Monday, April 30, 2012

eAJKD: integrated care

I interviewed Allen Nissenson for eAJKD. He wrote a great review of his knowledge and experience with accountable care organizations and how they will affect nephrology. The best part of his article was when he discussed his experience working on a pilot project for CMS demonstrating benefits to dialysis patients using an integrated care model. This project showed a survival benefit not by changing the dose of dialysis, or giving additional drugs. The improved outcomes came simply from better communication and organized, systematic care. Eye-opening stuff.

Sunday, April 29, 2012

Uric acid and hypertension, a unique study

I have written and presented quite a bit about uric acid, fructose and the link to hypertension and chronic kidney disease. Last month's Kidney International published an interesting take on this subject.

The question that the investigators were examining was, "Is uric acid a cause of hypertension?" The data supporting this is largely epidemiologic, with a smattering of interventional trials. The largest criticism of the epidemiological trials has been the issue of causality and directionality, i.e. does the hypertension cause the high uric acid or does high uric acid cause the hypertension?

this is how I show the directionality debate in my presentation

Previous interventions involved using allopurinol to decrease uric acid. However there are questions of whether allopurinol may have some magical anti-hypertensive effect outside of its ability to lower uric acid. The investigators discovered a cohort of Amish with a variant of GLUT9, a urate transporter. This variant, an ILE for VAL at amino acid 259, lowers the uric acid level by about 0.5 mg/dL in women and 0.25 in men. The lowered uric acid is likely due to enhanced renal clearance.
The authors used Mendelian Randomization to see what the effect of a lower uric acid has on developing hypertension.

Mendelian randomization (MR) is a concept I had not come across before. Here is a video of Wayne State University researcher, Dr Anthony Ference, who used MR to study LDL. He does a nice job of describing the concept.

The authors of the uric acid acid trial describe mendelian randomization thusly:
The mendelian randomization principle relies on the tenet that alleles, and hence genotypes, are randomly assigned during gamete formation. The main advantage of this method is that gamete formation occurs before birth and is therefore unaffected by traditional confounders that occur after conception, such as diet, socioeconomic status, access to healthcare, and all other environmental factors. Because relationships between genotypes and outcomes have only limited susceptibility to confounding and are not subject to reverse causality, genetic variation may be used to establish directionality and infer causality between a certain gene product and a specific outcome. Therefore, Mendelian randomization is akin to a randomized trial design, inheritance of the GLUT9 ILE allele would be analogous to randomly being assigned probenecid, a uricosuric agent, from birth, whereas inheritance of the wild-type genotype would be analogous to receiving placebo.
The cohort was a group of 868 participants of the HAPI (Hereditary and Phenotype Intervention) study. Ninety-eight of these people had GLUT9 variants. Patients' blood pressures recorded in clinic on a liberal (standard) diet and then checked with 24-hour ambulatory monitoring following a week on a high-sodium diet (280 meq/day) and again after a week on a low-sodium diet (40 meq/day). The diets had fixed carbohydrates and potassium.
The blood pressure spread is impressive and statistically significant in both the high- and low-sodium diets. The authors summary was for every 1 mg/dl decrease in uric acid the systolic blood pressure fell by 3-5 mmHg.

I thought this study was an original approach to the question of fructose and uric acid. They found an experimental method that allowed them to look at different levels of uric acid without confounding the results with the pleiotropic effects of allopurinol.

Thursday, April 26, 2012

The nephrologist's guide to Twitter

Twitter is the second largest social network after Facebook. But, though they are often grouped together this is not a Coke and Pepsi type of pairing. Twitter and Facebook are different animals.

The difference stems from a fundamental difference in the construction of the networks. In Facebook, both parties must agree on the relationship. Once you have "friended" each other, you are on roughly equal footing. This mutual agreement to exchange information gives people a sense of privacy that Facebook is repeatedly jeopardizing as they lurch from dorm room experiment to world changing company.

Twitter, on-the-other-hand promises neither privacy nor mutuality. People sign up to "follow" your updates and you can choose to follow them, or not. This changes everything. It allows celebrities to use twitter to broadcast to a wide audience. It also thrives at allowing people to communicate with people they have never met.
It has been said: Facebook allows you to connect with people you already know, Twitter allows you to meet people you want to know.
A more cynical version of this is:
Facebook is where you lie to people you know. Twitter is where you're honest with strangers. @Berci, author of a great Prezi on Twitter in Medicine
The best part of Twitter is that it highly flexible and each user has complete power to customize her experience.

The three fundamental things anyone needs to know to get started on Twitter are:
  1. Who to follow
  2. What to do
  3. What to say
Who to follow
I would categorize who to follow in various slots. I will highlight people I think are important to follow, not because I believe in what they say but because they illustrate an angle to Twitter that helps the neophyte understand the medium. is a service which tracks the most popular tweets. It is a good tool to see the best of what a person is capable of Tweeting.

@BurbDoc (FavStar) provides a few lessons. The first he is the quintassential example of unprofessional behavior on Twitter. Burb is a primary care doc who has been driven over the edge by the inanity of suburban America and a primary care system disrespected by clueless patients, arrogant specialists, absurd insurance companies, immoral drug companies, and meddling bureaucrats.

Typical NSFW Tweet from @BurbDoc
BurbDoc does not use his real name on his Twitter account. There is no way he could use his real name and Tweet with the style he uses. There are long debates on the merits of anonymous tweeting. I'm a firm believer of tweeting with your name, it will remind you that you aren't scrawling graffiti behind the high school but posting a permanent billboard on the road called Google. Sign your name and you will be more careful with what say. And you never are as anonymous as you think you are.

@DrVes (FavStar) is a professional medical blogger. He is an Assistant Professor at the University of Chicago and blogs at He is a prolific tweeter covering a broad swath of medical news each day. DrVes is broadly followed and well respected among Twitter doctors. Typical tweet:

@KidneyNews (favstar)is the primary twitter account of KidneyNews, the magazine of the American Society of Nephrology. It may seem similar to @DrVes as it is a continuous stream of kidney stories. The primary difference is that DrVes custom crafts each tweet. KidneyNotes is a bot that automatically posts links to every post from a host of kidney focused blogs. If you want to keep a finger on the pulse of the renal blogosphere this is an easy way to keep up. Pacale Lane, a Pediatric Nephrologist, runs the KidneyNews twitter feed. She also has an individual twitter account at @PHLane (favstar)

Similar to KidneyNews is @TheKidneyGroup (favstar). This nephrology group has established an exemplary social media presence in nephrology. They have active Facebook and Twitter feeds. The tweets usually contain stories about transplant or quirky stories of scientific advancement. The feed doesn't seem to be managed by a doctor, but rather an enthusiastic employee (spouse?) of the group.

If you want to skip the ASN middleman you could follow the top renal blogs directly:
Also you can consider following the blog authors personal accounts:
There are other nephrologists who use Twitter as their only online presence. Two examples I like are:

@BrianLee is a nephrologist in Hawaii. He is not a high volume tweeter with a tweet or two every few weeks. He uses Twitter to comment on blogs, spread news stories or celebrate his victories.

He always comes across as professional and well informed. A nephrologist could do worse than model his use of Twitter after Brian Lee.

In this same vein is @KnittingNephron (favstar). She is much more prolific than Brian but since most of the tweets are @ replays they will not show up in your stream, until she drops a bit of renal wit.

Two final twitter accounts that you should consider following. @Skepticscalpel (favstar) is a surgeon who tweets about evidence based medicine, trauma, and medical education. Sharp wit.

Shad Ireland is an athlete on dialysis who is training to swim/bike/run the IronMan Triathlon. He does home hemo and is an inspiring example of what you can do despite dialysis. @IronShad

What to do

Example of a twitter conversation. Read from the
bottom up, click to get a larger, readable copy.
There are three ways to interact on twitter, a reply, a retweet and a favorite. That order is in descending order of engagement. Meaning, if you want a meaningful, interactive Twitter experience, be quick to reply and worry less about favorites.

The simplest to understand is the reply. You see a tweet you appreciate, and you acknowledge it by engadging with it. You direct the message to the author by starting the tweet with their user name: @Kidney_boy to reply to me.

If the reply begins with the twitter handle only people following both parties will see the tweet. This clears out a lot of private chats from your Twitter stream. People that follow just BurbDoc or just me will not see the tweet. People sometimes add a period before the @ so everyone will see the tweet.  

A retweet is a way of saying "I like this." It amplifies the writer's message. Favstar tracks retweets as a way of measuring the popularity or impact of a tweet.

Tweets I have starred
Favorites are a way to honor tweets that you like and it also marks them and collects them so you can review them later. There is no reaction on the public timeline when you favorite a tweet, however people can see what you have favorited by going to your profile page. Stars are not private. Sarah Palin got a bit of heat by making this mistake.

In Twitter for the Mac, each of the interaction functions are just a click away.

Medical Twitter Chats
In addition to the above methods of interaction I suggest exploring some of the regular medical chats that happen a few times everyday.

I like three chats, though I don't participate that often, I always enjoy them when I do. To participate in the chats, search for the HashTag for the chat (#TwitJC, or #HCSM, etc). When you want to add your 144 characters, make sure to append the hashtag so other people can find your comment.

On every second or third Sunday there is the Twitter Journal Club. It is an innovative combination of a website and twitter chat. The organizers post an article and an introduction in the week leading up to the chat. Then during the appointed time the organizers ask pointed questions to tease out the complete story of the article. The discussion uses the hastag #TwitJC. Every other Sunday at 3 pm EST. (7 pm GMT)

Sunday Night from 7-8 pm EST is health care and social media chat. This is the oldest medical twitter chat. It started in 2009. If you want to use twitter to talk about twitter, this is the place for you. The hashtag is #HCSM.

