Tuesday, April 30, 2013

NephMadness: The Final Post

We posted a final wrap of NephMadness at eAJKD. I filled out my brackets on March 21st, right before we revealed the field of 32 but I didn't post them because of my involvement with the tournament.

Dancing with my brackets.
No I'm not a loser.
Why do you ask?

As promised here are my brackets:

Notes from Glomerulus Region:
  • DOPPS over USRDS: I feel the we have more to learn by looking outside of the US than looking in the mirror
  • Propensity scoring to the Sweet 16: We should demand it in all observational trials of therapy. We need to get better at finding the truth from these observational studies
Notes from the Proximal Tubule region:
  • TREAT is one of the most important trials in nephrology because finally after 25 years someone finally did the placebo controlled trial of ESA that we should of had in the 90's. It is never too late to do the right thing.
  • ALLHAT is not all that.
  • FGF23 is not important because of how it was effective as a prognostic tool, but because it is a new hormone that regulates phosphorous. How cool is that? It reminds me that no matter how authoritative the text books are when they describe human physiology they are all vulnerable to advances in science.

Notes from the Loop of Henle Region:
  • I think anyone that heard the first hand accounts of using Eculizumab for the 2011 outbreak of atypical HUS in Germany would vote for it. The stories are incredible.
  • UpToDate to the Final Four. What can I say, I have a crush on Bud Rose. He should get the Nobel Prize in Medicine for what he has done for medical education and delivering advances in medicine to doctors treating patients.

My final four was very conventional and of course Transplant for the win.

Thursday, April 25, 2013

DCIS = Gleason 6 = CKD 3

Today I read the excellent NYT Magazine story on breast cancer

The entire article is great and I recommend it but one aspect of the story was the rise of ductal carcinoma in situ. Here is how it is described:
Many of those women are told they have something called ductal carcinoma in situ (D.C.I.S.), or “Stage Zero” cancer, in which abnormal cells are found in the lining of the milk-producing ducts. Before universal screening, D.C.I.S. was rare. Now D.C.I.S. and the less common lobular carcinoma in situ account for about a quarter of new breast-cancer cases — some 60,000 a year. In situ cancers are more prevalent among women in their 40s. By 2020, according to the National Institutes of Health’s estimate, more than one million American women will be living with a D.C.I.S. diagnosis.

D.C.I.S. survivors are celebrated at pink-ribbon events as triumphs of early detection: theirs was an easily treatable disease with a nearly 100 percent 10-year survival rate. The thing is, in most cases (estimates vary widely between 50 and 80 percent) D.C.I.S. will stay right where it is — “in situ” means “in place.” Unless it develops into invasive cancer, D.C.I.S. lacks the capacity to spread beyond the breast, so it will not become lethal. Autopsies have shown that as many as 14 percent of women who died of something other than breast cancer unknowingly had D.C.I.S.
The point is, our diagnostic technologies have found a "pre-disease" state and we now take credit for curing these people when they may never have developed the lethal form of the disease. A conversation on twitter erupted regarding D.C.I.S. and its equivalence in prostate cancer, another disease mired in controversy regarding diagnostics and the benefit of early diagnosis.

Their is, in fact, a movement to re-name Gleason 6 tumors that avoids the term cancer as a way of emphasizing the low aggressivness of the condition:

Here it is in all its PDF glory
In the absence of definitive markers of the lethal phenotype, a new paradigm is needed to express the risk associated with Gleason score 6 tumors. We propose to adopt at Johns Hopkins an alternative approach based on a modified Gleason scoring system referred to as prognostic grade group. Five prognostic categories will be reported based on prostate biopsy (Table 1). For men undergoing radical prostatectomy from 2004 to 2011, these prognostic grade groups from 1 to 5 have been associated with 5-year biochemical recurrence-free survivals of 94.6%, 82.7%, 65.1%, 63.1%, and 34.5%, respectively (Pierorazio et al, manuscriptin preparation).

