Monday, December 28, 2015

Teaching Awards

I know this is vain, even for a personal blog, but I need a place to keep track of these.

Original (PDF)

Sunday, December 20, 2015

Misplaced concreteness

Nephrology, more than other specialties is plagued by misplaced concreteness. We get false senses of precision because of the myriad of equations that spit out results to the milliliter. All of those equations from Kt/V, to water deficits, to IVF brain teasers depend on an estimate of total body water.

Everyone knows the rule of thumb that young males are 60% water, young females are 50% water and the percent body water falls as people age or get fatter.

Going beyond these rules of thumb, how is total body water measured empirically? The gold standard is heavy water dilution.

This works by giving a sample of heavy water and then waiting for it to equilibrate. Then the investigators measure the heavy water content of exhaled water vapor or a blood sample, the fraction of the water that is heavy water will be equivalent to the fraction of total water which is heavy water. Then since one knows the amount of heavy water given to the patient, one can calculate total body water.

When this is done, or when one reviews the primary literature, as was done in this study the numbers are a little different.

The drop in total body water (in red) in men never gets down to 50% as predicted for the elderly, and in women almost all of the numbers are below 50% and the trend to lower percentages through aging holds if you ignore the 9 women over the age of 70. Of note, these patients are not that obese, see BMIs in blue.

The above study lead to the development of the Watson equation to determine total body water. The Watson equation uses age, weight and height for men and height and weight for women:

  • Males: TBW (in liters) = 2.447 + (0.09156 × age) + (0.1074 × height) + (0.3362 × weight)
  • Females: TBW (in liters) = –2.097 + (0.1069 × height) + (0.3362 × weight)

This study in peritoneal dialysis patients (peritoneum empty) showed surprisingly close relationship (R=0.92) between deuterium dilution and the Watson equation:

Another study of PD patients demonstrated one of my pet peeves, the major effect of obesity has on total body water.

The chart is a bit difficult to understand. The Y axis shows the Watson calculation of total body water minus heavy water dilution. So negative numbers indicates cases where the Watson method underestimates TBW. When the Y-axis is positive the Watson calculation overestimates TBW. The X-axis expresses obesity as body fat over body water. Really? fat over water. You couldn't just graph this versus BMI?

Wednesday, December 9, 2015

IV Fluid Brain Teaser: Salt versus Saline

Everyone knows that if you give a liter of saline, all of it remains in the extracellular compartment.

But what if you give a patient just the salt from the saline and none of the water? How much does the solute contribute to the increase in the extracellular volume? How does 154 mmols of NaCl affect the size of the extracellular and intracellular compartments?

Assume the patient is a 70 kg lean young male with a serum osmolality of 280 mOsm/kgH2O. Ignore any renal losses during the process.

For full credit fill out the following:

Total body water:
Size of the extracellular compartment:
Size of the intracellular compartment:

Tuesday, October 13, 2015

Please fund my #DreamRCT, it is just embarrassing how little evidence is found in hyponatremia

So I checked in at DreamRCT and noticed that my DreamRCT is no longer in the top five.

I'm a big boy and can take this (very minor) form of rejection but I do want to plead my case for a moment. You can read the entire description of my DreamRCT here. One of the dirty little secrets of nephrology is the almost total lack of prospective data on hyponatremia. There are a number of RCTs with regards to tolvaptan, conivaptan and other approved, and soon to be approved, vaptans. But after those there is an evidence desert populated by only a few mirages made up of case reports and retrospective analysis. From this scant data we have built a comprehensive and detailed model of how sodium acts in the body and the importance of osmoregulation. But thats like theoretical physics without a supercollider. We need to test the model with real data.

Think about the fact that hyponatremia is the most common electrolyte disorder. We order metabolic profiles on every patient, every day, but when it comes to interpreting those results we might as well be reading hieroglyphics.

RCTs are difficult and expensive but there are particular areas where we should require them prior to treatment. One of these corners is when we treat people with no symptoms and we are effectively treating a number. High cholesterol, high blood pressure, and low sodiums are three such areas, however hypertension and hypercholesterolemia have both gone through the right of passage called a randomized controlled trial. I am confident that my patients with asymptomatic hypertension benefit from treatment. My patients with coronary disease and hypercholesterolemia will live longer and better with treatment with a high potency statin. On the other hand, patients with sodiums of 129 and no apparent symptoms are supposed to be at higher risk of falls, have a higher mortality from heart and liver failure. Does treating them reduce these risks?


