Freely Filtered, a NephJC Podcast

The Filtered Fragments (OG Filtrate)Joel TopfJennie LinSwapnil HiremathSpecial Guest Brad Rovin GN God and second author from The Ohio StateKoyal Jain GN Specialist from UNCAlfred Kim Rheumatologist from Washington UniversityEditing bySimon Topf and Nayan AroraThe Kidney Connection written and performed by by Tim YauShow NotesJoel’s monologue One of the most surprising facts of nephrology is that despite conventional wisdom that lupus nephritis is an antibody mediated disease, that over a decade ago, the LUNAR investigtors were unable to find a significant benefit when rituximab was added to conventional therapy. And this was after the equally negative phase 2 trial of rituximab, EXPLORER.In fact, despite this finding rituximab has been able to burough its way into treatment of many nephrologists and rheumatologists as well as the KDIGO guidelines where it is suggested for patients with persistent disease activity or inadequate response to initial standard-of-care therapy.This long conflict is now coming to an end. Obinutuzumab, a newer, better monoclonal antibody targeting the same CD20 that we grew to love with rituximab, but it has a number of advantages.One. It is humanized antibody rather than a chimeric mouse-human antibodyTwo. It’s cytotoxicity is not complement dependent an particular advantage if you want to deploy it ina disease where hypocomplementemia is a disease characteristicThree, and most importantly, it causes stronger and deeper b-cell depletion than rituximab. Better B-cell depletion in the blood and tissue.And this brings us to tonight’s topic, we had already seen the phase two results of obinutuzumab which, unlike EXPLORER, were positive, we will look at the phase three  regency trial. This makes the third novel lupus nephritis drug in the last 4 years. We continue to remake glomerular nephritis.LUNAR: Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study PubmedEXPLORER: Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial PubmedREGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM | NephJCNOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic DiseaseComparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed CentralClass 5 lupus nephritis is slow to respond Long-term Use of Voclosporin in Patients with Class V Lupus Nephritis: Results from the AURORA 2 Continuation Study ACR Meeting abstractTubular SecretionsSwap: Young Adult novel I Must Betray You by Ruta Sepetys (Amazon)Koyal: Taekwondo (Wikipedia)Jennie: these unprecedented times Trump NYT: Administration Freezes $1 Billion for Cornell and $790 Million for Northwestern, Officials SayAl: Acquired PodcastBrad: The Feather Thief by Kirk Wallace Johnson (Amazon)Joel: Paradise on Hulu (Wikipedia)

Join nephrologists Nayan Arora, Jordy Cohen, Katie Kwon, and Mariana Murea as they dive into the latest innovations in dialysis. They discuss the Neff Madness bracket, highlighting breakthroughs in hemodialysis and hemodiafiltration technology. The conversation covers patient-centered care strategies, molecular clearance, and sustainability in dialysis resources. Each guest brings unique insights into the complexities of managing kidney health, balancing humor with serious discussions about improving patient outcomes in the evolving world of nephrology.

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

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

Mir Melamed, a maternal-fetal medicine expert at the University of Toronto, dives deep into the complexities of preeclampsia. He discusses the collaborative care model uniting nephrology and maternal-fetal specialists to support high-risk pregnancies. The conversation highlights critical biomarkers like S-Fleet and PLGF that aid in diagnosis and management. Melamed also emphasizes the importance of individualized care for renal disease patients, shedding light on the intricate balance of management during pregnancy. Insights into hypertension management and the clinical applications of diagnostic tools are also shared.

Tim Yau, a nephrologist and musical talent, shares his unique blend of music and nephrology. Tom Mueller, author of "How to Make a Killing," discusses the ethical dilemmas in the dialysis industry, shedding light on the struggle between corporate interests and patient care. Graham Abra and Jade Teakall explore the importance of home therapies and the upcoming NephMadness event. They celebrate nephrology achievements with awards, emphasizing social justice and community engagement while enjoying lighthearted musical interludes.

In this engaging discussion, Nephrologists Pedro Teixeira, an expert in clinical trials from the University of New Mexico, and Jay Koyner from the University of Chicago dive into the intriguing role of amino acids in managing acute kidney injury (AKI). They unpack recent clinical trials and explore the complexities of kidney function assessments. The conversation also touches on the relationship between amino acids and renal functional reserve, and the comparison with SGLT2 inhibitors in AKI prevention. Expect insightful analysis and practical implications for patient care!

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)