This made me think, what is the DCIS or Gleason 6 of nephrology, and I think by far its CKD stage 3. New patients that are referred to me come in to the office with labs results in hand. They frequently have seen information on line or in posters that explain that their eGFR of 52 mL/min is CKD stage three and they see that Stage 5 is dialysis. So they come to two conclusions:

  1. They are going to be on dialysis soon
  2. Why didn't anyone ever warn them when they CKD stage 1 or 2?
The problem with using numbers to stage a condition is people reasonably expect a stepwise progression from stage 1 through stage 5. The reality is, if they have normal kidneys on U/S and a normal urinalysis, by far the most common situation, they have no kidney disease when their eGFR is greater than or equal to 60 and jumps to stage when their GFR falls below 60. Absurd. Additionally only 1% of stage 3 patient progress to dialysis.
From my GFR handout
I am excited to see how the KDIGO guidelines and their heat map of GFR + Albuminuria perform as prognostic guides, but I would have been happier, if they had renamed CKD 3 as CKD stage 1 and using CKD stage 0 for GFRs greater than 60 ml/min plus evidence of renal disease. 

Update from Twitter (where else?)
Amyloid_Planet: Nice blog post today BTW - bit off a lot with that one.

Kidney_boy: What? You think taking on Komen, the urologists'
 cash cow and K/DOQI is a big post?

Amyloid_Planet: Potentially controversial, yes. I'm surprised you didn't take a shot at Jesus while you were at it.

Kidney_boy: follow-up post

Wednesday, April 24, 2013

HIV renal disease

I gave a lecture on HIV renal disease to the ID section yesterday. I give this lecture every couple of years. I swear that lecture changes more from year to year than any subject I talk about.

  • The lecture was about one hour. 
  • The section on APOL1 is rough.
  • I would like a slide describing the transgenic mouse model studies by Klotman that showed that transcription of nef and pol are central to the disease.
  • I need some notes on why I have 2 graphs on slide 16.
  • Add some highlights to table in slide 23.
  • Loved how slide 26 and 27 worked.
  • I think there might be better data on steroids in HIV. Slide 51.
  • Need to flush out IRIS and DILS from slide 67
  • Add comment on adefovir slide mentioning that the hep B dose is a sixth of the anti-HIV dose


Monday, April 22, 2013

Dialyzing the highest potassium

So last week I asked how you would dialyze the patient in the following scenario:
You have been called on a Sunday night for emergent dialysis in a patient with hyperkalemia. The patient is a MWF dialysis patient and had a normal dialysis session on Friday. Her ECG on admission is absolutely terrifying and her potassium is 9.9 (hemolyzed). The blood sugar on admission was 965. When you arrive, with K-machine in tow, the patient has been on an insulin drip for an hour and the potassium is down to 5.2
I have received 54 responces and the results have been pretty stable from the beginning. By far the favorite option was to pack up the dialysis machine and head back home. No dialysis for you

I don't see any signifigant trends based on background of the provider:

The raw data is available for perusal here. And you can keep voting here.

That is not how I voted. I voted for 2 hours on a 2K bath. My feeling was that the ECG showed dramatic cardiac toxicity and though the emergency seemed to be over, with a repeat potassium of 5.2, I had no guarantee the insulin drip would continue through the night. If it was stopped, intracellular potassium could diffuse back out of the cells. But what really pushed me was the fact that he is scheduled to receive dialysis in just a handful of hours anyways. If I just push that schedule up and dialyze him tonight I provide an extra margin of safety for his potassium and improve my sleep hygiene. No nightmares of lost IV access for the insulin drip.

Because I viewed this emergency dialysis as just pushing forward the scheduled dialysis I went with the standard 2K dialysis bath.

