musings of a salt whisperer
I go slow when replacing potassium. I mean, they do use that stuff to execute people.
Jason Ye- orthopedic surgery intern
via Chinita Furiosa
Must read post about a recent Lancet paper comparing outcomes for patient treated for health care associated pneumonia (HCAP) and looked at outcomes based on adhering or non-adhering to the ATS and IDSA guidelines.
Spoiler alert: patients treated off guidelines did better.
I grabbed dinner with Matt Sparks, one of the driving forces behind the Renal Fellow Network. It was a great dinner and, for me, was the first time I had a chance to talk shop with another blogger. Very fun. One of the things we discussed was the role of blogs in fellow education (this idea was matured a little with a discussion with Conal O’ Seaghdha, the other half of inspiration that drives RFN.
I believe that the primary educational material for medical education has gone through three phases. In the beginning was the medical text book. This was exemplified by Harrisons which rose to ascendancy not by being the first text book but by being the most innovative. Harrison unique innovation was arranging the sections by patient complaint rather than by disease. Here it is described in a fascinating history of the Harrison family of doctors:
PRINCIPLES OF INTERNAL MEDICINE would offer medical students a new way of approaching patients. The Cecil Textbook of Medicine, which had previously monopolized the American medical textbook market, took a less helpful approach. Its author, Russell Cecil, M.D., of Cornell Medical School in New York, had organized the textbook exclusively by disease, offering the definition, cause, symptoms and signs, methods of diagnosis, treatment, and prognosis for each one. This meant, of course, that a student must identify the patient’s disease before the book would offer help. Principles of Internal Medicine, on the other hand, began with the patient. Tinsley [Harrison] devoted the first third of his textbook to symptoms and signs experienced by sick people, which included shortness of breath, swelling of the feet, and so on-leading from there to understanding the disease. The text mirrored the ideal practice of a physician. The first edition of his book, published in 1950, proved an instant and major success.
The second phase was UpToDate. Burton “Bud” Rose (how can Wikipedia not have an entry on Dr. Rose?) crushed the primary medical references by creating a comprehensive, readable and searchable reference. He also cajoled his authors to make specific treatment recommendations so Up-To-Date is the only medical reference that actually teaches you to take care of patients. One of my friends used to complain that when she would invest the hours and tears needed to read a chapter of Harrison’s she would finish with tremendous knowledge and the ability to shine on atending rounds but have no idea how to treat her patient. UpToDate is not like that and has probably saved more lives than ACLS. I routinely ask prospective fellows about their reference of choice and for three years running every single one of them has answered “UpToDate.”
As good as UpToDate is it has some weaknesses. The EBM zealots take it to task for relying on expert opinion but I really don’t have too much concern about that (my previous post on that took them to task for saying they are EBM when they are really an expert opinion source. That’s why the list of author/editors is so important and impressive. They should be proud of what they are rather than claim to be EBM) .
What concerns me is UpToDate’s inability to escape its CD-ROM DNA. I have been a subscriber to UpToDate since I was a resident and Burton Rose was still answering the phone to deal with bad CDs and pimping the still incomplete product in the hallways of Renal Week. The ascendancy of the Internet has allowed UpToDate to get out of the CD shipping business but they still refuse to link out even when it makes overwhelming sense. All of their articles are fully referenced, but not with links to the primary data or the pubmed reference but to an internal database record of the reference.
It feels that the editorial rules for UpToDate were created in the CD-ROM era of the 90’s and haven’t been updated for the internet era.
I beleive that, just as Harrison had an openning in the Internal Medicine textbook space by using patient oriented complaints to organize his text and Rose had an openning by using search and a unique editorial style, the technology of today provides a niche. I want an interactive textbook of medicine with comments, a Facebook “Like” button, a way to connect with other practitioners and share treatment pearls.
The renal fellow network and other knowledge focused medical blogs are early progenitors of this future but some pretty large problems need to be addressed:
– Posted using BlogPress from my iPad
Last week I posted on my pregnant patient who has Gitelman’s Syndrome. I am managing her with amiloride and a mixture of oral potassium and a mixture of oral and IV magnesium.
