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FF 80 KDIGO ADPKD Guideline Draft

The Filtrate Joel Topf AC Gomez Sophia Ambruso Nayan Arora Special Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/Hypertension Extra-Special Guest Michelle Rheault, MD Professor of Pediatrics, University of Minnesota Editing by Simon and Joel Topf The Kidney Connection written and performed by by Tim Yau Show Notes KDIGO ADPKD Guidelines: Website Guideline PDF Executive Summary PDF NephJC coverage Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) Hy’s Law (Wikipedia) has three components: ALT or AST by 3-fold or greater above the upper limit of normal And total serum bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal) And no other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injury Meeting this definition yields a very high risk of fulminant kidney failure (76% in one series) Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database (PubMed) Two of 957 patients on tolvaptan met Hy’s law criteria. None had fulminant kidney failure. Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial (PubMed) Patients had a baseline urine volume on tolvaptan of 6.9 L/24 h. Urine volume decreased to 5.1 L/24 h with hydrochlorothiazide and to 5.4 L/24 h on metformin. TEMPO 3:4 Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease (NEJM) Reprise Trial Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease ( NEJM | NephJC ) Unified ultrasonographic diagnostic criteria for polycystic kidney disease by Edelstein in JASN (PubMed) Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies (PubMed) Charles’ draft choice Recommendation 4.1.1.1: We recommend initiating tolvaptan treatment in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ‡25 ml/min per 1.73 m2 who are at risk for rapidly progressive disease (1B). Sophia’s draft choice Recommendation 1.4.2.1: We recommend employing the Mayo Imaging Classi cation (MIC) to predict future decline in kidney function and the timing of kidney failure (1B). Progression to kidney failure in ADPKD: the PROPKD score underestimates the risk assessed by the Mayo imaging classification (Frontiers of Science) AC’s draft choice Recommendation 9.2.1: We recommend targeting BP to ≤ 50th percentile for age, sex, and height or ≤ 110/70 mm Hg in adolescents in the setting of ADPKD and high BP (1D). HALT-PKD Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease (NEJM) Nayan’s draft choice Recommendation 6.1.2: We recommend screening for ICA in people with ADPKD and a personal history of SAH or a positive family history of ICA, SAH, or unexplained sudden death in those eligible for treatment and who have a reasonable life expectancy (1D). Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease (CJASN) Surgical Clipping Versus Endovascular Coiling in the Management of Intracranial Aneurysms (PubMed) Clipping is associated with a higher rate of occlusion of the aneurysm and lower rates of residual and recurrent aneurysms, whereas coiling is associated with lower morbidity and mortality and a better postoperative course. Joel’s editorial pick Recommendation 6.1.1: We recommend informing adults with ADPKD about the increased risk for intracranial aneurysms (ICAs) and subarachnoid hemorrhage (1C). Joel’s 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 Secretions Nayan: Landman on Paramount Plus (IMDB) Sophia: Pass Nayan: steps in with The Pitt on HBO (Wikipedia) Charles: The White Lotus, Yellowstone 1923, Poirot (IMDB) AC: The Pitt Michael Crichton’s Estate Sends The Pitt to the Courtroom (Vulture) Joel: I Must Betray you by Ruta Sepetys (Amazon)

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Freely Filtered 002

This week we discussed the ASCEND trial published in Annals of Internal Medicine, on the comparative effectiveness of cognitive behavioural therapy and Sertraline in patients on dialysis with depression. The article is available here. The NephJC summary can be read here, with links to the visual abstract. Links from the show: In the background section, we mentioned the data from a recent JASN study on cardiovascular safety of different antidepressants. The contrast with the CAST trial came up as well. PDF links to the BDI, QIDS-SR and QIDS-C scores. KIDNEYCon 2020 will be in April. Follow @KIDNEYCon to stay updated, as well for the links to the recorded sessions from #KIDNEYCon 2019. Host: Joel Topf Discussants: Swapnil Hiremath, Jennie Lin and Matt Sparks. We missed Samira Farouk who was travelling.