Now for the best part of any blog post, belittling people who don't agree with me. The above paragraph takes care of no dialysis.
  • Zero K bath. Too great a risk of hypokalemia. We presume that he does not have excess total body potassium, merely maldistribution of intracellular potassium. Zero K baths are dangerous. Who can forget the classic scene in Grey Anatomy where Izzie is fired for ordering a zero K bath, putting a patient in shock, so that the poor dialysis patient misses her transplant. (I love that show, they even let surgical residents write dialysis orders.)
  • One K bath. See above. Though the concern about the toxicity of low potassium baths seems to be overblown.
  • Two K bath. Perfect.
  • Three K bath. Should work just fine.
  • Four K bath. What's the point, at the current potassium of 5.2, two hours on a 4 K bath will remove a trivial amount of potassium and is functionally identical to no dialysis at all.
Defend your sorry choice in the comments below.

Wondering if my fluids book is worth reading?

The fluids book is certainly priced right (free) but if you need an additional endorsement, Richard Sterns, the Dean of Sodium, uses figures from the book in his talk at the ASN board review class!

From Edgar Lerma.

Update: got this e-mail the other day:

Hello from the blogosphere

One of my colleagues pointed me to your website today.  I don’t know that you’re right about me being the “Dean” of anything, but you are correct:  I loved your book.  Hope you don’t mind that I borrowed from it.


Richard H. Sterns, MD
Chief of Medicine
Rochester General Hospital
1425 Portland Avenue

How fun!

Friday, April 19, 2013

There once a dialysis patient from Nantucket...

My son is doing a big project on the kidney. As part of that project he has to write a limerick about the kidney. The family was stumped so of course we decided to crowd source the problem:

The answer was analysis and paralysis (hat tip to @emmadalton and Leon)

But the real fun began as people sharpened there pen knives and carved new limerick's on to the bathroom walls of twitter.

Daughter noted spelling error (now instead of know)

Daughter wrote that one.

My son is pretty independent and ignored all of the bad poetry advice on Twitter and went with this original creation:
There once was a kidney named Bud
He liked to filter the blood
He got a disease
There's pus when he pees
And now Bud is simply a dud

Wednesday, April 17, 2013

Was #NephMadness the biggest MedEd Social Media campaign ever?

I am going to write a wrap-up of NephMadness for eAJKD. As I'm thinking about this the following sentence springs to mind:
NephMadness was the biggest medical education social media campaign, not tied to a conference, ever pulled off.
Am I being an ass or is that right?

Are there even any other MedEd social media campaigns not tied to a conference?

The only one I can think of is #overlyhonestmethods

What other events should it be compared to?

Keep in mind this was a coordinated campaign involving one central blog but generated posts on at least four other blogs, had a single Twitter account but ultimately had 75 people on Twitter using the hashtag.

I really would appreciate any thoughts about this. Please tweet @Kidney_boy or fill in the comments below.

Tuesday, April 16, 2013

I did this interview for eAJKD. I met Jamie Dwyer once, and though he was charming, well spoken and clearly intelligent the overriding biggest impression was that he was best dressed nephrologist I ever met.

Hyperkalemia, medical management

The highest potassium I have ever seen is 9.9 mmol/L...

...however, it was a hemolyzed specimen so it is a tarnished victory. The patient is a dialysis patient in DKA and had a blood sugar of 925 at the time of the hyperkalemia.

I love that the only things not circled are a creatinine of 8.9 and BUN of 50.
The patient was started on an insulin drip and one hour later his potassium was 5.2 mmol/L. A drop in the serum potassium of 4.7 mmol/L is profound and atypical. This is due to two factors:
  1. The initial serum potassium was not that high, despite the subtle EKG changes the real potassium had to be somewhat lower and falsely elevated due to the hemolysis.
  2. In DKA the hyperkalemia seen on presentation is due to a transcellular shift of potassium from the lack of insulin and increased extracellular osmolality (from the hyperglycemia), both of these are quickly reversible with IV insulin.
Adrogue et al created a formula to predict the potassium at admission in DKA.