We can do better. Hyponatremia is the most common electrolyte disorder found in patients, we owe it to them to have real, prospective, data to answer these questions.

Go to UKidney to vote for my trial: No hyponatremia modification in asymptomatic hyponatremia. Thanks.

Friday, October 2, 2015

DreamRCT begins

DreamRCT is a creative writing project for nephrologists. The assignment is to scour the landscape of nephrology knowledge for a corner that is dominated by dogma and retrospective evidence. Once the target is identified, the writer needs to summarize the gaps, and think up a creative way to shine science's greatest flashlight on the subject, a randomized controlled trial.

We have recruited 16 people to submit DreamRCTs which were published today on MedPage Today. Thanks Ivan, Kristina and Elbert. It is a amazing collection of creativity; there are trials on kidney stones, electrolytes, dialysis, proteinuria and lupus. Please go check them out; read them and see which are great and which should be relegated to The Journal of Craptology.

After reading the DreamRCTs move on over to Jordan Weinstein's excellent UKidney where it is time to channel your inner Mark Cuban and play Shark Tank with the DreamRCTs.

Which trial should be funded which shouldn't. How much should each trial be awarded. You will get $100,000 to distribute among the trials. Think KickStarter meets NIH. You will not be alone in this endeavor. We have recruited an expert panel of clinical researchers to score the trials. At the conclusion of the contest we will look at how the experts spent their cash and how the crowd did. We will also award a small prize to the funder whose distribution best matches the expert panel.

DreamRCT only works if we get a critical mass of people to participate. Please check out the trials at MedPage Today and then go to UKidney to vote with your (completely virtual, don't ask me for a refund) dollars. Announce the project at morning report, assign your fellows to vote and then submit discuss and submit your own DreamRCT, because in the end DreamRCT is not just a game but a shorthand expression for what we need to do to fix nephrology and heal our patients.

Tuesday, September 1, 2015

Please go and comment on this month's CJASNeJC

eJC, you know the other online nephrology journal club, invites people to write introduction to their monthly journal club.

Last August I worked with Bilal Saleem to review and summarize a neat study on anti-PLA2R in membranous.

This year I worked with Saiyed Muddasser on an article looking at cold dialysate for cardio protection. Take a look at the summary and then go to the eJC site and make a comment.

Tuesday, August 25, 2015

#OUWB Renal question: The bad quiz question

Apparently there was a weekly quiz and one of the questions was as follows:

And I received an e-mail asking e to answer this question. Lets go through it item by item. The stem sets up a patient with diarrhea induced metabolic acidosis. This is a cause of non-anion gap metabolic acidosis due to GI loss of bicarbonate.

Choice A. This is wrong. The filtered load of bicarbonate is dependent solely on the plasma bicarbonate concentration. The lower bicarbonate concentration seen in all metabolic acidosis would cause decreased not increased filtered load.

Choice B. This is right. Ammonia is produced in the proximal tubule in response to metabolic acidosis and hypokalemia. This is why ammonium excretion is able to be up-regulated due to an acid load. Titratable acid is fixed and can't accommodate an increased acid load. The ammonia production varies depending on metabolic need and chronic diarrhea would up-regualte ammonia production so it could be converted to ammonium in the medullary collecting duct to help clear the excess acid load.

Choice C. This is right. Hydrogen secretion is increased in the distal nephron in response to the metabolic acidosis. This is needed to replace the bicarbonate lost in the stool. Every hydrogen in secreted int eh distal nephron synthesizes a new bicarbonate molecule for the body.

Choice D. This is wrong. Diarrhea causes a non-anion gap or normal anion gap metabolic acidosis.

Choice E. This is right. Hydrogen secretion in the distal nephron is stoichiometrically equivalent to producing new bicarbonate, one cannot happen without the other.

Some of the social media action around this question:

Monday, August 17, 2015

Big anion gap or biggest anion gap?

One night that I was on call, I received an interesting patient from the ED.

