Thursday, December 18, 2014

Topf gets taken to Dr. Zen's Design Woodshed

I try to design nice posters and one that I was particularly proud of was 2013's Assessment of the Nephrology Blogosphere that I presented at Kidney Week. 

PDF | Powerpoint


A few months ago I submitted it for a design critique at Dr. Zen's Better Posters. Well this tweet surfaced today:


The review isn't pretty:
The colours in the table are not explained anywhere. I am guessing “green”means statistically significant, and “orange” means... a decline in posts over time? Maybe that could be mentioned in the main text at the left. 
The table is big and dense. Again, I wonder if it could be simplified, either graphically (first step: remove the vertical gridline!) or even removed. If I’m reading it right, some of the information in the table is repeated in the graphs to the right of the table. 
The last line of the table - “Totals” - appears to be incorrect. It looks like most of those entries are means, not totals. 
Also, the text mentions 30 blogs, but only 22 are plotted.
I only plotted the 22 with the longest duration of publication. What was the point of graphing KidneyTalk's 6 posts over 2 months? (4 years after the last post, she still owns the URL) 

I also disagree with his critique of the QRcode and bit.ly link. I think QR codes mostly suck and for most people snapping a pic of a URL is quicker and more reliable. I also think every person should have a little home page for their poster where it can be downloaded and supplementary information made available. See the homepage to this year's NephMadness poster.



Overall this was great feedback and I swear my next poster will be better.

Wednesday, December 17, 2014

Over-indexing on medications

I have a patient with CKD stage four, diabetes and hypertension. In fact, I have a hundred patients with CKD stage four, diabetes and hypertension. However, this patient had uncontrolled blood pressures. Here is the nomogram from her home blood pressures:
She was taking once daily furosemide and we changed it to torsemide, for better pharmacokinetics. She returned a month later and her blood pressure was fixed, systolics equally distributed between the 120s and 130s. So a win for Torsemide, or maybe not...

She was excited because she had been reworking her diet and was no longer drinking pop. She was eating more home-cooked meals and really focusing on eating more vegetables and fruits. She was also being more conscious of her sodium intake.

When I walked into the room I was focused on the medication change, because that was my intervention. But the more I spoke with her, the more I began to lean to the lifestyle interventions. She was adopting spontaneous DASH diet:
  • More fruits and vegetables
  • Decreased processed and restaurant food
  • Decreased fructose intake
  • Improved compliance
She denied non-compliance on her previous visit, but her new focus on her health should certainly increase her medication compliance. All of this was in play. 

In the end, medicine is a giant, uncontrolled experiment and correlation does not equal causation. Just because you changed medicine doesn't mean that is was what fixed the blood pressure.

Saturday, December 13, 2014

SIADH and lasix

I remember a time when I thought the treatment of chronic SIADH was going to be revolutionized by the vaptans. These small molecular ADH antagonists would interrupt the disease the precise mechanism of disease. I expected a Banting and Best like revolution. (If you have not seen the story of the discovery of insulin take a moment to watch the movie, Glory Enough for All, especially if you thought the greatest thing to come out of Canada was Tim Horton's)


The initial data was promising with convincing studies on conivaptan and tolvaptan, but something happened on the way to SIADH nirvana.

First the EVEREST trial went sideways. In heart failure:
  • Angiotensin 2 is elevated and blocking it prolongs life
  • The sympathetic nervous system is up-regulated and blocking it prolongs life
  • Aldosterone is elevated and blocking it prolongs life
  • ADH is elevated and blocking it doesn't do a damn thing

With no hope for a heart failure indication the drug was marketed solely as a treatment for hyponatremia where it was shown to be effective. The pitch was that doctors should not discharge people with hyponatremia and tolvaptan was faster and more effective than the previous standard of care. The drug was priced for short-term inpatient use at $300 a pill tolvaptan was a non-starter for chronic outpatient SIADH.
So generous of Otsuka to make the 30 mg dose the same price as the 15 mg

But I held out hope, I felt that as soon as the FDA licensed tolvaptan for ADPKD, the drug would be re-priced for chronic use and the price would come down. In fact during a TEMPO investigator meeting, an Otsuka executive hinted they would lower the price on approval (personal communication). However, despite being the only known treatment that slows the loss of renal function in autosomal dominant polycystic kidney disease, the FDA told Otsuka and the ADPKD community to pound sand.



Somewhere in there, Otsuka changed the labelling and limited tolvaptan to 30 days or less for hyponatremia, so the dream...is officially dead.

But my patients are still alive and they still have sodiums of 125. Demeclocycline, despite being a generic, is very expensive and not a good option. From the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association guidelines on hyponatremia:
The side effects reported for demeclocycline and lithium were such that we recommend not using them for any degree of hyponatraemia.
Fluid restriction, the cornerstone of therapy, is difficult to maintain and in severe cases is insufficient to correct hyponatremia (I'm thinking of patients with negative free water clearance). Urea has a good track record but I have not heard of it being used in the United States. Salt tablets can help, but often are inadequate to correct the hyponatremia.

