More merit badges

Another month of consult service and another flight of merit badges:

The first is for the case of rhabdo described in this post.

The second was for a particularly vexing acid-base conundrum that left us all scratching our heads.

And the last was for a diagnosis of Goodpastures Syndrome we made by history and U/A. We found a RBC cast that along with the description of hemoptysis a month prior to admission directed us to the diagnosis. Unfortunately we were too late and unable to salvage any kidney function and the patient now is on dialysis looking for a transplant. When I asked what to do for the badge, my fellow suggested a frowny face.

The badges can be downloaded as a PDF or Pages document and print beautifully on Avery 5163
Shipping Labels

Mystery disease causes kidney failure, or maybe you should just drink more Gatorade

I received this tweet a few days ago:

.@pbjpaulito Did you know about this? http://t.co/ttcnT21GCzcc @kidney_boy
— Meenakshi Budhraja (@gastromom) June 29, 2013

The link goes to this article at the Huffington Post Journal of Medicine and this article from 2012:

The story is about a mystery epidemic causing widespread chronic kidney disease and end-stage renal disease in the farmers of Central America. Here is a less sensational view of the epidemic. The best part of the article is the five paragraphs that quote three independent experts that all agree that the most likely etiology is repeated episodes of dehydration:

“I think that everything points away from pesticides,” said Dr. Catharina Wesseling, an occupational and environmental epidemiologist who also is regional director of the Program on Work, Health and Environment in Central America. “It is too multinational; it is too spread out. 

“I would place my bet on repeated dehydration, acute attacks everyday. That is my bet, my guess, but nothing is proved.” 

Dr. Richard J. Johnson*, a kidney specialist at the University of Colorado, Denver, is working with other researchers investigating the cause of the disease. They too suspect chronic dehydration. “This is a new concept, but there’s some evidence supporting it,” Johnson said. “There are other ways to damage the kidney. Heavy metals, chemicals, toxins have all been considered, but to date there have been no leading candidates to explain what’s going on in Nicaragua… As these possibilities get exhausted, recurrent dehydration is moving up on the list.”

This reasoned diatribe is followed by this:

…scientists have no doubt they are facing something deadly and previously unknown to medicine.

Did the authors even read their own article? Dehydration would hardly be something unknown to medicine. After that, the article really goes off the rails with statements like:

In nations with more developed health systems, the disease that impairs the kidney’s ability to cleanse the blood is diagnosed relatively early and treated with dialysis in medical clinics. In Central America, many of the victims treat themselves at home with a cheaper but less efficient form of dialysis, or go without any dialysis at all.

Newsflash: peritoneal dialysis (the cheaper dialysis that you do at home), is not less efficient than hemodialysis.

The article tips an article that was to be published soon:

Some 30 percent of coastal dwellers had elevated levels of creatinine, strongly suggesting environment rather than agrochemicals was to blame, Brooks, the epidemiologist, said. The study is expected to be published in a peer-reviewed journal in coming weeks.

That article is now available. Here is the primary figure of the article:

masl is meters above sea level
The finding that high altitude is protective is not new, but this study was the first to show it in El Salvador. That is importnat because in El Salvador, sugar cane is harvested at both low altitude and high altitude, so previous findings had been confounded by different crops at the two altitudes.
Also they did some nice work showing a dose response:

It is an interesting story and I am going to keep my ear perked for more information.

Some facts about this CKD epidemic:

  • Men outnumber women 3:1
  • diagnosis typically is in the fourth decade of life
  • Proteinuria is uncommon
  • biopsies have been infrequently done but when available show a tubulointerstitial process with small fibrotic kidneys
  • industries that have high prevalence of disease are:
    • sugarcane cultivation
    • mining
    • fishing
    • shipping
  • Industries with low prevalence
    • coffee growing
    • service sector
  • low altitude has a higher risk than high altitude
Facts from this editorial by DR Brooks in AJKD 2012 59(4)
*Richard Johnson used to hold the Gatorade endowed chair at University of Florida so he should know something about dehydration.