K+= 25.4 – (3.02 x pH) + (0.001 x glucose) + (0.028 x Anion Gap)
The calculation is a totally failure in our patient: it comes to a predicted potassium of 5.6. Though the equation is not very predictive (R2= 0.25), the article does a nice job reviewing the mechanisms of hyperkalemia in DKA. This is a concept that is commonly misunderstood. Medical students are quick to rely on the mechanism of potassium moving out of cells in exchange for hydrogen moving into cells in the face of acidemia. Adrogue reviews the data that shows that this does not occur with the organic acids of DKA or lactic acidosis but that acidemia does inhibit the Na-K-ATPase.
Nice picture but this in not an important mechanism in the hyperkalemia of DKA.
The reason that acidemia does not generate hyperkalemia in DKA, is that the anions move into the cells along with the hydrogen ions, so there is no need to excrete potassium to maintain electroneutrality.
Horacio E Adrogue
Funny story about Adrogue, I was eating breakfast at Kidney Week in 2011 when I looked at the name tag of the guy sitting next to me, it was Horacio Adrogue! My chin hit the floor and I started to gush about how much I respected his work and how I loved his NEJM electrolyte reviews and how I was hoping he would autograph my chest and could I pick up his dry cleaning and... then he interrupted me to explain that he was not the Adrogue I was looking for. He was, in fact, The Man's son and a transplant nephrologist of some regard. How humiliating. 
A nice review of the hyperkalemia and hyperglycemia in dialysis patients was published a couple of years ago by Tzamaloukas, a widely published investigator on the subject. I love this figure from the review which shows a curvilinear relationship of glucose and potassium in dialysis patients.

Nice graph except for micromoles of potassium
per mmol of glucose. Really? Could you make
it more obtuse?
One of the interesting conclusions that I learned from the review: one of the most important variables which affects how much the potassium will fall with insulin is the pre-treatments potassium level, the higher the potassium, the greater the response to insulin. The data from that conclusion  comes from this study: Serum potassium and acid-base parameters in severe dialysis-associated hyperglycemia treated with insulin therapy. It is an analysis of 43 episodes of hyperglycemia, half DKA and half non-ketotic hyperglycemia. Here is the money shot showing the relationship to initial potassium to drop in potassium:

What would you do for this patient? 

I will share the results in a week or so.

Addendum: some of the funnier tweets in response to my original tweet:

We loved that comment so much we made it the Hyperkalemia Merit Badge:

But maybe we should have used:

Monday, April 15, 2013

Rules of Stone. Updated.

William J Stone is Chief of Nephrology at the Tennessee Valley VA and faculty at Vanderbilt Medical School. He discovered beta-2 microglobulin amyloidosis in long term dialysis patients. He describes the discovery here:

I discovered B2M amyloid in 2 hemodialysis patients during the late 1970’s and early 1980’s who sequentially broke both femoral necks. We were doing home hemodialysis on 75 VA patients, who lived an average of 220 miles away. One of them had a cystic knee lesion, which we biopsied. It was Congo red positive. A light bulb went off in my brain. All of the femoral neck tissue from both patients at joint replacement, misread as increased connective tissue, was full of amyloid. Workup for AA and AL was negative. The patient later died of lung cancer. At autopsy we scooped the amyloid out of a large humeral lesion. When sequenced in NYC, its subunit was intact B2M. To my knowledge, this has not been repeated.
In the early days of dialysis he was in Vietnam with Army and used dialysis for battlefield injuries, Stone again:
I was sent to the Third Field Hospital in Saigon from 1968-69, where we dialyzed battle casualties and falciparum malaria cases of AKI. I had completed a basic science nephrology fellowship at Cornell from 1965-67 and had never done dialysis before. We saved a lot of them using the old coil dialyzers.
One of his former fellows described him as, "One of those guys who can describe a case of almost anything you can imagine, across all of internal medicine."

Dr. Stone has created the Rules of Stone, bits of wisdom that should guide doctors through the uncertainties of diagnosis and treatment.