On the list of possible treatments are loop diuretics. I have tried loops in hyponatremia on a number of occasions and though the math works, in my hands I have not found them to be effective. In the past, I have used loops in hospitalized patients with hyponatremia. The results have been underwhelming. But I know have a loop diuretic success story in a patient with significant but stable outpatient hyponatremia.


I met the patient when he was admitted to the ICU with mental status changes due to a sodium south of 120. This was not his first episode of hyponatremia. We corrected the sodium and restored normal mentation. We did a thorough work-up, looking for the etiology of the SIADH and despite some promising leads that turned into blind alleys, I am quite confident, now, that this is idiopathic SIADH.

During subsequent outpatient follow-up he had persistent hyponatremia with sodiums running in the high 120's. During this time, treatment consisted of salt tablets and fluid restriction. A couple of visits ago I added torsemide, and boom the two sodiums since have been 138 and 134.






Here is the sodium and urine osmolality over time. It plummets after the torsemide is started. This increases the free water clearance.

I also have data on the urine sodium, to get an idea of the electrolyte free water clearance. The change is not nearly as dramatic or convincing.

I have some of the data to calculate electrolyte free water clearance, but I'm missing urine volumes. We can determine the character of the urine from the following formula:

The following percentages represent the fraction of the urine volume which is electrolyte free water. The first three columns are negative, indicating that the urine the patient is producing has less than no free water. Urinating is more like drinking water as urination actually causes the sodium to fall, rather than rise. For a more in-depth explanation of the electrolyte free water calculation, check out this video.

It will be interesting to see if this improvement continues. I now believe that the reason I was underwhelmed when I used loop diuretics in the hospital is that I was working in the compressed time scale of inpatient medicine and only when you stretch the time horizon to months does the drug become effective. I think the reason it takes so long is that loop diuretics need to wash out the concentrated medullary interstitium, thus preventing the ADH from reabsorbing much water. A drug induced partial nephrogenic diabetes insipidus.


Friday, December 12, 2014

Yes, it's a little pocket of insanity but does it have something to teach us?

A few months ago there was a screen shot of a clinic note floating around the internet. It was, in the words of another nephrologist the most passive-aggressive nephrology consult note I have read in a long time:
Patient's sodium dropped further to 120 in the evening. He has had a precipitous drop that I suspect is due to over-diuresis, which does not seem to be a diagnosis within the lexicon of heart failure cardiologists. It is possible that he could have developed SIADH, through a drug side effect. In any case, we have reached the usual place where attempts to fix the heart have blithely interfered with renal physiology, and I am not willing to let his serum sodium decline into the 110s. If we give NS, and he has SIADH, we will worsen his serum sodium. We could use 3% NS, but he is not having mental status changes, yet, and this is bad form for a patient in heart failure. If he is volume depleted, and we use conivaptan, he could develop hypotension which would be difficult to fix. So I seem to have been finagled into ordering tolvaptan, which will hopefully prevent any further decrease tonight. Tolvaptan fixes a number and has not been shown to improve clinical outcomes with chronic use.
Clearly there is a large dose of crazy in the assessment and plan, but it highlights a number of real issues in hyponatremia. Let's dissect the note a bit and tease out the best parts.

The first clam that over-diuresis does not seem to be a diagnosis within the lexicon of heart failure cardiologists seems to be true. A brief survey of google finds a paucity of relevant hits for the phrase and most of those are from nephrologists or family practitioners. Given the frequency that I see patients suffering from this I was a bit shocked at these results.

The next sentence seems a bit preposterous, It is possible that she could have developed SIADH, through a drug side effect. Presuming that a patient with heart failure induced hyponatremia now has a second denovo disease seems a bit of a stretch, but we don't have access to the clinical data and so it is hard to determine if this is true. However the definition of SIADH requires that patients be euvolemic and judging from as much of the story as we know it seems like this patient is clinically hypervolemic. This rules out a clinical diagnosis of ADH, because the release of ADH in heart failure is due to physiological trigger for ADH, a decrease in perfusion. The disease of SIADH is specifically reserved for patients in which there is no physiologic stimuli for ADH release. The presence of heart failure and volume overload, definitionally rule out SIADH.