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Freely Filtered 065: BEST Fluids

The Filtrate: Joel Topf Nayan Aurora Sophia Ambruso With Special Guest: Michael Collins Editor: Nayan Aurora Show Notes: Twitter is now X (NYT) Michael Collins (the astronaut, not the real one) PlasmaLyte by Baxter NephJC BEST Fluids summary Early Goal Directed Therapy for Sepsis NEJM manuscript which changed practice patterns and welcomed in an era of massive fluid resuscitation. PLUS Trial NEJM SPLIT Trial JAMA BaSICS NephJC Summary SALTED and SMART NephJC Summary Adaptive minimization wikipedia BEST Fluids statistical plan BEST Fluids in CLinicalTrials.gov Delayed Graft Function review in American Journal of Transplant Balanced Crystalloids versus Saline in Critically Ill Adults — A Systematic Review with Meta-Analysis in NEJM Evidence A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO) in Kidney International Tubular Secretion Nayan finally getting around to Succession on HBO Sophia autoimmune protocol diet Hawthorne Effect Michael Stephen Fry reading Harry Potter

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FF 70b Do Over: The PRAECIS trial, predicting severe preeclampsia

The Filtrate: Joel Topf Swapnil Hiremath With Special Guest: Michelle Hladunewich, Nephrologist at the University of Toronto Mir Melamed, Maternal-Fetal Medicine at the University of Toronto Editor Simon Topf Show Notes Priscilla Smith’s letter: Dear Joel and the Freely Filtered team, I am a long-time fan of your podcast and was looking forward to hearing your recently aired discussion of the Praecis study of sflt1:PlGF use in preeclampsia. Preeclampsia and renal disease in pregnancy are areas that many nephrologists report a lack of knowledge or confidence in discussing and managing. I am a nephrologist who has been co-leading a renal pregnancy clinic in London while writing a PhD on progression of renal disease in pregnancy. I have had the immense privilege of working with experts and key opinion leaders in preeclampsia research both in the UK and internationally. As you know, preeclampsia is a serious and significant condition contributing to global maternal mortality and is also associated with future CKD and CVD risk so is both relevant and important within our professional group. Sadly, I found myself disappointed by the episode and felt it was a missed opportunity. I appreciate that you had difficulties obtaining appropriate experts to join the discussion, but perhaps it would have been better to delay production. While you all valiantly proceeded to discuss this important study, the topic is complex and there appeared to be a lack of understanding of the surrounding literature and pathogenesis of preeclampsia. Sadly, the maternal medicine expert’s comments at the end of the podcast added little as she seemed determine to negate any benefit from the results despite declaring she had no experience or expertise in the use of these biomarkers. There are many people who understand the clinical aspects of preeclampsia as well as having direct experience of the use and utility of these biomarkers who would have been able to contribute much to your conversation. I look forward to future discussions of renal disease in pregnancy on your podcast and would be happy to suggest some expert panellists if you ever find yourself stuck. Kind regards, Priscilla Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia (JCI 2003) sFlt background: Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta (PubMed) PlGF background: Perspectives on the Use of Placental Growth Factor (PlGF) in the Prediction and Diagnosis of Pre-Eclampsia: Recent Insights and Future Steps (PubMed) The PRAECIS trial (NephJC | NEJM Evidence)

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Allopurinol Fixes the Numbers and Little Else

