resuscitation trials, autoimmune protocol diet, and Michael Collins (the astronaut). Also, discussions on BEST Fluids, delayed graft function, and Hawthorne Effect.

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)