The next sentence is interesting: In any case, we have reached the usual place where attempts to fix the heart have blithely interfered with renal physiology, and I am not willing to let his serum sodium decline into the 110s. Diuretics increase water and sodium loss, but the cation content of the urine is almost always significantly lower than the plasma cation content, urinary sodium with loop diuretics is typically around 70 mmol/L. So use of loop diuretics cause loss of relatively more water than sodium and result in hypernatremia, except in heart failure. To understand why, one needs to understand electrolyte free water clearance (and an example of using it in the treatment in hypernaatremia is here). The higher the free water clearance, the less prone patients are to hyponatremia. Here are the calculations for electrolyte free water clearance for a patient with hyponatremia due to CHF before and after the addition of loop diuretics:
Before diuretics
In CHF, the patient is actually doing a pretty good job clearing free water. More than half of the urine output is electrolyte free water, the character of the urine is appropriate for correcting the hyponatremia. The problem is not the character of the urine but the amount. The patient just doesn't make enough urine to generate adequate electrolyte free water to account for the water the patient is drinking. Water restriction will be effective for these patients.

So, if the problem is an inadequate amount of urine the logical next step would be to increase the volume of urine with a diuretic:
With diuretics
Unfortunately, though the diuretic increases the volume of urine, it also changes the character of the urine. In this case, it dramatically increases the urine sodium content. This makes the urine almost completely ineffective at removing electrolyte free water and the net result is that the electrolyte free water clearances actually falls with the addition of the diuretic. This is the trap our poor nephrologist is raging against.

The next sentence of the rant: If we give NS, and he has SIADH, we will worsen his serum sodium. We could use 3% NS, but he is not having mental status changes, yet, and this is bad form for a patient in heart failure. I have a problem with this sentence and do not think it is well thought out. The nephrologists clearly believes this patient is over diuresed, we see this situations all the time and they respond briskly to additional fluids. Don't complain that the patient has been overdosed with diuretics and then refuse to provide the antidote for this overdose. I am skeptical of his theory that the patient has SIADH and it is a bit unreasonable to even give a trial of 0.9% saline. In regards to 3% saline, our good doctor might want to take a look at some of the data on the use of 3% saline in heart failure: SMAC-HF (PDF) or Seminars in Nephrology summary. While it is not standard of care the data are certainly intriguing and when the traditional approach is not helping the patient, as apparently is occurring in this patient, it may be worth a look.

The next sentence is regarding conivaptan: If he is volume depleted, and we use conivaptan, he could develop hypotension which would be difficult to fix. Conivaptan is a non-selective vasopressin antagonist, as opposed to tolvaptan which is a selective V2 receptor antagonist. Blocking V1 could cause hypotension as has been reported in multiple case reports. See this open access review.

So I seem to have been finagled into ordering tolvaptan, which will hopefully prevent any further decrease tonight. Tolvaptan fixes a number and has not been shown to improve clinical outcomes with chronic use. This complaint that tolvaptan fixes a number seems a bit obtuse for a nephrologists who was presumably consulted to fix a number. It also implies that tolvaptan is unique in that it has only been shown to fix a number. Well unfortunately, all the therapies of hyponatremia, outside of acute symptomatic hyponatremia have only been shown to fix a number. However given the profound morbidity associated with low sodium, it seems judicious to correct hyponatremia until data proves it is unhelpful. Additionally, to claim in one sentence that you refuse to allow the sodium to fall below 120 and in the next sentence to rail against a therapy that has only has been shown to fix a number seems to belie a profound lack of self awareness.

But keep fighting the good fight against the cardiologists, somebody needs to keep their egos in check. #PracticallySurgeons


Thursday, December 11, 2014

Last chance to vote

The longest tradition in the nephrology blogosphere, the Renal Fellow Network's Nephrology Story of the Year! For five years RFN has been posting the top stories of the year and for the last few years they have been off loading the work to the crowd. So do your duty and vote.

Go vote

Polls close tomorrow. 


And to the losers stuffing the ballot box for "Perivascular Gli1+ progenitors contribute to myofibroblast pool leading to fibrosis in multiple organs including kidney Cell Stem Cell" I will not stand for that!

I'm pulling for Dendritic cell isoketals activate T cells and promote hypertension as covered in NephJC.

Monday, December 8, 2014

The newest nephrology blog: Nephrology Tweetbook

Run by master tweeter Nikhil Shah, Nephrology Fellow at the University of Alberta, Nephrology Tweetbook is primarily a collection of educational tweets with, as far as I can tell, a single long form post on the use of What's App as an educational tool. Very interesting use of the app.

I'm not sure what he is using to post the tweets to blogger, but he would get better, most useful posts if he used the embed code from twitter.

This is what his posts look like:


No active links.

If he were to use the embed tool in twitter it would look like this:







It's a nice addition to the nephrology social media landscape.

Thursday, December 4, 2014

Nephrology is rusting (Updated)

Another year, another horrible match.

Here is the press release: NRMP SMS Nephrology Match for Appointment Year 2015

Some of the highlights:

  • 68 of 134 programs did not fill their positions
  • There were 0.68 applicants for every fellowship position this is down from 1.5 applicants for every position in 2010
Onecurious aspects to the report: the authors wrote:
In AY2015, nearly every nephrology applicant matched, for a 95.2% Match rate.
But take a look at the table:

254 applicants and 254 positions filled, unless an applicant is doing double duty at a couple of programs, it looks like a 100% match rate.