The patient was confused but walked into the ER and was able to give at least a partial history. They did some initial chemistries and called me with the following results:
This is the kind of lab that grabs your attention.

With that glucose the first thought should be, "Is this DKA?"


Beta-hydroxybutyrate: 6 mmol/L

I try to account for the anion gap. So I look at all the anions I measure and see how well they explain the gap. And if I can't account for the majority of the gap I have difficulty sleeping. This patient's gap was 51, 12 is normal which leaves 39 to account for. Only 6 can be accounted for with beta-hydroxybutyrate.

"Is there a lactic acidosis?"



That still leaves 17 mmol/L of unexplained anions.

Next step, look for an osmolar gap.

Measured osmolality 348
Ethanol level 0



An osmolar gap of 32 is a profound osmolar gap. We ordered fomepizole and started hemodialysis for presumed toxic alcohol poisoning. 

The alcohol screen came back the next day:

ETHYLENE GLYCOL, SERUM = 0 mg/dL (Reference Range: 0.0-5.0 mg/dL)

PROPYLENE GLYCOL, SERUM = 8.1 mg/dL (Reference Range: 0.0-5.0 mg/dL)

Propylene glycol is normally due to the solvents used to dissolve IV drips. So usually we see problems in patients who have been in the ICU for awhile.
Arroliga AC

Propylene glycol is also found in antifreeze and hydraulic fluids. 

The molecular weight is 76, so the 8.1 mg/dl represents only about 1 mmol/L, however it may explain the severe lactic acidosis and by stimulating the production of D-lactate it may explain even more of the gap.
Kraut, JA
Dialysis removes the parent compound and metabolites. Whether patients need to receive fomepizole is less clear. Kraut and Kurtz suggest fomepizole would be beneficial, while others feel less strongly.

In this N=1 case, our patient did well without receiving fomepizole. 

Thursday, August 13, 2015

#OUWB Questions

This question came in after class from a couple of students.

If the urine sodium in volume depletion and the great edematous states (heart failure, liver failure, and nephrotic syndrome) is low how can the urine osmolality be high?
The osmolality of the urine is made up of electrolytes (sodium, potassium and chloride) and non-electrolytes. The non-electrolytes like urea and ammonia will make up the bulk of the osmolality in the small volume of urine that is seen in this clinical setting.

In the advanced electrolyte class (nephrology and critical are fellowship) we look at the electrolyte content of the urine and use it to look at hypo- and hypernatremia more sophistically. For the purpose of medical school, SHELF exams, and USMLE parts 1, 2, 3 you can safely just look at the osmolality of the urine. We are trying to build a model that is understandable and good enough to predict how patients will behave in health and illness. This works pretty good.

The next question also came from a couple of people in class.

In SIADH, you say that the patients are euvolemic, but then you say they retain water via ADH in the medullary collecting duct. How can both of these be true? Won't they become volume overloaded if they retain water.
This is a common question. The key to understanding this takes a bit of a leap of faith. First off, there is no slight-of-hand here. If you do careful water measurements as patients develop SIADH you can measure an increase in total body water. But critically, the increase in water is not progressive and it does not cause clinically significant volume overload. It does not cause pulmonary edema, it does not cause peripheral edema and it does not cause hypertension, all consequences of true volume overload from a positive sodium balance. 

One of the reasons that excessive water intake does not cause volume overload is that most of that water (two-thirds) disappears into the intracellular compartment. Just like no one complains of their rings not fitting after drinking a lot of water, having high ADH does not cause interstitial edema.

This image from the lecture needs to be front and center when you think about SIADH: water out of balance, sodium in balance:

The last question for now comes from an e-mail (

I had a question from the second half of the lecture about treating euvolemic hyponatremia in the case of adrenal insufficiency. I'm having a hard time understanding why urea and salt tablets would help to reverse the hyponatremia. If solute in = solute out and the kidneys are already in sodium balance, how would it increase the solute load in the case of salt tablets? Even if the urine output goes up, won't there still be non-physiological ADH release and concentration of the urine?
So the best way to think about salt and urea tablets is be visualizing this slide from this SIADH lecture:

In SIADH, the secretion of ADH is fixed and maximal. It's like somone is stepping on the gas and can't remove his foot.