The Filtrate: Joel Topf Swapnil Hiremath Samira Farouk And special guests: Katalin Susztak, Professor of Medicine Perlman School of Medicine, University of Pennsylvania. @KSusztak Show Notes: CKD-FIX: Effects of Allopurinol on the Progression of Chronic Kidney Disease PERL: Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes Coverage at NephJC: Effects of Allopurinol on the Progression of Chronic Kidney Disease Richard Johnson’s theory in pay-walled Nature Reviews Nephrology: Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome Richard Johnson’s theory in open access Nehrology Dialysis and Transplantation: Uric acid and chronic kidney disease: which is chasing which? PERL: Preventing early renal loss Iohexol, good for measuring GFR as well as causing contrast associated nephropathy? Uric acid versus urate: The Crystallization of Monosodium Urate Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis WHO list of essential medications Fixing the numbers, specifically phosphorous GFR Decline as an End Point for Clinical Trials in CKD: A Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration Cost of allopurinol: $7/month but it is only $9 for 3 months Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial Tipping point analysis - multiple imputation for stress test under missing not at random (MNAR) or a YouTube video if that’s your speed (sorry, I couldn’t find a TikTok on imputation stress tests). Mendelian randomization study of urate and CKD by Ron Do and team Dad jokes Fake systematic review by Johnson’s group showing Urate lowering prevented CKD Hyperuricemia As a trigger of Immune Response in Hypertension and Chronic Kidney Disease by Claudio Ponticelli published the week after these two RCTs were published. NEJM Editorial: Urate-Lowering Therapy and Chronic Kidney Disease Progression by Daniel Feig COVID and PPI manuscript Hashtag the cowboy ‘WhatsApp®’ening in nephrology training Arkana LIVE Pathology Sessions NephJC Summer Book Club. Read Rana Awdish’s In Shock

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Freely Filtered 50: CLASSIC Trial

The Filtrate: Joel Topf Swapnil Hiremath Jennie Lin Special Guests: Priya Yenebere @PriRenalAKI Transplant nephrologist at Indiana University School of Medicine. She is a current NSMC Intern. J Pedro Teixeira @NephCrit_NM ICU Nephrologist at the University of New Mexico. Editor: Priya Yenebere Show Notes: Critical Care Nephrology Critical Care Nephrology: Core Curriculum 2020 by Benjamin R Griffin, Kathleen D Liu, and J Pedro Teixeira. Critical Care Rheumatology Dual-Trained Rheumatologists Take Multidisciplinary Approach to Their Patients Med-Peds to Nephrology Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock by Emanuel Rivers ProMISe: Trial of Early, Goal-Directed Resuscitation for Septic Shock ARISE: Goal-Directed Resuscitation for Patients with Early Septic Shock ProCESS: A Randomized Trial of Protocol-Based Care for Early Septic ShockThe Filtrate: Rinaldo Bellomo and micro circulatory disorders as cause of AKI in sepsis. Septic acute kidney injury: new concepts Comparison of Two Fluid-Management Strategies in Acute Lung Injury (FACTT) The negative trial we accept as a positive trial because of the secondary outcomes. The prime minister of Finland was caught on the dance floor. This is a bad thing? (NY Times) Deferred Consent: A New Approach for Resuscitation Research on Comatose Patients Lactate conversion MediCalc The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Mottling score is a strong predictor of 14-day mortality in septic patients whatever vasopressor doses and other tissue perfusion parameters Critical Care Reviews Podcast: CLASSIC Trial Results Presentation What is the most George Constanza-esque reason you broke up with someone? (reddit) Bonferroni correction The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery in the NEJM. RELIEF, NephJC discussion Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial in JAMA FEAST Trial: Mortality after Fluid Bolus in African Children with Severe InfectionRings of Power on Amazon Prime Why the Hobbit trilogy sucked Industry on HBO Sandman 2022 on Netflix Where did Liverpool FC go wrong with the 2021/2022 Premier League? (Quora) CRRT Academy at University of Alabama with 2020 Robert G. Narins Award Recipient: Ashita Tolwani, MD, MS (YouTube) Life as a Nephrologist podcast on CritCare Nephrology Continuous KRT: A Contemporary Review by J. Pedro Teixeira, Javier A. Neyra and Ashita Tolwani University of New Mexico Nephrology Program. Apply to their fellowship. The Pledge Drive is over, but you can always support NephJC. NephJC is a 501(3)c registered non-profit and all donations are tax deductible in the US.

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Chapter One: Introduction to Renal Function

The Channel Gang discusses the name of their new podcast and then discuss chapter one of The Book.