I received the following letter from a reader who went through a similar experience:
I am not a doctor, but I have Gitelman’s, and 16 years ago, was pregnant and ended up having to go on amiloride at the start of my second trimester, because my potassium and magnesium levels just tanked. Being part of proving the track record on the viability of amiloride in pregnancy was a scary time, I tell you what. Your patient’s experiences are similar to mine, though I did not require the magnesium IVs she apparently does during gestation.
The great news is my son turned out healthy, and without any sign of potassium disorders of any sort, so far as we can tell at nearly 16. He’s healthy, bright, nearly 6 ft – no indication at this time that he was harmed in any way by the fetal exposure to amiloride.
And another point to pass along – after he was born, I had my breast milk checked for traces of amiloride, and it passed whatever screens were applied. Therefore I nursed him for about 9 months, though I supplemented with formula. It was an acceptable risk for me – since I know the literature does not record any data on nursing while on amiloride, I thought I’d pass along one uncontrolled anecdote for you to ponder. [Note: on further communication the patient clarified that she did not take amiloride during breast feeding]
Anyway, please pass this information along to your patient – I am sure it will help her peace of mind to know another successful long term outcome. It was a scary time for me, and without the widespread use of Internet back in 1995, the only piece of mind I got was by tracking down Dr. Almeida, who wrote the 1989 paper about Gitelman’s in pregnancy. I spoke to one of his nurses to see if they could give me some info on long term followup on the baby, but the mother had disappeared after giving birth, and they had nothing to report.
Best of luck to your patient – I know what she’s going through.
Final note for your patient going forward: Getting my levels back up after the birth was a bit of a challenge, I recall. But many of the details have been lost to time and the fog of war, I’m afraid – I will just say that the first month post-partum was pretty rough on me.
The Renal Fellow network may have ranked APOL1 as the fourth biggest story of 2010 but I think it is actually the best story in all of medicine, not just nephrology.
When I went to ASN Renal Week I stayed at Castle Marne, an idiosynchratic bed and breakfast about a mile and a half from the conference center. The other people staying at the Castle were a rogues gallery of interesting conference participants.
One of the breakfast crew was David J. Friedman, the second author on the Science paper blowing the lid off of APOL1.
 |
| Data from USRDS and US Census |
 |
| The NIH and NIDDK sponsored symposia to get scientists up to speed with breakthrough discovery |
A limitation of our study is that we have not yet identified the causal sequence variation in MYH9 that is associated with FSGS
Then in August 2010, David Friedman and his team identified APOL1 as the gene that actually was associated with FSGS, HA-ESRD and HIVAN. The association was discovered after new genetic material was made available in the 1000 Genomes Project, a public database of genetic information from individuals around the world including a number of Africans.
APOL1 lives just to the centromere side of MYH9. Friedman et al showed a tighter association with APOL1 than MYH9 and when they controlled for APOL1, MYH9 was no longer significantly associated with renal disease.
As the scientific community began to feel the rumbles of truth emerge about MYH9 and APOL1, researchers hitching their wagon to MYH9, prayed they were funded before the NIH scorers realized that MYH9 was the wrong gene. Scientists with research proposals on MYH9 that were too late would have to rewrite the grant to focus on the new target, APOL1.
Friedman’s team didn’t just identify APOL1 they told a fascinating story involving parasitology, evolution and human migration.
In 2003 APOL1 was identified as the genetic source for an immunity factor which protected people from African sleeping sickness. 95% of African sleeping sickness (I refuse to use the 3-letter acronym) is caused by Trypanosoma brucei gambiense.
Trypanosome lytic factor (TLF) protected humans from sleeping sickness until Trypanosoma brucei rhodesiense and gambiense evolved a protein, Serum Resistance Associate Protein, that deactivated TLF. This adaoptive response by the trypanosome made humans susceptible to infection. This was the state until about 10,000 years ago when variants of APOL1 appeared and restored the protective action of TLF and made the carrier of even a single copy immune to African sleeping sickness.