Normally the ADH slides from minimal to maximal in order to balance water excretion with variable water intake:

The ADH slider is supposed to indicate that the ADH can slide from minimal activity, resulting in large volumes of urine, to maximal activity, resulting in minimal urine output. As the questioner correctly intuited, the osmolar load is fully excreted. In euvolemic hyponatremia, the slider is jammed to the right. If the urine osmolality (the denominator) is fixed the only way to adjust the urine volume will be to adjust the osmolar load (the numerator). Increasing the osmolar load with a high protein diet or salt tablets or urea pills will raise the numerator and hence increase the urine volume. It's just math. Yes, taking sodium tablets will just result increase the sodium excretion since these patients are in sodium balance, but this additional sodium excretion increases the urine output making it easier for the patient to have less water intake than excretion, the goal for the treatment of hyponatremia.

Wednesday, August 12, 2015

OUWB School of Medicine materials for 2015

Here is a link to the resources I used last year. They are largely unchanged. The water and solute lecture is available under the lecture tab. I will continue to edit this post with additional materials and links.
  • Solute and Water lecture (Keynote | PDF)
  • Acid-Base lecture (Keynote | PDF)
  • Metabolic alkalosis, potassium and monogenic hypertension (Keynote | PDF)

Tuesday, August 11, 2015

Diuretics, MedMastery, and Keurig

PBFluids has been quiet. Took awhile to just clear the cobwebs to get this post up.

One of the things that has kept me busy has been a project with a company called MedMastery. Franz Wiesbauer was a fan of my fluids book and reached out to me. We worked together to create a curriculum covering body water, diuretics, IV Fluids, sodium and potassium. The full course is about 1,000 slides. But the genius of MedMastery is how they edit and craft the course so it is broken up into an odd fifty 6-minute morsels. It is medical school for Generation Keurig.

MedMastery has opened up a few of the K-cups for promotion. 

Take a look at two of my diuretic lectures:

Some photos from the recording studio

Saturday, June 6, 2015

Reading about Art Levinson in Emperor of All Maladies

Art Levinson is the current Chairman of Apple. He was brought on to the board in 2000 during Job's second act and was present for the introduction of the iPod, iTunes and iPhone.

Art Levinson is always introduced as the former CEO of Genentech but I didn't know his story until I read the Herceptin story in Emperor of All Maladies. Turns out Levinson was trained by Nobel Michael Bishop of oncogene fame. In the late 80's Levinson was leading a group pursuing treatment for breast cancer by doggedly tracking a gene called HER-2.  Genentech's executives turned away from cancer research after some high profile failures in the 80's. This should have been the end of genentech's role in HER-2 except for the leadership of Levinson. He dodged the bureaucracy, pursued resources and lead a small team to continue work on HER-2. The group produced Herceptin, one of the most important breakthroughs in chemotherapy in the molecular era in, a jaw-dropping, 3 years.

Reading that story I can see why Jobs would want him on the Apple board.

Monday, June 1, 2015

Who are "your people"?

As we were gearing up for NephMadness Mealnie Hoenig mentioned that she loved working with the Nephmadness crew because they were "her people." This resonated with me and has become my latest way of looking at the word. This particularly resonated with me when my college roommate introduced me to Public Broadcast Service.

Gene Kranz
There best song is "Go" which samples Gene Kranz dialog with his flight controllers during the Apollo 11 lunar lander landing. I love this because though I have heard the story of the Apollo mission a 100 times I had never thought of it from the perspective of the flight controllers.

This struck me as a great example of my people. While I never could imagine myself as Neil Armstrong, I could imagine me, and my ilk, being a flight controller in Houston. Which one would I be? flight SURGEON, of course.

Summary of the different flight controllers can be found here.

Transcript from the song:

Narrator (NASA Spokesman?)
This is Apollo Control 102 hours into the flight of Apollo 11.
It has grown quite quiet here at Mission Control

A few moments ago Flight Director Gene Krantz requested that everyone sitdown and get prepared for the events that were coming and he closed with the remark "Good luck to all of you." [Ed. not quite One small step for man; one giant leap for Mankind]

12 minutes now until ignition for powered descent. Everything still looking very good at this point

Gene Krantz
Okay all flight controllers, "Go" "No go" for powered descent.
Or if you prefer, the Ed Harris version

Deltcom? [can't quite tell, maybe INCO?]