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FF 76 FINEARTS

The Filtrate Joel Topf Swapnil Hiremath AC Gomez Jordy Cohen Nayan Arora Special Guest Brendon Nuen Editing by Simon Topf and Nayan Arora Show Notes FINEARTS-HF in NEJM FINEARTS Kidney outcomes in JACC FINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes in Nature Medicine discussion in NephJC BARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine) Live Freely Filtered at KidneyWk Swapnil comes out as a SpiroStan post to NephJC TOPCAT TOPCAT primary publication TOPCAT North American results TOPCAT funny business explained AHA/ACC/HFSA Heart Failure Guidelines (PDF) SGLT2i are 2a MRA are a 2b ARBs are a 2b ARNI are a 2b Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone Kansas city cardiomyopathy questionnaire in patients with CKD without a diagnosis of heart failure: https://pubmed.ncbi.nlm.nih.gov/21187260/ GFR slope with steroidal MRAs in HF: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2635 Why Has it Been Challenging to Modify Kidney Disease Progression in Patients With Heart Failure? (JACC) Tubular Secretions Swap: Disclaimer on Apple TV AC: Duo Lingo Plushy (Amazon) Nayan: The Puzzle Box Jordy: Project Hail Mary Brendon has a podcast, The Kidney Compass with Shikha Wadhwani. And he recommends singer-songwriter, Maggie Rogers (YouTube) Joel: The Singularity Is Nearer: When We Merge with AI by Ray Kurzweil Closing music, Tim Yau with The Kidney Connection

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FF 72: Nefecon for IgAN, The NefIgArd part B trial

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

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FF 74: Amino Acids for AKI

The Filtrate: Jennie Lin Joel Topf Josh Waitzman Swapnil Hiremath With Special Guests Pedro Teixeira Jay Koyner Editor Sophia Ambruso Show Notes The article: A Randomized Trial of Intravenous Amino Acids for Kidney Protection NephJC Summary KDIGO Clinical Practice Guideline for Acute Kidney Injury (PDF) Steve Coca study Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials (PubMed) Using Nephrocheck to prevent AKI: Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial (PubMed) Brenner’s Review of protein intake and renal hemodynamics: Dietary Protein Intake and the Progressive Nature of Kidney Disease: — The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Ablation, and Intrinsic Renal Disease (NEJM) Husain-Syed a look at preoperative renal functional reserve and risk of AKI: Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation (PubMed) Dana Fuhrman review of renal functional reserve: The Role of Renal Functional Reserve in Predicting Acute Kidney Injury (PubMed) Use of SGLT2i prevented AKI in the placebo controlled trials. Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 Individuals (PubMed) Assessment of P values for demographic data in randomized controlled trials (PubMed) Tubular Secretions Swapnil The Lord of the Rings: Rings of Power Season 2 on Amazon Prime (Wikipedia) Josh Fortnite (Website) Pedro CRRT Academy at University of Alabama Birmingham (Website) Jay Koyner Slow Horses on AppleTV (Wikipedia) Jennie Linn #KidneyWk Run Club Friday 10/25 at 6:15 am PST Meet in front of Sally’s Fish House ~2 miles. Easy pace (10-12 min/mile) (Strava) Joel Topf Your Honor on Netflix (Wikipedia)

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NephJC’s mission is to increase free open access medical education (FOAMed) pertaining to nephrology, hypertension, and transplantation. NephJC does this primarily by hosting Twitter chats about the latest high impact research in nephrology and related fields. NephJC also participates, sponsors, and supports activities that strengthen the Nephrology social network. One of the primary ways NephJC supports the Nephrology social network is through the Nephrology Social Medial Collective (NSMC). The NSMC internship is training health care professionals to utilize and contribute to the nephrology social network.

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NephJC

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FF 80 KDIGO ADPKD Guideline Draft

Freely Filtered 002

Freely Filtered 065: BEST Fluids

FF 70b Do Over: The PRAECIS trial, predicting severe preeclampsia

Allopurinol Fixes the Numbers and Little Else

Freely Filtered 50: CLASSIC Trial

Chapter One: Introduction to Renal Function

FF 76 FINEARTS

FF 72: Nefecon for IgAN, The NefIgArd part B trial

FF 74: Amino Acids for AKI

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