PBFluids in the medical literature

Excellent review of renal on-line learning resources in Advances in Chronic Kidney Disease including a complete round-up of the major kidney blogs: NOD, RFN, eAJKD, and Nephron Power. Here is the description of this blog:

Precious Bodily Fluids (www.pbfluids.com) is a kidney blog by Dr. Joel Topf, a Michigan-based nephrologist who has authored many nephrology-related books. He also lectures extensively on kidney topics for medical students, residents, and fellows. The blog is easy to nav- igate and features links to educational handouts, lectures, and books. The handout study guides are creatively termed ‘‘Haggadah’’ and focus on the basics of acid- base, electrolytes, and acute kidney injury. Handouts are also available on hepatitis-B- and C-related kidney disease, glomerular filtration rate/CKD staging, and rhabdomyolysis. There are accompanying question- and-answer sets with detailed explanations for acid- base and electrolytes for self-assessment. The handouts can be downloaded in a PDF format, PDF booklet format, or a Pages format (which needs special software but can be edited and customized for the individual reader). The lectures section contains 21 lectures on kidney basics as well as other points of interest such as cardiorenal syndrome, uric acid, gout, hypertension, and geriatric CKD, among others. The lectures can be accessed in a PDF or PowerPoint format. In the Books portion of the blog, there are links to books that can be downloaded for free, such as The Fluid, Electrolyte, and Acid-Base Companion; Michigan Hypertension Core Curriculum; and Intensive Care Nephrology. The blog has an archive of posts from previous years and mentions other notable kidney blogs. The user-friendly format of the educational material, complete with befitting images and videos, appeals to readers at different stages of learning.

Flattered.

It’s a nice article, but looking at online education and not even mentioning twitter seems to be skating where the puck is…

Extreme Hypernatremia

Yesterday’s post has stimulated a lot of interesting discussion on Twitter. I have updated the post with some of the tweets. Here are two more that have stimulated some additional thoughts:

@kidney_boy In a case like this would dialysis be better? Or if youre just going to give him free water back, what about a loop diuretic too?
— Matthew Wong (@MatthewLWong) June 11, 2013

@kidney_boy @skepticscalpel This and water poker poisoning incident. Posters for “the dose makes the poison.”
— Casey Lyons (@lyonscas) June 10, 2013

When I was discussing the case with my dad, a surgeon, he kept asking if I would have given a diuretic. I wouldn’t. In fact I wouldn’t have managed the case like the doctors in the case report did.

Now before I express my criticism, it must be noted that the doctors took on a lethal poisoning and undoubtedly saved his life. Criticizing their management may appear to be deducting style points from a walk off home run, who cares if they swung at a bad pitch, they won the game. I want to recognize the bravery, intelligence and success of the medical team but I don’t think it was ideal care and I feel they were just as lucky as they were good.

The crux of their treatment was a massive infusion of D5W. Dextrose infusions are the bedrock of treatment of hypernatremia. The reason is that most routine cases of hypernatremia are due to water deficits:

  • diabetes insipidis
  • dehydration
  • altered mental status
  • disrupted thirst mechanics. 

Outside of treating the side effects of too much sodium bicarbonate (remember the sodium concentration in an amp of sodium bicarbonate is 1,000 mmol/L) we don’t routinely see hypernatremia from salt overdoses.

This patient did not suffer a water deficit, he had salt overdose, a month worth of sodium in a single quart. I think the infusion of 6 liters of D5W in 30 minutes had a high chance of causing serious problems, especially since the patient in question was not volume or water depleted. Not only was he not volume depleted, the high serum sodium was pulling water from the intracellular compartment and shifting it to the interstitial and vascular space,  so not only was he not volume depleted, he likely was volume expanded. The treating doctors took a patient with a lethal sodium ingestion and treated it with a lethal water ingestion (Jennifer Strange who died in the tragic Wee for a Wii incident ingested 7.5 liters over 2 hours).

While in most cases of hypernatremia we give water because that is what is missing, in this case we need to remove the sodium. The treating doctors decided to depend on the kidneys to clear the excess sodium. The kidneys did an admirable job with extremely high urine sodium levels and concentrated urine, however they made that decision while his creatinine was going up. That seems a bit questionable.

The fluid also raised his glucose and lowered his potassium (the D5W infusion dropped the potassium from 5.1 to 2.5 in 30 minutes, I suspect this was an insulin effect). The increased glucose actually blunted the decrease in osmolality that occurred during treatment. In fact if you calculate the osmolality, the infusion of D5W had a surprisingly modest effect on serum osmolality, especially compared to it’s effect on the sodium concentration.

If you do any math on your Mac you stop using the calculator and buy Soulver.

