Kidney Week is approaching. After a two year hiatus we are going to meet in person again in less than a month. I am very excited. NephJC and the NSMC will have a great presence and it should be fun.
Sunday is the least attended day of the conference. It is a half day and most people leave that morning and miss the whole day.
Sunday’s Plenary session should begin at 9 not 8 to encourage people to go out and socialize Saturday night and to make room for…
7:30 AM Sunday have 5k run/walk. Do a different kind of social event. Raise money for a local charity. Let nephrologists form teams. @VUMCKidney team. @arkanalabs@goKDIGO all could have shirts and shared a moment.
These national meetings need to move past charging hundreds of dollars for slideshows and be more about being with your people.
I spoke before thinking. I spoke loudly. I spoke and I hurt people. People who mean a lot to me. I hurt a mission that means everything to me.
I tweeted in anger and I said things to an imaginary place inside my phone that I would never say in person.
I spoke without grace. I spoke with a foul mouth.
We say it all the time, “Don’t Tweet Angry,” and it’s because we know the internet has a way of making us forget there are humans on the other end of the tube. In this case, the humans were people I know. People who are passionate, conscientious, dedicated, and good.
This is bad. This is not who I aspire to be. I am sorry.
I hurt people that are contributing to this great collective, this great educational mission. #NephTwitter is the greatest FOAMed effort in Medicine. #NephTwitter is what every specialty in medicine should aspire to. And the Nephrologists running The GlomCon Fellowship are doing a great job building #NephTwitter. I should never do anything to tear this down. I am profoundly sorry.
Let’s keep AngryTwitter as far from #NephTwitter as possible.
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.
As I was spelunking in the depths of my hard drive I came across this document from the end of 2013. We had completed the inaugural year of NephMadness and after returning home from Kidney Week, Matt, Edgar, Kenar and myself put together a proposal to make NephMadness a recurring event.
It is remarkable that we were putting the pitch together in November and December when the contest would launch in March. Now NephMadness is a 9 month month process with planning usually beginning in June.
Some notes from the document. In 2014, we were still trying to figure out how to determine the winners. I love this paragraph, especially, “One down side of this is that it will make the contest appear rigged, which it actually is.”
I also like this part which gives you an idea of how small not only NephMadness was in 2013, but how small the footprint for online nephrology education was:
1. We were highlighted at the AJKD editorial board meeting to a geographically diverse, packed room. Dr. Levey asked how many people participated in the first NephMadness and almost no one raised their hand.
2. A day later we demonstrated NephMadness to a room of cutting-edge educators. I got the feeling, besides the usual suspects (Edgar Lerma, Pascale Lane, Tejas Desai, etc.) no one in the room had heard of the campaign. The crazy bit was, I don’t think many had heard of PBFluids.com or NephronPower.com. This really reinforced to me how limited our exposure was. We had reached out to a lot of people and had dramatically boosted the traffic to the blog but to a large extent we were preaching to the choir.
And lastly, in the publicity section we were excited about getting featured on Dr. Mike SevillasPodcast, which has since gone defunct after 372 episodes!
So here it is for all your NephMadness nostalgia needs…
I’m in the taxi leaving #NKFClinical (or at least I was when I started writing this) and if it wasn’t the first in-person meeting that most of us have been to since the onset of the pandemic, it would be remembered as “the one where Korsuva was launched.”
Room key and business cards from the Vifor Army at the meeting
During the meeting there was a buzz about this drug. And the buzz was around the two phase-3 trials, KALM-1 and KALM-2. The buzz is around the decreased effect size from KALM-1 to KALM-2. Difelikefalin met it’s primary endpoint to reduced severe itching in KALM-2, but the effect size is notably smaller than in KALM-1.
The results from KALM-1The results from KALM-2
The effect size could have been larger, the same, or smaller than KALM-1. I’m not sure how much shade should be cast that it turned out to be smaller, especially as it remains better than placebo.
But my primary concern is that focusing on effect size misses the point.
We are used to prescribing invisible drugs; drugs that move a magical end point like cholesterol or blood pressure. Lowering cholesterol does not make patients feel better it just loads the dice so that when fate rolls them every year your patient is less likely to have an acute MI. Same with antihypertensives, SGLT2 inhibitors and almost everything we use except for pain killers. If the patient asks the doctor if the drug is working it is an invisible drug. If the doctor asks the patient if the drug is working it is a visible drug.
I was a sight PI on KALM-1, which means I am one of the few nephrologists who has real world experience with the drug. During KALM-1 I saw people have remarkable response to study drug and I saw people people have no response to study drug. Since I was blinded, I assumed that everyone having a good outcome was on drug and everyone without a response was on placebo. That is always a fairy tale and I now know that wasn’t true. Both KALM trials showed a big placebo effect (not as big as difelikefalen, but big). The placebo effect was large enough to convince me that all the success I have seen with diphenhydramine, gabapentin, steroid creams (none of which have robust supportive data), was likely just placebo effect. And now we are about to get the opportunity to switch everyone who has failed placebo to start an effective drug. But the wonderful thing is we do not have to just hope the drug is working, we can just ask our patients. Use it for a few months and ask people if they are better. No need to worry about the statistical effect size, all we need to do is assess the effect size in the patient in front of us. If the drug is not working stop the drug. However, be aware, a few weeks later the patient may tell you how much they liked it and that it was helping more than they recognized. My study patients were most vocal after the study concluded and everyone stopped study drug and went back to usual care. Multiple patients begged to enroll in extension studies, different investigations, anything to get access to difelikefalin…because uremic pruritus is miserable.
Difelikefalin is the first drug we have in nephrology whose specific purpose is to alleviate symptoms. This is a different type of drug and we need to retrain ourselves to shift our view on effect side.
After I wrote this, I was made aware of two other anti-itching drugs that I was not aware of. I have no experience with them, but I thought I would list them here:
Nalfurafine a K-opioid-receptor agonist which is approved in Japan (2009) and South Korea (2013).
Nalbuphine, a mixed k-opioid-receptor agonist and partial-opioid antagonist. It has central nervous system effects and may cause dysphoria. It has abuse potential, though it was initially a schedule II drug, it no longer is.
COI: I was a site PI for KALM-1. I recorded a video testimonial for difelikefalin a few years ago. I have attended an advisory board with Cara, the company who developed the drug. I have participated in these because I have seen the product relieve suffering. I would not support a product I did not believe in.
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 better…
When death & dialysis are competing risk factors, the rate of GFR decline is so critical in making AV access decisions. This patient’s 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.
I had the opportunity to give grand rounds at Ascension St John hospital, my home institution, last week on the new CKD-EPI equation that calculates eGFR without a race modifier.
PowerPoint:New eGFRequations! Now with less racism (69 MB) Note: I create, rehearse and deliver the presentation in Keynote. The PowerPoint version is a simple export of the Keynote presentation and often looks like garbage. If you want to see the presentation as it was meant to be, use Keynote.
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.
Recently, when talking about social media and medical education I have been comparing it to traditional medial education. Some media is locked into one camp or the other. Textbooks are a bastion of traditional medical education. The complexity of writing and publishing a physical book results in a cost structure so high that it can’t given away. Textbook costs for some corners of medicine have risen to absurd prices.
I had no idea pediatric nephrology text book prices were from another planet. pic.twitter.com/VbUE44VnK8
But I have a text book that has crossed over from traditional medical education to FOAMed. By making the Fluid, Electrolyte, and Acid-Base Companion a free download from this site I can get an idea of how much the price of a textbook is a barrier to wide adoption. The Companion went through one print run of 1200 books. We never did a second printing. All of them were sold. Any copies now available on Amazon are only available because of a robust secondhand textbook market. But since September of 2017, I have made the “Whole Enchilada” available for free on this site. The Companion is available as a simple PDF for anyone to download, redistribute, mark-up, and copy.
We sold 1200 printed copies. So how do we do with downloads? We get about half that number every month and have been averaging that for the last 5 years.
Download numbers from WordPress. I have been on WordPress for 46.5 months.
The Free in FOAMed is important. But I also think providing the document in a flexible, universal format like PDF that doesn’t require a specific reader app is also important. Remove as many barriers for the user as possible.
Why this post? Because I need a reference for a chapter I’m writing. I know it sounds circular, but a reference to a blog post seems better than “personal communication.” Look for this chapter on nephrology and social media to be published in a textbook in the next year or two.