CAPCOM we are go for powered descent [CAPCOM, capsule communicator, was an astronaut in Houston responsible for communicating with the mission astronauts. At the time of the landing it was Charlie Duke]

We are off to a good start.
Play it cool.

Okay all flight controllers, I'm going around the horn



CAPCOM we are go for landing

Kranz: okay everybody lets hang tight and look for landing radar

Aldrin: 75 feet down a half 
Aldrin: 1202 alarm 
60 seconds [This is the amount of fuel that is left before they must abort]
Transcript of Apollo 11 landing.
CAPCOM: we;re go on that flight
Aldrin: we are go on that alarm?
Aldrin: 40 feet down 2 and a half
GUIDANCE: If it doesn't reoccur we'll be go.
Aldrin: starting second
Armstrong: 1201 
Aldrin: 1201
CAPCOM: Roger 1201 alarm
CAPCOM: Okay, we are go

Aldrin: we've had shut down.
Armstrong: Houston...ah...Tranquility base here. The Eagle has Landed.

Kranz: Okay keep the chatter down in this room. [The greatest moment in the history NASA and Kranz is focused on keeping his team on task]

CAPCOM: T1 standby for T1

Kranz: Stay or no Stay all flight controllers [Apparently it was possible to land on the moon but have something go wrong requiring an immediate return to orbit, so this was a check to see if they could proceed to the lunar surface mission]



Wednesday, May 13, 2015

Goldfarb takes the ACP to the woodshed

David Goldfarb has written a sternly worded letter to the ACP in response to their clinical practice guideline, Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults. The guidelines took positions that seemed to make no sense when looked at as a whole. Due to insufficient evidence the guidelines recommend:

  • no need to determine stone composition prior to treating stones
  • no need to analyze blood chemistry before treating stones
  • no need to do 24-hour (or 48-hour) urine collections before treating stones
What makes those positions so absurd is that if increased fluid intake did not reduce stones the authors suggested a trial of allopurinol, thiazide diuretics or citrate (without guidance on how to dose, follow or how to choose among those therapies). These recommendations are based on research done on patients where the type of stone had been determined. Not following those enrollment criteria makes the conclusions irrelevant.

It is as if the ACP said not to measure blood pressure because there has never been a randomized controlled trial of patients where blood pressure was measured versus patients who do not measure blood pressure.

Goldfarb's letter added some other incredible details to the story I was unaware of including:
None of the authors of the paper have a single other co-authorship in PubMed relevant to kidney stones, other than the AHRQ review. I believe that none of the authors are nephrologists or urologists, none have a kidney stone clinic, none appear at, or present research at, kidney stone meetings, none have any experience regarding management of kidney stones
And this doozy, in response to a comment of the paper from the lead author:

As we point out in the guideline, we are aware that many physicians do select medications based on stone type, for example, allopurinol for uric acid stones, and we do not discourage that practice. 

Physicians who regularly treat stones or who played NephMadness (2014 edition) know that allopurinol is used to prevent calcium stones not uric acid stones which are best treated with alkalinization.

Read Goldfarb's letter. It is excellent.

Calcium Booklet

Minor updates.

PDF (7.6 mb)

Pages (8.7 mb)

I think this covers all the high points that residents need to know about calcium. Please send feedback of what is missing.

Saturday, May 2, 2015

One million

The blog turns 7 on May 30th. But tonight we flipped the odometer.
One million page views.

I bet we never see ten million. Established 2008

The push to one million. Blog post about Twitter (NephJC) and Twitter mention of an old post on MDRD and protein restriction. A PBFluids deep cut.

Friday, May 1, 2015

NephJC: one year in the can

The first NephJC chat was April 29th 2014, so the official birthday went unrecognized a couple of days ago. Such is the way of academic medicine.

Swapnil and I are delighted with the success of the endeavor which launched with humble beginnings on Medium aweek before the first chat with this manifesto:

Coincidental to the calendar turning over, NephJC is being recognized in two articles in the medical literature. The first is the first systematic review of microblogging journal clubs. It is an interesting and thought provoking article. NephJC takes a victory lap in Table 2:

NephJC is third in participants and total number of tweets and first in tweets and impressions per month. I found this paragraph particularly insightful:

Especially in light of Twitter's recent financial results.

The other entry in the medical literosphere was an article written by Swapnil and I as part of a special issue of International Psychiatry Review dedicated to social media and edited by the fabulous Margaret Chisolm. It was a unique opportunity to formalize our thoughts on NephJC and journal clubs in general.

It's been whirlwind first year and I'm looking to see what new boundaries NephJC can stretch in year two.

Sunday, April 26, 2015

Videos for patients and by patients

This is my go to video for helping patients make decisions on what modality to choose.

Last night I received the following Tweet:

I can't recommend the video enough. In this age where everything is sanitized and abstracted as much as possible this video is just authentic. It's as real as it gets. To me it brings to life all of the little things we ask dialysis patients to do, from waking up early, to restricting fluids, to spending 12 hours a week in a recliner hooked up to a machine with only one hand free. 

It is awesome. 

Everyone should watch it.

Canadian Society of Nephrology: Kidney Week's MiniMe

I was invited to speak at the Canadian Society of Nephrology last fall. Swapnil set up a talk on social media. My first international speaking gig. Very cool.

We have two associates out on Maternity leave and another key partner retired a couple of months ago, so practice is tight. No way I could take half a week like I do for Kidney Week. I left for my 1:30 talk at 8:30 that morning. Direct flight from the D to Montreal. As I'm walking through the airport I'm looking for nephrologist ads. During Kidney Week there will always be a big a pharma company advertising in the airport. I love seeing those ads and trying to imagine wha percentage of the general population have any idea what Samsca™ or Aranesp™ are. Montreal had none of these advertisements. I took a taxi to the Hotel Bonaventure.

Found my way to the conference center and registered for the conference. The conference had about 450 people in total, about one 30th the size of Kidney Week. It is like Kidney Week Mini Me. Same clothes, same attitude but smaller. In this case a lot more than just one eighth the size.

Kidney Week is a major international conferences. I heard more foreign languages in Philadelphia last Novemebr than I heard at CSN which was being held in Montreal. We often associate size with quality but thie would be totally unfair to CSN. The lectures were amazing. They absolutly stand toe to toe with the quality you get at Kidney Week. Of course, there are some Canadian specific lectures that didn't interest me, but the general nephrology content was excellent. Five lectures in particular were amazing:

1. Patient oriented symptoms of ESRD

2. Conservative care With Dr. Fliss Murtagh

3. Membranous nephropathy with Daniel Cattran

4. FSGS with Dr. Hladunewich

5. Screening cancer tests in dialysis patients. Dr. Zimmerman gave an excellent and practical talk.

Their were also a few debates. I was disappointed that I had to choose between GN and the hypertension debate. It sounds like it was outstanding:

Swapnil and I did our social media session.


The talk was broadcast live on Periscope. So 21st century.

The plan was a one-two punch, where Sawpnil presented why you should engage with social medi,a and I followed with a "how to" engage in social media. It went well. I had some trouble using Keynote on the iPhone app to advance the slides. I used Keynote on the iPhone to control Keynote on my computer. It worked perfectly during my (admittedly abbreviated) practice sessions and for about half my presentation before it crapped out. I need a more reliable solution, please tweet recommendations. The AV-guy was pretty good at picking up my signals to advance the slides but it wasn't natural and threw my rhythm off. I'm Sorry Canada, I could've done better. That was another difference from ASN. At CSN they had no trouble wiring in my MacBook Air to their AV set-up. Much slicker than the MUST USE POWERPOINT party line from ASN.

I'll post the slides when I get a chance, but first I need to add a slide crediting @Doctor_V and Howard Rheingold, who involuntarily donated ideas to my talk. And I want to pump up the Who to Follow section with a description of mining Symplur to find thought leaders. I also need a slide telling people about Twitter4Nephrons.

In the end, I had a great time at CSN and would definitely go again; maybe not next year in Halifax, but why don't we meet the year after in British Columbia?
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