Freely Filtered, a NephJC Podcast

The FiltrateJoel Topf Bluesky: @kidneyboy.bsky.social‬AC @medpeedskidneys.bsky.social‬Nayan Arora @captainchloride.bsky.social‬Special Guest Vandana Niyyar Professor of Medicine at Emory School of MedicineEditing byNayan AroraThe Kidney Connection written and performed by by Tim YauShow NotesAmerican Society of Diagnostic and Interventional Nephrology (Website)ASDIN List of training sitesPlacement, 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 360Thromboelastogram (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 SecretionsNayan Quarterback on Netflix (Wikipedia)AC The Rehearsal on HBO (Wikipedia)Joel The Detroit Tigers (MLB)

The FiltrateJoel Topf Bluesky: @kidneyboy.bsky.social‬Jordy Cohen Bluesky: @jordybc.bsky.social‬Swapnil Hiremath Bluesky: @hswapnil.medsky.social‬Special Guest Edouard “call me Ed” Fu Assistant Professor and Medical Student, and second author of his second paper covered on NephJC. LinkedIn | Leiden University Medical CenterEditing bySimon Topf and Sophia AmbrusoThe Kidney Connection written and performed by by Tim YauShow NotesEd’s first paper on NephJC: Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study (NephJC | BMJ)Phenformin Wikipedia | Boca Raton NewsThe metformin black box (as part of the FDA Label)WARNING: LACTIC ACIDOSISPostmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see PRECAUTIONS).Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and PRECAUTIONS).If metformin-associated lactic acidosis is suspected, immediately discontinue metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS).Target Trial Emulation A Framework for Causal Inference From Observational Data. Miguel A. Hernán, MD, DrPH; Wei Wang, PhD; David E. Leaf, MD JAMA 2022Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study (NephJC | PubMed)Toxicokinetics of Metformin During Hemodialysis (KI Reports)Metformin in People With Diabetes and Advanced CKD: Should We Dare? Editorial that ran in AJKD along side the Lambourg manuscript (AJKD)Immortal Time Bias in Cohort Studies of Kidney Transplant Recipients (Kim SJ Amer J Trans 2010)Ed’s Target trial review in JASN which Jordy mentioned and includes an explanation of the obesity paradox by depletion of the susceptibles. (Fu JASN 2023)Ed’s Grand Rounds at Ottawa on YouTube. Very good.Response by Cohen et al to Letter Regarding Article, “Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19” by Jordy and the crew Circ Res 2000Review article on the issue: Evaluating sources of bias in observational studies of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use during COVID-19: beyond confounding Jordy and a different crew J Hyperten 2021Figure S5: Weighted cumulative incidence curves for MACE, by treatment strategyThe S4 image that Swap lovedTubular SecretionsJordy Andor Season 2 on Disney+ (Wikipedia)Swapnil Murderbot on Apple TV+ (Wikipedia)Eduoard: New house and grant Grant Grant (Wikipedia)Joel Topf Three Body Problem Audio book (Audible)

The FiltrateJoel TopfAC GomezSophia AmbrusoNayan AroraSpecial Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/HypertensionExtra-Special GuestMichelle Rheault, MD Professor of Pediatrics, University of MinnesotaEditing bySimon and Joel TopfThe Kidney Connection written and performed by by Tim YauShow NotesKDIGO ADPKD Guidelines:WebsiteGuideline PDFExecutive Summary PDFNephJC coverageConsortium 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 normalAnd 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 injuryMeeting 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 first draft pick The bring out your dead pick:Recommendation 4.3.1: We recommend not using mammalian target of rapamycin (mTOR) inhibitors to slow kidney disease progression in people with ADPKD (1C).Recommendation 4.4.1: We suggest not using statins specfiically to slow kidney disease progression in people with ADPKD (2D).Recommendation 4.5.1: We recommend not using metformin specifically to slow the rate of disease progression in people with ADPKD who do not have diabetes (1B).Recommendation 4.6.1: We suggest that somatostatin analogues should not be prescribed for the sole purpose of decreasing eGFR decline in people with ADPKD (2B).Perfect match: mTOR inhibitors and tuberous sclerosis complex (Orphanet Journal of Rare Diseases)Navitor Pharmaceuticals Announces Janssen Has Acquired Anakuria Therapeutics, Inc. (BioSpace) This is press release about acquiring the mTor1 inhibitor.Joel’s second draft pick Recommendation 4.2.1.1: We suggest adapting water intake, spread throughout the day, to achieve at least 2–3 liters of water intake per day in people with ADPKD and an eGFR ≥ 30 ml/min per 1.73 m2 without contraindications to excreting a solute load (2D).Nayan’s bonus draft Practice Point 4.7.1: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) should not be used to slow eGFR decline in people with ADPKD.Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan (KIReports)SMART Trial of GLP-1ra in non-diabetics: Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial (PubMed)Tubular SecretionsNayan: Landman on Paramount Plus (IMDB)Sophia: PassNayan: steps in with The Pitt on HBO (Wikipedia)Charles: The White Lotus, Yellowstone 1923, Poirot (IMDB)AC: The PittMichael Crichton’s Estate Sends The Pitt to the Courtroom (Vulture)Joel: I Must Betray you by Ruta Sepetys (Amazon)

