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#NephMadness 2024: The Battle For Detox – Antidotes Vs Extracorporeal Therapies – Renal.PlatoHealth.ai

Submit your picks! | NephMadness 2024 | #NephMadness

Anitha Vijayan @VijayanMD

Dr. Anitha Vijayan is the Medical Director for Nephrology at Intermountain Health. Prior to joining Intermountain Health on Oct 1, 2023, she was a Professor of Medicine at Washington University in St. Louis and Medical Director of Acute Dialysis Services at Barnes-Jewish Hospital. Her clinical expertise and research have been primarily dedicated to improving outcomes in patients with acute kidney injury. She was a member of EXTRIP 2019 and is the workgroup chair for ASN AKINOW Recovery work group.

Competitors for the Toxicology Region

Team 1: Supportive Care and Antidotes vs Team 2: Extracorporeal Therapies

<img fetchpriority=”high” decoding=”async” aria-describedby=”caption-attachment-42955″ data-attachment-id=”42955″ data-permalink=”https://ajkdblog.org/2024/03/20/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies/nm24-toxicology-commentary/” data-orig-file=”https://ajkdblog.org/wp-content/uploads/2024/03/NM24-Toxicology-Commentary.jpg” data-orig-size=”844,844″ data-comments-opened=”1″ data-image-meta=”{“aperture”:”0″,”credit”:””,”camera”:””,”caption”:””,”created_timestamp”:”0″,”copyright”:””,”focal_length”:”0″,”iso”:”0″,”shutter_speed”:”0″,”title”:””,”orientation”:”1″}” data-image-title=”NM24 Toxicology Commentary” data-image-description data-image-caption=”

Image generated by Evan Zeitler using Image Creator from Microsoft Designer, accessed via https://www.bing.com/images/create, January, 2024. After using the tool to generate the image, Zeitler and the NephMadness Executive Team reviewed and take full responsibility for the final graphic image.

” data-medium-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-1.jpg” data-large-file=”https://ajkdblog.org/wp-content/uploads/2024/03/NM24-Toxicology-Commentary.jpg” class=”wp-image-42955 ” src=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-1.jpg” alt width=”480″ height=”480″ srcset=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-1.jpg 300w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-6.jpg 150w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-7.jpg 768w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-8.jpg 800w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-9.jpg 600w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-10.jpg 400w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-11.jpg 200w, https://ajkdblog.org/wp-content/uploads/2024/03/NM24-Toxicology-Commentary.jpg 844w” sizes=”(max-width: 480px) 100vw, 480px”>

Image generated by Evan Zeitler using Image Creator from Microsoft Designer, accessed via https://www.bing.com/images/create, January, 2024. After using the tool to generate the image, Zeitler and the NephMadness Executive Team reviewed and take full responsibility for the final graphic image.

Systemic toxicities, especially neurological, are so profound with some overdoses (e.g. baclofen), that some poison control agencies caution against “pulling the plug” until ruling out baclofen toxicity in comatose patients. The overlap of toxicology, pharmacology, and nephrology is a fascinating no-man’s land rarely ventured into by nephrologists.  Many therapeutic agents are cleared or metabolized by the kidneys, making the measurement of kidney function integral to drug development. As a rule, renal elimination significantly contributes to drug clearance when >30% of its active form is excreted in the urine, with exceptions like proximal tubule metabolism (e.g insulin).  I could be a pharmaco-nephrologist at heart – I find the discussion on pharmacodynamics and pharmacokinetics (PK) of an agent in relation to the kidney function so much more fascinating and gratifying than the circular debates on urine Na and osmolality in a patient with hyponatremia. Here’s hoping no one takes away my nephrologist card for that statement! The interplay among toxicology, nephrology, and pharmacology is crucial in implementing timely and appropriate treatments for patients with toxic ingestions.

<img decoding=”async” aria-describedby=”caption-attachment-42957″ data-attachment-id=”42957″ data-permalink=”https://ajkdblog.org/2024/03/20/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies/vijayan-fig-1/” data-orig-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-2.jpg” data-orig-size=”1500,844″ data-comments-opened=”1″ data-image-meta=”{“aperture”:”0″,”credit”:””,”camera”:””,”caption”:””,”created_timestamp”:”0″,”copyright”:””,”focal_length”:”0″,”iso”:”0″,”shutter_speed”:”0″,”title”:””,”orientation”:”0″}” data-image-title=”Vijayan Fig 1″ data-image-description data-image-caption=”

© Vijayan

” data-medium-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-12.jpg” data-large-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-13.jpg” class=”wp-image-42957 size-full” src=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-2.jpg” alt width=”1500″ height=”844″ srcset=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-2.jpg 1500w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-12.jpg 300w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-13.jpg 1024w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-14.jpg 150w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-15.jpg 768w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-16.jpg 1200w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-17.jpg 580w, https://ajkdblog.org/wp-content/uploads/2024/03/Vijayan-Fig-1-174×98.jpg?crop=1 174w” sizes=”(max-width: 1500px) 100vw, 1500px”>