Rules of Stone

  1. Anything can do anything. (WJS clarified: is for people who say things like a stroke alone cannot give you a high fever)
  2. Anything can do nothing. (WJS clarified: is for those doubters who say a patient on prednisone will have a tender abdomen if he has perforated an ulcer or a diverticulum)
  3. Nothing can do anything. (WJS clarified: refers to self-inflicted illness; e.g. IV injectors of dissolved pain pills can have multisystem disease)
  4. Nothing works every time.
  5. No lab or diagnostic test is perfect.
  6. No disease is always predictable.
  7. Just because you can do something doesn't mean you should do something.
  8. A patient known to have x,y, and z doesn't necessarily have x, y, and z.
  9. A person with an illness similar to a previous one probably has it again.
  10. No list is complete.
  11. The more drugs there are for a disease the less likely they are to benefit it.
  12. There are no uninteresting patients (just disinterested physicians).
  13. Four drugs are more toxic then two.
  14. Always guess 20% if you don't know the real answer.
  15. No drug has been proven useless until it has been tried in scleroderma and ALS.
  16. Just because you failed to diagnose the cause of X in the past doesn't mean you shouldn't try again.
  17. Orneriness is best treated as an outpatient.
  18. If an older doctor writes an axiom or a diagram on a piece of paper, ask if you can have it.
  19. Common but unrelated diseases co-exist at least 1% of the time.
  20. If asked when you last played basketball, be able to answer with a day of the week.
  21. Before addressing non-compliance with diet and medicine #1, doctors add medicine #2.
  22. In a sick patient without a diagnosis, get invasive early.
  23. You cannot learn medicine at home, so the new residency hours rules make no sense. A cadre of doctors with inadequate experience is being created.
Two notes
  1. I am in total agreement with #23 
  2. The best safety data on creatine come from long term (negative) trials on using creatine in ALS, #15.

Saturday, April 13, 2013


Hyperglycemia causes pseudohyponatremia. The sodium is diluted by the osmotic movement of water from the intracellular to the extracellular compartment. I was taught the Katz conversion to correct the sodium, the sodium falls 1.6 mmol/L for every 100 the glucose is over 100. This comes from purely theoretical work and was published in a letter the NEJM in 1972.

In the 1999 Hillier et al published empiric data that showed the ratio to be 2.4 rather than 1.6.

This ratio is now has been adopted by Mass General Handbook of Internal Medicine.

When ever I encounter hypernatremia I use both formulas and I consistently found that the Hillier estimate overshot the final sodium. I wanted to do a study where I looked at hyperglycemia in dialysis patients and measured estimated final sodium versus actual final sodium to see which calculation worked better. It is a good study cohort because the lack of urine output guards against renal losses a potential source of error. Well, the study has been done. Tzamaloukas et al, published a nice study of hyperglycemic dialysis patients and found the ratio of change in glucose to change in sodium was to be 100:1.5, almost exactly the same as Katz's calculation and consistant with my experience.

The y-axis is the Katz estimate minus the actual final sodium. so a perfect estimate is zero. The x-axis is the average of the Katz and actual final sodium. The Katz conversion work well across a range of actual sodium levels.

Eat it Hillier.

Update, Dr. Rondon, in a comment below and Martijn vd Hoogen on Twitter, believe that I made a mistake calling hyperglycemic hyponatremia, an example of Pseudohyponatremia. There is some precedent for this position but it is not universal. See this editorial by the American Association for Clinical Chemistry, or McGraw Hill Concise Dictionary of Modern Medicine

We care about the serum sodium because of its effect on serum tonicity. When the serum sodium doesn't represent the serum tonicity, the sodium is lying, I call that pseudohyponatremia. Pseudohyponatremia comes in two varieties: normal osmolality and high osmolality. The high version is what I am talking about in this post, the low version is what Drs. Rondon and Martijn vd Hoogen are referring to in there comments/tweets. More information on that can be found here.

Wednesday, April 10, 2013

iPhone urine micrographs

Calcium oxalate crystals
dirty granular casts indicative of ATN in a field of hematuria.
(The top left corner of the longer cast looks a little red cell cast-like)

Broad waxy cast, indicative of chronic kidney disease in a field of RBCs

New Nephrology merit badge for successfully using your iPhone to make a urine micrograph.

