Super fun discussion on Twitter that has spilled out over the last few days. It began with this tweet about Nayan’s take on the latest MRI imaging during dialysis.
The original article is here and I’m a bit embarrassed about my sensationalization being a bit overwrought.
Forunaltely, it did trigger a great rolling conversation about the future of dialysis and by extension, nephrology. It may be difficult to recreate the discussion from that original tweet, so here are some key tweets:
I remain hopeful for the day when most of the job for ESKD is managing implantable artificial kidneys or xenotransplants / kidney on a scaffold grown in vats. We need to get to the point where most dialysis is relegated to the hospital.
I will make a bolder prediction : the HD business landscape will be dramatically different in the next 5 years: low margins, "harvesting" of the "pipeline" and patients by COVID and PASC, hopefully deployment of SGLT2i/MRAs/GLP1 at scale & a couple of fiscal crises lie ahead.
— ChristosArgyropoulos MD, PhD FlozinatorInChief (@ChristosArgyrop) March 13, 2023
This whole thread is like just about every dinner meeting lately. It starts with a cool study about the effects of the dialysis on the brain and ends with all our personal forecasts about CKD business.
This is another downstream "effect" of VBC. I am getting bored!!
But this prognostication is focused on emerging transplant technologies and fails to capture the full breadth of nephrology transformation that we are seeing. With the emergence of Flozins, GLP1 agonists, MRAs (both steroidal and non-steroidal) as well as the increased interest and development of novel treatment targets, it is not a leap to say that nephrology in 10 years will look very different than it is today.
How will we mark that development? My poll of when will more than half of transplants come from non-human sources is a specific and quantifiable time that will represent a sea change in transplant. A marker that represents a change not in potential but in delivery. So how will we mark that moment in nephrology at large? I would argue that it happens when we see consistent year over year fall in the number of prevalent dialysis patients (in-center and home) for four consecutive years.
So how long until the combination of slower CKD progression, increased transplantation, and, unfortunately part of the equation, continued stagnation in dialysis longevity, result in consistently falling dialysis prevalence?
A ten percent reduction in sodium drops it from stone cold normal to rather significant hyponatremia. This is a great example of how precisely sodium is regulated. Sodium regulation is tighter than all other ions. Look at a CMP with calcium, phosphorus, and magnesium added in. (Data is from UCSF).
BUN (233%) and creatinine (117%) are not regulated anywhere close to how electrolytes are regulated. Get those guys out of here.
And, the sodium (7%) and chloride (10%) range are nearly identical. Outside of the anion gap, I almost always ignore chloride.
So let’s simplify this and remove the outliers and shadow.
Look at how tightly sodium is regulated. Regulation of second place, calcium, is THREE times as relaxed.
Every electrolyte is important, but regulating sodium regulates the tonicity in all 42 liters of the internal ocean. Apparently, this is important and sodium is allowed to wander only slightly.
The destruction of Twitter seems to continue. Tweet threads like this do not make me optimistic about the future, so download your Twitter experience before Twitter.com is nothing more than a empty website.
[1/4] One of the fascinating things is watching Twitterβs behavior change, hour after hour, as various microservices go offline. Itβs a real testament to that approach that things mostly work as various features wink out of existence.
After requesting your archive you need to wait for twitter to package up your experience. When they do you will see this on your time line
And this in your email
After I requested my Twitter Archive, it took two days for mine to be available. This is longer than I have seen in the past, makes me think there is a mad rush for the door and a lot of people are doing this.
When you click on the tweet it asks you for your password and then lets you download your Twitter Archive.
It can be a big file. Mine is 5.1 gigs. The archive it is a folder containing two other folders and a text file called Your Archive.html. Launch that and you will be greeted with this.
Clicking on “Tweets” allows you to see your entire history with a nice search function on the right.
I don’t know where Twitter is headed but it doesn’t seem good and I think in the next month or two (weeks?) there is a real possibility of going to twitter.com and seeing a blank page.
#NephTwitter has developed into a wonderful community and if Twitter disappears the community will be forced into a diaspora. NephJC has the podcasts, the newsletter, and the website to communicate our next moves. If you do not subscribe to the newsletter, now would be a good time to do so.
This coming Tuesday, November 15th, NephJC will be discussing EMPA-Kidney and after that discussion ends at 10pm we will be hosting a Twitter Spaces audio chat to discuss about what to do “After Twitter.”
In the mean time, if you have been investing in Twitter for a year, five years, ten years, fourteen years, then you should download your Twitter archive.
To do this go to your profile page and press “More” It will look like this. Then click on “Settings and Support”
From “Settings and Support” Click on Your Account and then Download an archive of your posts.
Twitter will ask you for your password and then it will e-mail you a note when the archive ready to download.