Thursday at 9 pm EST is the MedEd chat. This is one of my favorites. The discussion is lively and generally the people are interesting. Hastag #MedEd.

What to Say
Everyone needs to find his own voice on Twitter. That said, I have a bit of advice. Firstly, remember that everything you say will be permanent and associated with you. Staying quiet initially and watching is a good way to get started. Find people you like and respect and see how they interact on Twitter. Like anything in medicine, imitating respected mentors is a good way to learn.

Probably the best pithiest advice and on how physicians should behave on Twitter comes from the Mayo Clinic and their twelve word social media policy:
Don’t Lie, Don’t Pry
Don’t Cheat, Can’t Delete
Don’t Steal, Don’t Reveal

Monday, April 9, 2012

You hear about the kid who sold his kidney for an iPad?

This tragic story has been flying around the internet for the past few days. The story was broken in the western press by Reuters who described a 17-year old named Wang from Hunan who was paid $3,500 for his kidney which was subsequently sold for $35,000 to a patient in need of a transplant. The story originally surfaced last April (strangely his name at that time was reported as Zheng, but so many of the details line up I'm certain this is the same kid) but now that five people are being prosecuted and poor Wang is suffering from renal insufficiency the story is "hot" again. Apparently Wang will likely need a kidney transplant of his own soon.

The part of the story that irritates me is the implication that donating the kidney is the cause of Wang's failing kidney. This is implied and to the lay person it makes total sense. God gave you two kidneys. You better not donate one or you could end up needing a transplant yourself.

This is the wrong conclusion. Donating a kidney does not increase your risk of dialysis, transplant or poor quality of life. This is best illustrated in Ibrahim et al's retrospective study of 3,698 kidney donors from 1963 to 2007.

The study population was the entire cohort of living donors from the University of Minnesota. This population, prior to donating is free of diabetes, hypertension and had a GFR >80 mL/min. Additionally they had no albuminuria. Of course, many of them had a relative with ESRD.

Eleven of the 3,700  (0.3%) donors ultimately needed dialysis or transplantation. The average time from donation to ESRD was 22.5±10.4 years. Seven of the unfortunate, donated to a sibling and only three lost their kidneys due to the same etiology as their recipient.
...estimated incidence of ESRD in donors would appear to be 180 per million persons per year, as compared with the overall adjusted incidence rate of 268 per million persons per year in the white population of the United States.
Idea: to lower the epidemic of ESRD, get everyone to donate a kidney and we can reduce the incidence of ESRD by a third.

The remainder of the article goes through the deep analysis of the 255 donors who were invited for further testing.

  • Creatinine had gone from 0.9 at the time of donation to 1.1 an average of 12 years later
  • GFR went from 84 to 63 mL/min
  • 11.5% developed microalbuminuria
  • 1.2% developed macroalbuminuria

Thirty-eight donors have returned for two iothalamate GFRs at least 3 years apart. The investigators found the average loss of GFR was 0.6 mL/min per year.

One of the reasons that donating a kidney is safe is that the remaining kidney undergoes hypertrophy to accommodate the increased work-load. The investigators were able to provide some insight into the variables which govern this. Increased compensation correlated with:

  • younger age at donation
  • higher renal function at donation
  • longer time since donation

This final graph should be the take away for discussing kidney donation:
Kidney donors report better physical and mental health than the US average.
When I counsel patients on the safety of kidney donation or medical nephrectomy I need to fight the pre-conceived notion that loss of renal function occurs nephron-by-nephron, so that losing half the nephrons through a nephrectomy halves the time to dialysis. People seem to visualize kidney function like a bathtub draining water. High blood pressure and proteinuria open the drain wider so the water drains out faster. Using that visualization, a nephrectomy is like losing half the water and putting you much closer to dialysis.

The image I try to paint is that losing renal function is like melting an ice cube, people start with two ice cubes. When the ice is gone the patient needs a transplant or dialysis. Poorly controlled blood sugars, high blood pressure and proteinuria turn up the ambient temperature so the ice melts faster, but it melts both the left and right cube at the same time.  A nephrectomy removes one of the ice cubes but it does not necessarily reduce the time until all the ice is gone.

The last point that needs to be made about this story is that shady, back-street organ selling scams are designed to line the pockets of the broker and surgeon. They do not have the best interest of the kidney donor in mind. The tragic outcome of young Wang is typical for these third-world, kidney-for-money scams. JAMA published a great article showing the typical experience in India a decade ago. It's still worth reading.

Thanks to Dr. El-Ghoroury for help with this post. Follow him on Twitter @melgho
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