How do you determine the severity of SIADH? Updated with Video

There are a number of ways to grade the severity of SIADH. The most obvious is to look at how low the sodium is. The problem with this is that it largely depends on how much water a patient is drinking and is not solely dependent on the severity of the SIADH. A patient with mild SIADH that is started on hypotonic fluids will have a much lower sodium than a patient with severe hyponatremia who is adherent with her water restriction and urea tablets.

I assess the severity of SIADH by looking at the electrolyte content of the urine. Here is a doozy:

  • Urine sodium: 134
  • Urine Potassium: 62
  • Urine osmolality: 777
But this strategy suffers from a similar limitation, the urine electrolyte are affected by factors beyond the severity of the SIADH. Patients with SIADH are in sodium balance, that means that all the sodium they ingest is excreted. Increased sodium intake will be reflected by increased urine sodium, the same goes for dietary potassium and urinary potassium. The above labs came after the patient was given isotonic saline for 24-hours. The serum sodium fell from 128 to 117 with saline.

The true measure of SIADH severity probably is simply the urine osmolality.

Monday, April 8, 2013

Creatine is not just Creatinine misspelled

A few years ago I had a pre-med student shadow me on the dialysis service for a week or two. I had a hard time teaching him because he was so early in his medical education. I had him investigate an issue that he had some personal contact with and I think he did a nice job. The question was, "Is creatine nephrotoxic (bad for the kidneys)."

From this commercial sight, their
information is pretty tight
Creatine is synthesized by the body from the amino acids arginine, glycine, and methionine. It is phosphorylated by ATP to form phosphocreatine which is stored in muscle cells and acts as an instant energy source. When exercise depletes ATP, phosphocreatine rapidly restores ATP from ADP. Skeletal muscles typically have 3 times as much phosphocreatine as ATP. After being used up creatine is excreted as creatinine (and you thought creatinine's purpose was to measure renal function).

The student, DJ_Scary, put together the following presentation on the biology and nephrotoxicity of creatine.

Medicine tends to be pretty puritanical. If it feels good, don't do it. If it it feels bad, do it more. Eat your vegetables. Exercise every day. Don't drink. Don't smoke, Eat less red meat. Don't put so much salt on your food. When it comes to performance enhancing drugs, the knee jerk and conservative response is the same. Avoid protein supplements. Don't use anabolic steroids. Creatine will damage your kidneys. Some of this advice is wise, Joshua Schwimmer showed that anabolic steroids can cause FSGS (anybody ever test Zo or Sean Elliott for steroids?).

Creatine can double, triple or quadruple a patients serum creatinine. The math on how that works is shown in the video.
Note for the equations to be valid the following assumptions and units need to be used:
  • CrCl: ml/min
  • Creatinine: mg per 24 hours
  • Serum creatinine: mg/dL

The point of the video is that creatine will increase your creatinine and not affect your creatinine clearance or GFR which are the important variables. This is a situation where one cannot trust the estimated GFR formulas.

The medical puritan tells patients not to use creatinine because it can damage the kidney. This is not true. There is no data, beyond some pretty sketchy case reports that creatine can damage the kidney. Long term follow up with medical use of creatine shows no harm (randomized, placebo controlled data!). It seem convincingly safe (Oh, you wanted a Cochrane Meta analysis, we got that here). It will always be safer and more conservative for physicians to tell patients not to take a substance. (One year follow-up too short for you, how does 5 years of follow-up taste?) Patients deserve honest, unbiased answers about what different substances and behaviors do to their bodies and if physicians provide them with the same, old, predictable, puritan, advise, they will bypass doctors and we will lose our role in health advice.

To see a range of nephrologist views on creatine, take a look at the replies to this tweet.

Friday, April 5, 2013

NephMadness Twitter Analytics

Symplur.com is such a treasure. Here are their analytics for the NephMadness hashtag.

Make sure you vote for the champion from the final four.
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