A number of years ago, I was invited to write a chapter introducing sodium and water for a new medical text book under the Scientific American brand. I remember being disappointed that I didn’t get hypo- or hypernatremia and being stymied for awhile before I figured out how I wanted to the topic. Ultimately, I had a great time writing the chapter and, at least at the time. I was quite proud of the work. The textbook was somehow abandoned somewhere between inviting the chapter authors and publication. The publisher pivoted to some online component that was supposed to rise out of the ashes of the text book and they asked me to do additional work. I never did that work and they never asked a second time, so I don’t know if that ever came to fruition.
Anyways, this chapter has been sitting in the bowels of my Google Drive for years.
I hadn’t thought about this until recording chapter seven of Channel Your Enthusiasm podcast where we are reading through Burton Rose’s classic Clinical Physiology of Acid Base and Electrolyte Disorders. In Chapter 7, Rose discussed using simple math to predict the changes in intracellular and extracellular fluid volume following various fluid and solute challenges. This is exactly what I did in my Scientific American chapter. I found the exercise to be a profound moment of understanding.
USRDS tracks the eGFR of patients starting dialysis, and from the mid 90s through the first decade of the 21st century there was a steady increase in the average GFR at the initiation of dialysis.
While the trend began before 1999, I suspect that the introduction and widespread adoption of the MDRD formula, which revealed that older people with relatively modest increases in creatinine had profoundly low GFRs, had a role in this. This recognition was further reinforced when KDOQI introduced the CKD stages in 2001 that called CKD Stage 5, “Kidney Failure” and implied that CKD stage 5 was a synonym for dialysis.
The trend of starting dialysis at earlier and earlier GFRs reversed following the publication of the IDEAL Trial in 2010. IDEAL showed no survival advantage for starting dialysis at a specific GFR compared to waiting for uremic symptoms that forced the patients to start dialysis. Dialysis is not a cosmetic procedure, we only do it when it is essential.
But deciding when to initiate dialysis is not as easy as waiting for a patient to become uremic, because guidelines, based on retrospective data, tell us to avoid central venous catheters and place arteriovenous access for hemodialysis. Grafts are pretty easy because they usually mature and are ready to use in less than a month. Fistulas, on the other hand, take time to mature and often fail to mature at all.
In this RCT of clopidogrel to assist in access maturation, two thirds of all fistulas were deemed inadequate five months after placement. A few more may have matured after that, but I don’t think it is likely and with a patient nearing dialysis, I suspect new plans for an alternative access will be sought out by that time.
So planning for hemodialysis, with a fistula really means trying to predict where a patient will be six in the future. Learning to do this is the art of taking care of patients with advanced CKD. During my career I have repeatedly been surprised by how long patients with advanced CKD can hold off and delay dialysis. Every time these patients come in I would bring up a list of their old GFRs and marvel how long they had been going with a sub-20 ml/min GFR. Often this would stretch for close to a decade. So when Navdeep Tangripublished his Kidney Failure Risk Equation (KFRE) I felt validated as it showed that patients with low GFRs avoided dialysis longer than doctors (and patients) expected.
How the Kidney Failure Risk Equation (KFRE), physicians, and patients did at predicting the initiation of dialysis. Below the line of identity means over predicting dialysis, over the line of identity is under predicting.
On Wednesday I posted a typical case to twitter and asked people to decide between sending the patient for fistula creation now or to wait. It is the same patient in both polls, but in the first I provided the eGFR, while in the second I provided the KFRE result.
Same patient; wildly different results. I think it does a nice job of showing that people underestimate patients’ prognosis when they look at eGFR. I find I use the KFRE when talking with patients all the time. It helps reassure people with good kidney function when they are first diagnosed with kidney disease and it helps me when they have advanced CKD when trying to figure out the timing of access procedures and more detailed discussions of end-stage kidney disease.
This web app by Amarnath Marthi allows you to play with the variables in nearly real time to get an idea of how the equation works (though I wished it would let me use mg albumin / g creatinine). Note that the risk of ESRD goes down as the patient’s age goes up. This is due to the competing risk of death becoming larger with advancing age.
Below are links to some of the great tweets that emerged from these posts. It always amazes me the breadth and depth of knowledge I find in my Twitter feed.
If a "good" 80 would send for AVF now, if fair to frail would start HD trial with CVC when the time hits
There is missing information – what was his rate of progression to date? , does he have comorbidities? A scoring system makes a mockery of the clinicians ability to individualize care for the person in front of him. Do betterβ¦
When death & dialysis are competing risk factors, the rate of GFR decline is so critical in making AV access decisions. This patientβs GFR loss is 1-3 ml/min/year so will hold off on AVF placement. If he reaches ESKD in 4-5 years (at age 85) proceed with AVG
Fistula candidate means just that. Many other variables need to be accounted for to get a functioning fistula.