© Vijayan

How do nephrologists get involved in the care of patients with intoxications and determine the need for extra corporeal treatment (ECTR)? In some scenarios (e.g. common drug overdoses like lithium or toxin ingestions such as ethylene glycol), consultations arise for kidney replacement therapy (KRT) at the recommendation of toxicologists, emergency department physicians, or intensivists. Alternatively, nephrologists and/or other specialists recognize systemic toxicity of a drug in the setting of kidney failure (e.g. cefepime or baclofen neurotoxicity in a patient with End Stage Kidney Disease [ESKD]). Collaborating with pharmacists or toxicologists, nephrologists decide the modality and duration of KRT based on the drug’s pharmacokinetics. For example, lithium is a small molecule (7 g/mol) easily cleared by any form of KRT. EXTRIP workgroup recommends HD as the preferred modality of KRT, but I disagree with this recommendation based on our understanding of the pharmacokinetics of Li (Full disclosure – I was a member of the 2019 EXTRIP workgroup). Given its large volume of distribution, a prolonged or continuous KRT will be more effective clearing Li and preventing rebound in serum levels compared to a 3- or 4-hour HD session. EXTRIP recommendations are based on a review of all published literature (even case reports) and not simply pharmacokinetic data. So, if there is limited literature on a topic, the final recommendations may be somewhat restrictive. Hence our understanding of PK of any drug is critical in determining the right modality of ECTR.

For larger proteins (e.g. 1000 – 40,000 daltons), alternative ECTRs like hemofiltration, hemoperfusion, or even plasma exchange might be necessary.  Heavily protein-bound toxins will require hemoperfusion or therapeutic plasma exchange for clearance. In hemoperfusion, the toxin must have low volume of distribution and a binding affinity to the sorbent in the filter, but its use is limited due to technical difficulties and it is not available in most centers. Similarly, molecular adsorbent recirculating system (MARS), approved for liver failure, effectively clears albumin bound toxins (e.g. diltiazem, amlodipine or phenytoin).

ECTR is not easy to perform. Experienced nurses, nephrologists, appropriate equipment, and other resources must be immediately available on site. Also, complications related to access placement, and hemodynamic effects during ECTR must be considered when weighing risks and benefits. Are there other options besides ECTR in drug overdose? Certainly! Antidotes to certain medications emerged over the past 1-2 decades. Examples of an effective antidote are the reversal agents for direct oral anti-coagulants (DOACs).  Initially, about a decade ago, treatment of dabigatran overdose involved supportive care and hemodialysis. Now idarucizumab (a monoclonal antibody to dabigatran) is the mainstay of treatment! Glucarpidase is FDA approved  for methotrexate toxicity in patients with lymphoma and leukemia receiving high dose methotrexate (HDMTX). A recent abstract, published at the American Society of Hematology demonstrated that glucarpidase was associated with almost 2.5 fold higher odds of renal recovery (95%CI, 1.38-4.27). This antidote is not cheap by any means – approximately $41,000 per vial at one source – and is not stocked at all hospitals.

So, is there only one way to skin a cat?  The answer is no. Ultimately, the choice of treatment for toxic ingestion involves teamwork and the consideration of patient needs, institutional resources, and the availability of ECTR and/or antidotes. As much as I enjoy discussing CKRT and prolonged intermittent kidney replacement therapy (PIKRT), this may not be the right treatment for patients if an antidote is readily available or if toxic effects are not severe and life threatening.  Similarly, for a patient with methotrexate toxicity with AKI, if glucarpidase is not available at your institution, then KRT should be started immediately. Understanding the drug’s pharmacokinetics is essential in implementing the best ECTR modality . And always remember that as nephrologists, we do have an integral role in the management of patients with toxic ingestions at our institutions.

<img loading=”lazy” decoding=”async” aria-describedby=”caption-attachment-41566″ data-attachment-id=”41566″ data-permalink=”https://ajkdblog.org/2024/03/01/nephmadness-2024-toxicology-region/watersplashofthewashingmachinedrum/” data-orig-file=”https://ajkdblog.org/wp-content/uploads/2024/01/NM24-Toxicology-Extracorporeal-therapies.jpg” data-orig-size=”5184,3456″ data-comments-opened=”1″ data-image-meta=”{“aperture”:”0″,”credit”:”Shutterstock”,”camera”:””,”caption”:””,”created_timestamp”:”0″,”copyright”:”Copyright (c) 2017 NoonBuSin/Shutterstock. No use without permission.”,”focal_length”:”0″,”iso”:”0″,”shutter_speed”:”0″,”title”:”Water,Splash,Of,The,Washing,Machine,Drum”,”orientation”:”0″}” data-image-title=”NM24 Toxicology Extracorporeal therapies” data-image-description data-image-caption=”

Copyright: NoonBuSin/Shutterstock

” data-medium-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-3.jpg” data-large-file=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-18.jpg” class=”wp-image-41566 ” src=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-3.jpg” alt width=”380″ height=”253″ srcset=”https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-3.jpg 300w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-18.jpg 1024w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-19.jpg 150w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-20.jpg 768w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-21.jpg 1536w, https://renal.platohealth.ai/wp-content/uploads/2024/03/nephmadness-2024-the-battle-for-detox-antidotes-vs-extracorporeal-therapies-22.jpg 2048w, https://ajkdblog.org/wp-content/uploads/2024/01/NM24-Toxicology-Extracorporeal-therapies-1200×800.jpg 1200w” sizes=”(max-width: 380px) 100vw, 380px”>

Copyright: NoonBuSin/Shutterstock

– Guest Post written by Anitha Vijayan @VijayanMD

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

Click to read the Toxicology Region

Submit your picks! | #NephMadness | @NephMadness