Friday, February 28, 2014

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

Wednesday, February 26, 2014

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.

Monday, February 24, 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.

Tuesday, February 18, 2014

#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.

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.

Thursday, February 13, 2014

My apple predictions for 2014

In the past I have posted my Apple predictions on PBFluids, but I am going to keep this blog kidney focussed, so I posted my 2014 Apple Predictions on Medium, a fantastic blogging platform if anyone is looking to start writing online.

Tuesday, February 11, 2014

#DreamRCT: Prevent DeaDD

Swapnil Hiremath, a nephrologist from the great white north has taken up the call and has submitted the sixth #DreamRCT. I met Swapnil on Twitter where he is quite clever and insightful about nephrology research. Swapnil works in Ottawa, which is apparently Canada's capital.

He writes, "In Ottawa, we are not fazed with the polar vortex - in fact our annual winter festival, the Winterlude is going on now." He is a true citizen of the world who made it to Ottawa from Mumbai, where he trained at King Edward Memorial Hospital. After Mumbai he proceeded to Boston to pick up an MPH from Harvard. He is currently an Assistant Professor in the faculty of Medicine at the University of Ottawa. His turn-ons are epidemiological studies in acute kidney injury, resistant hypertension and vascular access. See his citations at Google Scholar.

His DreamRCT takes a swap at the high rate of CV death in dialysis patients by randomizing ICDs to them. Clever and important idea. I love that he didn't dream small and took a shot at one of the most important issues in dialysis. His post is hosted at Medium. Read it here.

Sunday, February 9, 2014

#DreamRCT update: PHLane comes through

That was fast, moments after posting my plea for more entries, Pascale Lane posted her entry:

O My

Andin the grand tradition of big science, she already has the follow-up study planned before unrolling patient 1 in the first study. I can't wait for NOMAD. Read it. Great work.

Her T-Shirt is in the mail.
You could be next.
Get'em done. Post'em up.

#DreamRCT deadline approaches

We want to open the voting for the DreamRCT a week from tomorrow, but we are running into an obvious problem, we only have 4 entries which seems a little light:

  1. The Uric Acid causes CKD RCT that I did
  2. The Phosphate trial that Jordan did
  3. The IMAGINE trial by Paul Phelan at the Renal Fellow Network
  4. PHANTOM-1 trial of anticoagulation in ESRD by Ed El Sayed

Every nephrologist I know complains about the woeful state of evidence in nephrology, but in my mind if you can't come up with a a DreamRCT, you have no legs to stand on.

Please write it up because if we don't get it done Jordan has all kinds of Plan B's that I don't want to consider.

To sweeten the deal, we have DreamRCT t-shirts. The next six people to post their dream RCT will get a T-shirt complements of yours truly. Time to raid my wallet. Write your damn DreamRCT already.

What? You say you don't have a blog to publish it? 
No problem, I'll host it here at PBFluids. 

What? You say you would never post it to PBFluids, because Joel was once a dick on Twitter?
No problem, tweet at Jordan Weinstein (@UKidney) I'm sure you two can work something out, or go post it to Medium.

What? You say you have enough T-shirts?
No problem, I'll send you a mug instead.

Thursday, February 6, 2014

#DreamRCT: Anticoagulation in Hemodialysis

Back in December, I had Ed El Sayed (@iApothecary) do the first guest post on PBFluids. He wrote about Nephron D for the top nephrology stories of the year project. It was one of my most popular stories of the fourth quarter of 2013. Ed is back with his contribution to the DreamRCT project:

When should dialysis patients with non-valvular Atrial Fibrillation be anti- coagulated?


End Stage Renal Disease (ESRD) patients on dialysis have an increased risk for bleeding due to a number of factors, most notably failure of uremic platelets dysfunction (decreased degranulation and aggregation). This increases the risk of therapeutic anticoagulation in dialysis patients, they just have a significantly increased risk of bleeding.

Quantifying this risk is important because in numerous clinical situations the choice to anti coagulate or not to anti coagulate must ejudicated. Often times, clinicians are faced with an issue where the evidence base simply does not exist, or is unfortunately, ambiguous. When trying to determine if anticoagulation for atrial fibrillation is appropriate in ESRD patients, nephrologists, cardiologists, and pharmacologists cannot mine the medical literature for an answer. The evidence is insufficient.

That being said, experts recommend anti-coagulation pharmacotherapy in ESRD patients who have one or more of the following conditions: 
  • Pulmonary Embolism
  • Deep Vein Thromboembolism
  • Anti-Phospholipid Syndrome
  • Mechanical prosthetic cardiac valve
This expert recommendation is based on the hope that the anti-coagulation benefits in those conditions outweighs the risk of bleeding.

So where do we stand?

The Dialysis Outcomes And Practice Pattern Study (DOPPS) trial and the United Stats Renal Data Service (USRDS) both demonstrated an increasing rate of atrial fibrillation (AF) among dialysis patients. AF was also shown to be more prevalent in pre-dialysis CKD patients in the Chronic Renal Insufficiency Cohort (CIRC) trial. Even more worrisome is data showing that AF in ESRD patients increases all cause mortality. On the other hand, the data is inconsistent on the association between AF and stroke in ESRD patients (no association: here, and here, positive association: previous KI article).

Another dilemma clinicians often face in clinical practice is whether to use the CHAD2S2 score to assess the need for using warfarin to prevent stroke in AF patients on dialysis. While the CHAD2S2 score is a derivative of CHADS2 score, its validity was based on data from non-renal patients and experts advocate against using it on renal patents.

Several studies have been performed to determine the benefit of warfarin in AF patients on dialysis. The results however, were inconsistent. A few studies were pro-warfarin, while others were anti-warfarin.

Despite numerous studies, prospective data is both scant and contradictory. The data in patients without renal insufficiency, while compelling cannot be used to judge the safety and efficacy of anticoagulation in dialysis. This means we do not have the data to make the decisions we need.

My Dream RCT: The PHANTOM-1 Study

Placebo in Hemodialysis vs ANTicoagulation. My aim is to design a multi-center, randomized, double blinded, placebo controlled trial to study the effect of Warfarin pharmacotherapy in AF patients who require hemodialysis. PHANTOM-1 study would have the following criteria:

  • Inclusion Criteria
    • Age range 50 - 84 years
    • Sex males and females
    • CHADS2 Score greater than or equal to 2
    • History of Non-Valvular AF for 2 or more years
    • On Warfarin with INR 2-3
    • Ethnicity White, Asian, African American
    • History of ESRD requiring hemodialysis 3 or more times weekly
  • Exclusion Criteria
    • Age range younger than 50 years and older than 84 years
    • CHADS2 Score less than 2
    • AF secondary to valvular disease
    • History of Non-Valvular AF for less than 2 years
    • On Warfarin with INR below 2 or above 3
    • Renal disease without the need for hemodialysis
    • ESRD patients undergoing Peritoneal Dialysis
    • History of Neuro-endocrine disease

The study design would have 2 arms, with one group continuing to receive oral warfarin 5-10 mg once daily to maintain INR between 2-3, while the other group receive a placebo. The outcomes of the study would be as follows:
  • Primary Endpoint - Onset of Transient Ischemic Attack (TIA) or stroke (Ischemic or Hemorrhagic)
  • Secondary Endpoint - Incident of major bleeding (outside the CNS) and access survival.
All patients in the trial would receive multi-disciplinary medical counseling and monitoring throughout the study time frame. The result of the study would be welcomed and published, regardless of the outcome.

Prospectively studying this in a randomized, placebo controlled trial would definitively answer an increasingly common question that nephrologists, cardiologists and primary care doctors face.


I received this feedback:
As a long time hematologist with an interest in anticoagulation I was very interested by your post as this is something my nephrology colleagues and I discuss all the time. I would also advocate enrolling folks not currently on anticoagulation because even in the non-dialysis population a lot of patients with afib who should be on warfarin are not. The other issues is would renal dose adjusted new direct oral anticoagulants be safer (50% Risk reduction of ICH in trials) esp when the antidote become available.
if this program gets rolling let me know how I can help.
--tom Thomas DeLoughery, MD FACP FAWMInterim Associate Division HeadProfessor of Medicine, Pathology and PediatricsOregon Health & Sciences University
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