These genetic variants of APOL1 appeared in Africa 10,000 years ago, but much of the human race had already left Africa to spread across six continents. Additionally, regions that did not have the Tze Tze fly didn’t have trypanosomes and hence didn’t have selective pressure for the APOL1 variants. In regions endemic to Tze Tze fly, the selective pressure for these mutations was immense. In the U.S. 30% of African Americans carry APOL1. Heterozygotes are immune to trypanosomes and may have a modest increase in the risk of HA-ESRD (OR 1.26, no risk for FSGS) . Homozygotes for APOL1 are equally immune to trypanosomes but unluckily have a sky high risk of renal disease.
So APOL1 behaves like sickle cell anemia and malaria. Heterozygotes are immune but homozygotes suffer from devastating disease. Balanced polymorphism.
The last twist is the mystery of HIVAN in Africa. HIVAN is found in western, Sub-Saharan Africa. Eastern Africa has a lower rate of HIVAN than would be expected. This data comes from cohort studies done in Kenya and Ethiopia. The risk of HIVAN is associated with APOL1. The Tze Tze fly is not endemic to Eastern Africa, hence no trypanosomes, so no selective pressure for APOL1, so few people are homozygotes for the variant of APOL1 that predisposes to HIVAN.
Patient with acute renal failure and constipation. Normal saline to the rescue.
That’s a low FeNa, but not the lowest I have ever seen.
– Posted using BlogPress from my iPhone
One of my Gitelman patients (whom I kidding, “one of my Gitelman patients”, how about “my only Gitelman patient”) finally got pregnant. We had been managing her with amiloride and a truck load of oral potassium and magnesium supplements. I was shocked to find that amiloride is acceptable in pregnancy with a track record of successful births. Prior to starting amiloride the patient was taking twenty-eight 20 mEq pills of KCl a day. She abandoned her prior nephrologists when she was told to further increase her potassium pills.
 |
| from UpToDate |
We are now using magnesium sulfate infusions 4 grams twice a week to keep her magnesium north of zero. She was able to keep her magnesium around 1.4 with oral supplements and amiloride prior to being pregnant but now, despite 8 grams of weekly IV magnesium her magnesium is sitting around 1.1. This probably represents one of downsides of the up-regulated GFR of pregnancy.
Interestingly, she saw her labs and saw that her sodium was 132. Modest hyponatremia is a normal finding in pregnancy, so she decided to increase her dietary sodium intake. Bad move, increased renal sodium loads increases renal magnesium losses. Her serum mag fell 30% to 0.8.
The title for the talk was dialysis for the internist and I focused on recent advances in the field of hemodialysis including:
Here is a video of me giving the lecture. I’m working on putting together a formal slidecast but the video was a WMV. What a hassle.
Hemodialysis for the Internist. An Update from joel topf on Vimeo.
Tim Cook, at Apple’s forth quarter 2008 earnings call in early 2009, right after Jobs took his first leave of absence to receive a liver transplant:
…There is extraordinary breadth and depth and tenure among the Apple executive team, and they lead 35,000 employees that I would call wicked smart – and that’s in all areas of the company from engineering to marketing to operations and sales and all the rest. And the values of our company are extremely well entrenched. We believe that we are on the face of the earth to make great products and that’s not changing.
We are constantly focusing on innovating. We believe in the simple not the complex. We believe that we need to own and control the primary technologies behind the products that we make, and participate only in markets where we can make a significant contribution.
We believe in saying no to thousands of projects, so that we can really focus on the few that are truly important and meaningful to us. We believe in deep collaboration and cross-pollination of our groups, which allow us to innovate in a way that others cannot.
And frankly, we don’t settle for anything less than excellence in every group in the company, and we have the self-honesty to admit when we’re wrong and the courage to change. And I think regardless of who is in what job those values are so embedded in this company that Apple will do extremely well…
Just like everyone, I want Steve Jobs to get better. I want to live in a world where the man who launched the PC revolution is still leading it. All the news today, however, is about how doomed Apple is without Jobs. It’s a little over the top. Look at Tim “acting CEO” Cook’s words. That is an off the cusp speech and it is pitch perfect. Those words could’ve come right from Steve’s brain. Apple is going to be fine.
Hat tip to Asymco