How about taking into account the data that creating an avf can slow down renal fx decline. Articles by Tom Golper from Vanderbilt and some others. Would that change the plan https://t.co/MKIHtno07i
Was not aware of this data, though it seems a bit soft. But if it pans out, it would be practice changing, at least for me.
So this 80 yr old patient with gfr of 14 has only 31% probability of needing dialysis at 5 yrs?? That seems pretty low. Not sure the equation remains validated well at this age group.
This last tweet is here because in my reply I post a reference that shows that the KFRE actually cover estimates need for dialysis in the elderly not underestimates.
The kidneys design is a cool solution to the problem, how do you make a filter that removes poisons you may have never seen before? Make it throw out everything and then keep the things you need.
— NeuroBill – @neurobill@mastodon.cloud (@NeuroBill) November 10, 2021
Correcting sodium is generally not the hard part.
Correcting it at an appropriate rate is how a nephrologist earns his keep and/or loses sleep.
I made the video with Keynote, it is a single slide with a lot of animation. Here is the slide (all 750 kilobytes):
Creating the animation just takes patience. This slide has 44 steps to the animation. It is a mixture of build ins, actions, and build outs.
Once I had the animation perfect I used “Record Slideshow…” to record the animations and my narration, then exported the movie using “Export To Movie…”
When it became apparent that COVID-19 would not just be a medical event that happened over there but was going to affect everything I started jotting some notes. They have remained in Drafts for over a month, but now I am going to start publishing these diary entries mostly just to document the strangest, most unexpected experience of my medical career.
After the second week of peak COVID; a week where I had my own COVID scare, worked har, lost patients, and had a Quarantine Zoom Seder; I was relaxing on twitter, feeling pretty good when the NEJM dropped the first data on Remdesivir. It was a report on the compassionate use program. One of our patients at St Johns had been part of the program. The data looked promising and it was being published in the highest journal of the land. I had seen the article after reading about it from one of the top doctors on Twitter, Eric Topol.
Big for #COVID19 therapy: the compassionate use results for remdesivir in 53 patients looks very encouraging, especially in very sick patients on mechanical ventilation with 18% fatality (only, expect > 50%) and overall 68% improvement https://t.co/oP8eDK6jYL@NEJMpic.twitter.com/9kisPxy1un
It may not be my most populat tweet but it is certainly in the top 10.
It may have been popular but mostly at my expense. I was not ratioed, but it sure felt like it. Comments were about 10:1 opposed to my enthusiasm. Here are a few of the best:
Thatβs not a good tweet Joel
— Swapnil Hiremath @hswapnil@bsky.social (@hswapnil) April 11, 2020
You thinking about running for president @kidney_boy??? Itβs a cohort study with no control group and 13% loss to follow up of 61 patients. Not even a historical control??? How did it get into the @NEJM???
— Buck Dancer, MD π«π« (@BuckDancerMD) April 11, 2020
My Tweet was the lead in coverage over the reaction to the study by WebMD. No, they didn’t reach out to me for comment.
So now it seems like I own remdesivir. See Waitzman’s comment when the Executive Deputy Editor of NEJM presented Grand Rounds at Beth Israel.
Dr. Hamel, when asked about @kidney_boy's favorite remdesivir trial: -We are publishing more case series and case reports than we used to. -But publishing "good enough" research faster may be more useful and save more lives than "perfect" work.https://t.co/jpQyrUqbtm
And this week, the study, and my tweet were part of The Curbsiders
And I was Exhibit A in the ID Journal Club Chat (#IDClub)
Previously, there had only been a case series of 53 patients treated with RDV under compassionate access. 2/3 pts had some clinical improvement but pt selection was unclear & there was no comparator. The response on #MedTwitter was divided. Was the criticism warranted? #IDJClubpic.twitter.com/JquctIEORC
I think it was an unfortunate tweet made too quickly in the evening. I was hoodwinked by the authority of the NEJM and Topol. It probably dropped my credibly as a science communicator. But the importance of this moment is quickly approaching zero as placebo controlled remdesivir data (both positive and negative) begins to emerge. Live and learn. Tweet and move on.
We tweet and think the tweet evaporates after a day or two (actually, that’s particularly optimistic, most disappear after an hour or two) but occasionally a reply can come from the distant past like a message from a deep space probe.
Today, someone replied to a tweet I wrote in May of 2019.
Hi Joel. Is there any way I can access a recorded link to your presentation?
I’m not sure if The Drug Policy Organization ever posted the webinar, but I now realize that I never posted the slides to my website. So here they are:
