My post for World Kidney Day

Things a re a bit frantic with the start of NephMadness just over 24 hours away.

Sitting on the flight deck of #NephMadness One. Note the glom pic the wife got me for Valentines day! pic.twitter.com/iMLgTlidQR
— Joel Topf (@kidney_boy) March 12, 2014

I posted on World Kidney Day at Medium but I failed to link to on PBFuids. Sorry.

My very optimistic post for WKD


I’m going to be doing more and more of my posts on Medium, it is so much better than WordPress or Blogger for composing and displaying my words.

Follow-up from the Herbal Supplements Lecture

I received a delightful e-mail from Arthur Grollman, world expert on Aroistocholic Acid.

Dear Dr Topf, 

I congratulate you on assembling and sharing this very nice presentation and, wisely, connecting it to the problems associated with politicians, supplements and DSHEA.  We have written some articles about this connection as well. 

I give a similar lecture to medical students and another focussed on BEN [ed: Balkan Endemic nephropathy] and aristolochic acid nephropathy for Medical and Nephrology Grand Rounds as most of the research being done on that subject since 2005 has been done in our lab. 

A few comments on the historical sequence:

  • JP Cosyns is the Belgian pathologist who first recognized the similarity to BEN but did not follow up the lead
  • Tjassa Hranjec, a medical student at Stony Brook, doing a summer fellowship conducted the personal  interview with the farmer you attributed to me. She
  • was doing a pilot epi study, under my direction, to determine how we should investigate BEN
  • The first experimental evidence for the role of AA in AAN and UTUC appears  in our 2007 PNAS paper
  • The Serbs and the Bosnians still believed that their BEN was a different disease, so we expanded the number of cases and included those countries in the cover story paper in KI in 2012.  DeBroe wrote a commentary to accompany our paper which convinced any remaining skeptics of the validity of our guiding hypothesis: AAN = CHN = BEN
  • Wondering how Aristolochia herbs could have been used throughout the world for 2000 years without one mention of toxicity or urothelial cancer, we conducted the study in Taiwan, where one in three people have ingested the Aristolochia herb according to the prescription database.  The results are in our 2012 PNAS paper.

We continue to work on this fascinating nephrotoxin/carcinogen for which, as you see has a “signature mutation” and is likely to affect tens of millions of people in China.  And the road to its recognition started exactly as you said in your talk, with the two
Belgian women in Vanderwegen’s clinic. He told me that his own clue came when he walked from his office to the clinic and found a number of women talking to each other which was unusual. He asked them how they knew each other which led immediately to the identification of the spa. 

With best regards 

Arthur P. Grollman M.D.
Distinguished Professor of Pharmacological Sciences
Evelyn Glick Professor of Experimental Medicine
Director: Laboratory of Chemical Biology
Health Sciences Center BST-8-160
Stony Brook University

The e-mail included some great images. Two covers from nephrology journals:

Gorgeous picture of DNA Adducts
Grollman won the 2011 Environmental Mutagen Society Award. As part of that award he wrote an invited review on aristocholic acid nephropathy. I’m looking forward to reading it. It has some great drawings. Take a look at the figure below the abstract. Wow.

#DreamRCT: The final push

The DreamRCT project launched just over a month ago on January 28th. It has exciting seeing people across the nephrology blogosphere participate in this project. But all good things need to wrap-up. NephMadness is approaching so it is time for everyone to rank their favorite post.

Go to UKidney to view and rank your favorite DreamRCTs

The voting is currently neck and neck, help push your favorite over the top! And if you have a great idea for a DreamRCT, get in quick, the doors are still open. Having trouble coming up with an idea, how about pone of these:

  • Systolic blood pressure targets in proteinuric disease less than 140 vs  less than 130. Fill in the hole left from ACCORD BP.
  • Fixed ESA dose vs pharmacodynamic dosing (current standard of care). This editorial gets at some of the issues I’d like to explore, but doesn’t fully flesh it out.
  • PTH liberal strategy vs conservative PTH strategy. Randomize patients to get PTH lowering therapy based on target PTHs, current standard of care versus only intervene for symptoms such as bone pain and itching. Answer once and for all, is PTH important?

I have one more idea for a totally crazy DreamRCT that I will try to submit in the next few days.

Lecture on Herbal Medicine and Kidney Disease

In August of 2013, I went to Chicago for the ASN Board Review Class. The week long class was filled with great lectures and compelling teachers, but it was a review and I had solid knowledge of most sessions, but one session was different. Warren Kupin (Hey, Warren, we are still waiting for your first tweet!) of the University of Miami gave an inspired lecture on interstitial nephritis and the dangers of herbal medications. It was one of the most interesting lectures I have ever seen and I decided that I would remix his lecture for my February grand rounds.

I gave this grand rounds at St Johns and Providence Hospital last week (two grand rounds, same subject, same week, that’s lecturing like a boss).

Here is a link to see the presentation with me narrating.
Same presentation but higher quality.

The original Keynote file is available here for remixing and editing.

A PDF of the presentation is available here.

Notes on the presentation

Much of the information on sulfanilamide comes from this article by the FDA.

The picture comes from an ad on Etsy. I didn’t get permission to use the photo, but I did buy the bottle, so that should be cool.

Harold Watkins committed suicide after the sulfonilamide disaster, though the owner of the Messengill Company never showed any regrets: Dr. Samual Evans Massengill, the firm’s owner, said: “My chemists and I deeply regret the fatal results, but there was no error in the manufacture of the product. We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part.”

Diethylene glycol, though it contains two molecules of ethylene glycol there is no evidence that it behaves like ethylene glycol in a poisonong and no evidence that fomepizole would be protective. Contemporary experience with diethylene glycol comes from the Haiti Contamination disaster and a PDF from JAMA.

There are various reports for how much was shipped and how much was confiscated, I took one set of data and ran with it. If I’m wrong, shoot me.

The Kelsey information is almost entirely from Wikipedia.

@kidney_boy One (minor) thing – McGill University is in Montreal, not Toronto. Can get folks upset here in Canada. 🙂 (McGill grad here)
— Michelle Gibson (@MCG_MedEd) March 4, 2014

Getting reliable data on the size of the herbal supplement business was nearly impossible, I found sources that used anywhere from 5 billion to 100 billion. Most sources were around 26 billion so that is what I used. I imagine it depends a lot on what you includein dietary supplements and herbal medication. Of note, GNC alone does 2.6 billion dollars in revenue.

I like this slide, but it doesn’t really fit into the lecture. I bet it gets cut in a future presentation.

The tag line that people take the drugs for years, what they may take changes but they will take something for years, comes almost verbatem from Kupin’s lecture.

I really like the chart styles I used in this lecture. One of the problems with pie graphs is trying to associate a color to a trend. what part of the pie is attached to what is happening. By making one color with maximum contrast and the other with no contrast (transparent), it becomes much clearer. If I were to change anything I would get rid of the title of the slide and increase the typeface over the pies. Kupin’s slide with the same data for comparison.

The silicate stone story is a little weak and could be cut.

Love this slide. Kupin’s idea to leverage physician familiarity with Grapefruit interactions with how St. John Wort interacts. He is really clever.

The Metabolife story is so good it should be made into a movie. And the only reason there is an anvil animation is so you can drop the bars over some guy. Love this slide.

The Seville Orange and synephrine works great. The Blue Cohosh data is a little light and the fact that there aren’t a million weight loss agents using it makes me suspect that it is not a very powerful alpha agonist. May need to research this herb more thoroughly.

I need to include the incredible aspect that Patrick Arnold was the guy who brought DMAA back from the dead. Patrick Arnold was the chemist behind BALCO and inventor of The Clear.

Wife helped me with this slide, the first version had patient temperatures and ambient temperatures on a single thermometer.

The Cheerios story is cute, and illustrative but it could be sacrificed.

One of the funniest parts of Kupin’s talk is when he goes off on the crazy ridiculous packaging of herbal medications (American products waving the Dutch flag, etc.). I couldn’t pull it off and added this single slide. I may talk a bit more about the packaging requirements of DSHEA.

This slide worked as well as I hoped it would. Big risk talking about erections for a slide with 43 builds. It worked.

Weight loss supplements, go home, you’re drunk.
Phenolphthalein. Really?

The Glycyrrhiza glabra joke? It’s Kupin’s. The guy is really funny.

The 11beta-hydroxysteroid dehydrogenase story comes from my metabolic alkalosis, potassium and monogenic hypertension lecture.

It’s principal cell not principle cell. Thanks Matt.

Love this twist to the Aruvedic medicine study. I find it so funny, it is the kind of thing that usually doesn’t make it into the methods. #OverlyHonestMethods

Kupin spent a lot of time in his lecture talking about this. I blew through it pretty quickly. I may make time for this in a future version.

Love the way I told the Aristolochic Acid story. And this story board where I select the different countries turned out just like I hoped it would.