The other fact that I'd like to know more about is there are 141 US medical schools, 6 of those are too new to have any graduates applying to nephrology, that leaves 135 producing 79 applicants. That means at least 56 did not produce a single nephrology applicant. And I bet at least a couple of schools send multiple grads to satisfying careers in nephrology.

What I want is a list of the schools who are failing nephrology and who is teaching nephrology at those locations. Let's put their heads on a stick.


On the other side of that coin is who is teaching at the schools that produce multiple nephrology applicants and what are they doing right. Lets give those teachers a medal.


Can we get the medical school data from NRMP?


Sunday, November 23, 2014

Social media session at ASN Kidney Week

At the 2014 Kidney Week the ASN hosted the first session on social media. The session was moderated by Mathew Sparks and Kenar Jhaveri.

The session had four speakers:

  1. Bryan S. Vartabedian, MD. led off the session with his talk, The Public Physician: The Emerging Role of the Physician in a Connected, Always-On World. 
  2. Margaret S. Chisolm, MD. followed with her talk on Social Media Challenges to Professionalism: Do the Rules Change or Do We Change Social Media?
  3. The next speaker was a rarity at Kidney Week, a patient. Sarah E. Kucharski gave a highly personal story: Patients Turning Likes and Retweets into Healing: Social Media and the Age of the Empowered ePatient.
  4. I anchored the session with a talk titled, Social Media: How to Get Started, which would have more properly titled, Twitter for Nephrons.
A recreation of my talk is below, and you can also download the Keynote slides here.


Dr. Chisolm's persentation is here:


Kidney Talk - Created with Haiku Deck, presentation software that inspires

Matt did a great job of summarizing the Session for AJKDblog.

If you want to see the tweets during the two hour session and the hour afterwards, here is a transcript, (and part 2)with 534 tweets during the session and the one hour after. It is contaminated with other KidneyWk tweets so you have to filter through the list but there are some gems.

Here is a filtered and curated transcript:

Wednesday, November 12, 2014

Play Kidney Week Bingo

Record all of your misadventures at kidney week with Kidney Week Bingo.

Publicize your exploits as you go, by tweeting them with the hashtag #KidneyWkBingo

There will be a prize for the first person to get claim Bingo.

Thursday, November 6, 2014

Kidney Week Approaches


Next week the nephrology world will gather in Philadelphia for the annual ASN Kidney Week. This will be the most social Kidney Week ever. If you are interested in social media and nephrology I'd like to call your attention to a handful of events:


Thursday November 13 ASN Special Session on Social Media. 10:30 in Room 201C. This is the first time social media has been covered a part of the core curriculum at ASN. It should be awesome. ASN has assembled an all-star team to present:
Thursday at 12:45 CJASN and the guys from eJC will be running a session on doing A Better Journal Club. I think I will be speaking for 5 or 10 minutes about my experience with NephJC. Room 104 of the Pennsylvania Convention Center.

Thursday night at 8:30 pm, Blogger Night (after the ASN Presidents Reception). If you like the Neph Social Media Crew from Twitter, Renal Fellow Network, AJKDblog or NephJC, join us for drinks at Field House Philly. It is a sports bar. Look for me in the AJKD hat.

Saturday 10-12 Poster Session. SA-PO661 NephMadness Poster session. Sucks that I'll have to miss late breaking trials, what is usually the best session of the week, but oh well. I'll have to keep up via Twitter.

Saturday 12:30-1:20. NephJC Live. NephJC is doing a live ancillary session. We will take the awesome dynamic of the twice monthly twitter chats and see how well it translates to a live session. We have two young investigators presenting data.

The first is Deirdre Sawinski, MD, Assistant Professor from University of Pennsylvania who is going to speaking on her study of kidney transplants in HIV positive patients.

The second is Francis Wilson, MD who will be presenting data from a recently completed RCT on acute kidney injury. In addition to a platinum pated CV he is an experienced singing waiter so hopefully we will get an ad hoc performance.

NephJC Live will also be awarding the first Nephrology Social Media Awards. We will be giving awards for best tweeter, best new tweeter, best blog post about the conference and best curtain of the conference (best Storify related to ASN Kidney Week) I will have a post on the Social Media Awards later this week-end.

The thing about the NephJC Live is that if you want to come you need to register by Sunday, November 9 so we can buy you lunch. Registration closes on Sunday. Register now.

Thursday, October 9, 2014

Ever heard of Chinese Restaurant Syndrome? Updated

From a letter in the 1968 NEJM:

In a world full of weird coincidences, just days after that tweet, Ira Flatow from Science Friday fame covered Chinese Food Syndrome:


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