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)

The FiltrateJoel TopfJordy CohenNayan AroraSpecial Guest Katie Kwon @katiekwonmd.bsky.socialMariana Murea @MarianaMureaEditing bySimon Topf and Joel TopfShow NotesNephMadness at AJKDblog.orgThe Hemodialysis RegionVote for your favorites

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

The Filtrate:Joel TopfSwapnil HiremathWith Special Guest:Michelle Hladunewich, Nephrologist at the University of TorontoMir Melamed, Maternal-Fetal Medicine at the University of TorontoEditor Simon TopfShow NotesPriscilla 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 entertainmentTim Yau (@Maximal_Change)Too Sweet by HozierFairy Tale of New York by written Jem Finer and Shane MacGowan. Hear it performed by the Pogues.Interview of Tom MuellerTom Mueller author of How to Make a KillingJade Teakall@jmteakellGraham Abra@GrahamAbraInterview of Tom MuellerTom Mueller author of How to Make a KillingJade Teakall @jmteakellGraham Abra @GrahamAbraNephMadness logo revealNephJC KidneysNephJC blog postNephJC Manuscript of the Year: Flow accepted by Meg JardineManjula 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 logoNephJC Social Justice Award: ISN petition to the WHO on Kidney HealthMost Engaged Scientist Award: Michelle RheaultRookie of the Year: Milagros FloresMVP: Christina PopaNephJC Founders Award: Joshua WaitzmanNathan Hellman Social Media Project of the Year: Edgar Lerma and the ASN Visual Abstract TeamMore Music with TimSaginaw, Michigan as performed by Johny CashBetty, written by Taylor SwiftThe Kidney ConnectionFreely Filtered Kidney Week DraftPrevious drafts2021 ASN Kidney Week Draft2022 ASN Kidney Week Draft2023 ASN Kidney Week DraftList of all the simultaneous publications from Kidney Week 2024Sophia: SMART Trial (Link goes to the new KidneyCompass podcast that interview lead author Hiddo HeerspinkJordy’s editorial in the European Heart Journal. LinkJosh: APPLAUSE Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy in the NEJMAPPLAUSE results announcement at The World Congress of Neophrology in Buenos AriesIptapocan is a factor B inhibitionJordy: POISE-3 with simultaneous publication in KIMentions she wanted to pick KAT-AKI because she worked with Perry Wilson.Per Nayan, Amit Garg is the Beyonce of NephrologyAccord Trial (NEJM)Joel: HSK21541 for PruritusCorrection link to source (graph)Nayan: FINEARTS-HF with simultaneous publication in JACCBARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine)Swapnil comes out as a SpiroStanTOPCAT funny businessPATHWAY-2 Trial (NephJC coverage)Swap: K Bath and cardiac arrhythmia with simultaneous publication in Kidney InternationalCAST: A study that rocked the cardiology world and became the poster child for evidence-based medicine (Link)Tubular SecretionsSwap: Late breaking and high impact sessionsNayan: Intro to…Joel: Student poster on blood pressure techniqueJordy: The Penguin. A couple of mentee postersSophie: Tracks her sessions on paper.Josh: Quiz and Questionaire session with JC Velez, Bea Concepcione, Anna Burgner, Roger Rodby.

The Filtrate:Jennie LinJoel TopfJosh WaitzmanSwapnil HiremathWith Special GuestsPedro TeixeiraJay KoynerEditor Sophia AmbrusoShow NotesThe article: A Randomized Trial of Intravenous Amino Acids for Kidney ProtectionNephJC SummaryKDIGO 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 SecretionsSwapnil 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 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

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)