The most important slides in the deck?

This slide didn’t work as well as I would like.

The next version should add some of the data I started to put together on vitamins, especially the SELECT trial and the USPTF statement saying that vitamins have no role in the prevention of cancer of cardiac disease.

The frequent hemodialysis network long term follow-up

The FHN trial of 6-times versus 3-times a week in-center dialysis was famously a modestly positive trial. It was not powered to show a mortality benefit and as expected, it did not show a mortality benefit. This year at Kidney Week, Chertow and the FHN Team presented a poster with subsequent follow-up of the randomized patients. While almost all of the patient migrated back to conventional 3-days a week dialysis after the trial, they found that patients randomized to daily in-center hemodialysis have had a better survival than patients randomized to 3-times a week dialysis. The Hazard ratio was a healthy 0.54!

How did this not get an oral presentation?

You can find it on page 442 of the 2013 abstract supplement, which you can download here.

You may or may not see this in #NephMadness

Biochem 411 with Dr. Beyer

Just about anyone who was pre-med at the University of Michigan in the 80’s and 90’s probably took Biochemistry 411. It was a unique class, that used the Keller Plan, an early experiment in flipped classrooms. Professor Robert Beyer created a course book which laid out explicitly what the expectations were for each of 15 modules. Students would study on their own until they understood the expectations and then take a test demonstrating mastery of the material. If they had questions they could work with student proctors to get the answers.

It was an awesome class, it was the only A+ I ever received. The class was essential med school prep because it taught me how much crap I could stuff into short term memory for a test. You can see an overview of the class Dr. Beyers wrote for an education journal here.

Dr. Beyer offered optional lecture sessions if you wanted to learn additional ancillary information and I went to a few of them. He did an awesome lecture on the benign medical nature of marajuana. He did a lecture on the importance of free radical scavengers (he was a huge Linus Pauling fan, who he called the great brain). Here is some lay press  on some of his research on free radicals. And he had a few pet molecules that he loved, one was Co-enzyme Q10. I knew more about Co-Enzyme Q than I ever thought I would need and I was pleasantly surprised to see it pop back up as a relevant medical drug twenty years later.

Another pet molecule (or I guess, element in this case) was selenium, he gave a convincing lecture that increased selenium was the key to preventing cancer. This has not worked out so well. The Select trial randomized 35,000 men to placebo, vitamin E, selenium or both vitamin E and selenium. The lowest prostate cancer rate was with placebo. Sorry Dr. Beyer.

The Journal of National Cancer Institute this week released a nested case control analysis of the same data and found that selenium and vitamin E increased the risk of prostate cancer by 90% in some patients.

Sure, take a vitamin a day, how could it hurt (besides doubling your risk of prostate cancer) http://t.co/gQCNr1YmyF H/t @drarcox
— Joel Topf (@kidney_boy) February 23, 2014

#DreamRCT late entry: FHN Do Over

Jason Prosek has submitted another DreamRCT. Jason is an assistant professor of nephrology at the Wexner Medical Center at the Ohio State University.  He is a general nephrologist with particular clinical interests in onco-nephrology and heart failure / ultrafiltration.  He is also heavily involved in fellow education.

Jason’s RCT is trying to actually put Tessin’s hemodialysis strategy to the test. It is an interesting trial and an ambitious idea. Check it out on Medium.

Jason can be found on Twitter.

#DreamRCT Phase 2

For the past few weeks a few contributors have posted their personal ideas about the biggest

questions in nephrology. These ideas were presented in the form of proposed randomized controlled trials. Here is the cohort of #DreamRCTs so far:

I am grateful to each one of them that took up the call and contributed to this endeavor. For their time each one has received a DreamRCT mug or t-shirt.

I’m on the Dream Team #dreamRCT pic.twitter.com/Bh0wDI9KNP
— Pascale Lane (@PHLane) February 18, 2014

Dream it. Do it. My #DreamRCT in Nephrology, & hot tea from my new favorite mug! Thanks, Joel! @kidney_boy pic.twitter.com/c0n8VQp9LR
— ⓔⓓ ⓔⓛ ⓢⓐⓨⓔⓓ (@iApothecary) February 15, 2014

UKidney has collected all of the ideas and listed them together for the community to rank these ideas. But additionally, and importantly, they have provided a mechanism for everyone to contribute their own ideas for a DreamRCT. Go to the site, check it out and contribute. Nephrology is full of dark neglected corners that could use the bright light of a well conceived, randomized controlled trial.