Large change in sodium with 6 liter D5W infusion
Much more modest change in osmolality due to D5W induced hyperglycemia

Again, the treatment worked and perhaps the hyperglycemia helped protect the brain or ameliorated the cerebral desiccation of hypernatremia. I don’t know.

Some may argue that since glucose is not an effective osmole we should not be concerned about it. I think it was an effective osmole do to the lack of insulin activity (evidenced by the high serum glucose). Just like we see cerebral edema from the rapid reduction of glucose in kids being treated for DKA, that is a situation where changes in a normally ineffective osmole cause movement of water.
My dad wanted to use a diuretic because he wanted to get rid of the ingested sodium as fast as possible. The problem with a diuretic is it will decrease the maximum urine concentration so that sodium excretion occurs at a lower urine osmolality increasing urinary water losses, exactly what you don’t want in this situation. The patient was making a large amount of urine and eventually got his urine sodium up to 270 mmol/L and urine osmolality up to nearly 1,000 mOsm/Kg H2O. If he was given furosemide he would not have been able to achieve that degree of efficiency.

I would have been nervous about trying to administer 6 liters of fluid in 30 minutes and assuming dialysis could be arranged to run without delay (impossible in the middle of the night and difficult to assure during the day) I would have selected that option. The reason I like dialysis is that it would remove the toxin, sodium. 
Something that most non-nephrologists don’t recognize about dialysis is that though hemodialysis removes sodium it does not remove it by diffusion, the process by which it removes every other toxin. The dialysate has a sodium concentration that runs from 140 to 150 mmol/L, essentially isotonic. No concentration gradient means no clearance from diffusion. Sodium is removed by ultrafiltration. That means when we remove 4 liters of fluid with dialysis (we essentially use the pumps to squeeze 4 liters of plasma through the membrane’s pores, and those four liters contain isotonic sodium, so 4 liters x 140 mmol/L = 560 mmol of  sodium removed from the body.
In this situation there would some removal of sodium by diffusion because of the extreme hypernatremia and there would be additional removal by ultrafiltration, depending on how much fluid I removed. I would start a D5W infusion at a liter an hour and remove 4 liters of fluid over a four hour treatment. I would check plasma sodium and osmolality every hour and, and, I don’t know how fast I would go:
  1. Should I try to normalize the sodium as fast as possible? 
  2. Should I lower the sodium as fast as possible until the seizing stops and spontaneous movement returns?
  3. Should I lower the sodium at a target rate of 12 mmol/L per hour? 5 mmol/L per hour? 2 mmol/L per hour?
I don’t know but if forced to make a decision I think I would go with answer 2.
How would you manage a sodium of 191?

Saltiest Sodium. Dumbest Dude.

My work-shop on sodium includes a bit on all the cases of hyponatremia due to fraternity hazing.

I also include the crazy case of Jennifer Strange.

But I had never heard of idiot induced hypernatremia until this case report:

A nineteen year old male drank a quart sized bottle of soy sauce on a bet.

Two hours later he was brought to the ER comatose and seizing. His sodium was 177. They initiated hypotonic fluids and arranged transfer to a tertiary care center. At the tertiary care center the sodium was still higher at 191. The doctors then changed the fluids to D5W at 12,000 mL per hour. They gave 6 liters of D5W in 30 minutes.

After the infusion he opened his eyes and regained spontaneous movement. He was discharged on hospital day four neurologically intact with only some minor abnormalities on the head MRI, all attributed to postictal changes.

How high is a sodium of 191? MedCalc will not even accept it as a possible sodium concentration:

A couple items of note:

  • The infusion of D5W raised his serum glucose from 365 (hyperglycemia causes insulin resistance) to 1,116 mg/dL.
  • The authors do not comment on what access they used to infuse D5W at a liter every five minutes.
  • In addition to the hyperglycemia, the D5W infusion dropped the potassium from 5.1 to 2.5 in 30 minutes! That is kind of terrifying.
  • The authors use the Katz correction for hyperglycemia, (eat it Hillier).
  • The authors do not discuss how they decided on 6 liters of D5W. Full correction down to 140 would by roughly 12 liters, so perhaps they decided on 12 liters in an hour with continuous neurologic assessment and when he began to have spontaneous motor movement after 30 minutes they slowed down.

Some nerdery about the sodium exposure: He drank a quart of soy sauce. A quart is 946 mL. The article states that soy sauce is 17-18% sodium chloride. Here are some meta calculations, in case you are interested:

Read the article, it’s a good read and it has the highest urinary sodium I have ever seen, 270 mmol/L (almost twice as salty as normal saline). They discuss other extreme hypernatremic conditions, and theories on rapid or slow correction.

Slides for Keynote | PDF

Update from Twitter:

@kidney_boy I would guess they used a pressure bag or infuser (e.g. Trauma 1) to get in a L every 5 min
— Seth Trueger (@MDaware) June 10, 2013

@mdaware @kidney_boyA good 14 ga 1.75 inch peripheral IV can do 333 cc/min with a 1 meter pressure head to gravity.
— philroman (@philroman) June 11, 2013

@kidney_boy I’ve seen 216 before. Started at 196, rose more with initial NS administration. Kid with ichthyosis, and bad dehydration.
— Ken Tegtmeyer (@pccm_doc) June 11, 2013

July first approacheth

I wrote a post for the Pediatric Career blog. It is about July first, the most significant date in the academic medicine calendar. I did not discuss patient risk or medical mistakes. I have blogged about those before. I discussed how to leverage this new beginning to develop a fulfilling and productive career in medicine. Read it.

Medicine, 4 log units above normal!

Highest CPK I have ever seen:

That is the first CPK over one million I have seen. I love how the CPK of 4,000 on day one, you know the CPK that is 20x the upper limit of normal, is not high enough to even be rendered on the graph. For the scientific-minded here is the same data on a log rhythmic scale:

We were able to successfully alkalinize the urine (EBM purists can bite me, I  believe the bench data here) and she never became oliguric, however on day three her potassium was 7 and we initiated dialysis. Surprisingly, phosphorous never got out of control.

She also had the highest CRP I have ever seen, 147.

The etiology you ask? She presented three days after a sore throat. We initially discounted viral rhabdo because the CPKs were so high but the Coxsackie B type 3 and 4 antibodies were off the scale and the literature is sprinkled with similar case reports (here and here). Muscle biopsy results are pending.

Muddy brown cast (day one, unspun specimen):

Urine sample (day two with urine pH of 8.5), no red cell on U/A

Still can’t believe I didn’t get a picture of the urine on the first day, it was black.

.@kidney_boy re:CPK I see Phos was never uncontrolled – anything to say about Ca both at presentation & during alkalinisation? #nephrology
— Tom Oates (@toates_19) June 4, 2013

See this:

Best post I have read on how to pay donors for kidneys

If you want to start a fight among nephrologists, start talking about paying donors for their kidneys. This may be the most contentious issue in nephrology. I personally am a believer in the concept but trying to imagine a free market for organs makes me nauseous.

Rohin Dhar, at the Priceonomics Blog has put together a brilliant, straight-forward essay describing the problem, showing how current ideas for increasing the organ supply (make donating organs the default after death, paired kidney donation, improved donor-recipient matching) are not working and cannot hope to solve the problem and then goes on to describe a hypothetical organ purchasing system run by medicare. I’m convinced.
When discussing this on twitter, the always interesting Christos Argyropoulos talked a bit about the problem with Greece’s implementation of default organ donation:

@kidney_boy The Iranian system was covered last year in KI if I am not mistaken. Opt out can also backfire as it has in Greece
— ChristosArgyropoulos (@ChristosArgyrop) May 29, 2013

@kidney_boy Opt out legislated in 2011;hugely unpopular, a couple of high profile resignations from the Ntl Transplant body-> # of Txps down
— ChristosArgyropoulos (@ChristosArgyrop) May 29, 2013

@kidney_boy Public pushback makes ICUs reluctant to refer donors,even though almost everyone is. Opt out systems are embraced not imposed
— ChristosArgyropoulos (@ChristosArgyrop) May 29, 2013

An open access review of Iran’s transplant system can be found here (A non-systemic review from McGuil University? I grow feint.) Here is the Kidney International paper Dr. Argyropoulos was referring to.
Look at how the number of transplantations is growing in Iran:
Mitra Mahdavi-Mazdeh. Kidney International, 2012
While it is flat in the US:

USRDS

The current system of paired exchanges and campaigns for kidney donors has noble intentions, but it’s not working. People are needlessly dying as a result.