Friday, January 31, 2014

hypokalemia and metabolic alkalosis

A few years ago I was talking one of my mentors at Kidney Week, John Asplin. He mentioned
that he taught an integrated lecture on metabolic alkalosis and hypokalemia. I thought this was an inspired idea.

Teaching separate classes on both subjects results in a lot of overlap because the renal mechanisms for both disease are the same, this means that many of the diseases that cause one, also cause the other.

Additionally hypokalemia can cause metabolic alkalosis and metabolic alkalosis can cause hypokalemia, so it makes sense to teach both of these conditions in an integrated lecture.

Lastly, teaching each electrolyte individually in isolation from each other is a missed opportunity. One can only appreciate the beauty of electrolyte physiology when one understands how each electrolyte fits together and how abnormalities in one is associated and affects all of the other electrolytes.

Unfortunately, I botched the lecture. I gave this lecture for the first time for the Oakland University Beaumont Medical School this past August. I knew it didn't go too well, but this week I received the class feedback. Overall my statistical evaluations were excellent but when I read the comments the students were jackals. They savaged this lecture.

Timing was on my side, I was scheduled to give this lecture the day after I received feedback. I'm not done tweaking it but what I did for my Tuesday lecture was add more connective tissue between the concepts, and fill in with some additional summary slides.

Right now, I'm using it as a lecture to follow-up my potassium lecture, but at OU the students didn't have any baseline potassium knowledge. In order for this lecture to work the students must already understand the basics of potassium, especially the central role that renal potassium handling has in potassium homeostasis. Hopefully I will be able to negotiate another hour into the GU schedule for this lecture.

My next plans for this lecture is to cut out a lot of the opening slides. The purpose of those slides is to quickly move from introducing potassium and hypokalemia to getting to the truth that hypokalemia is almost solely a disease of increased renal losses.

I want to add a slide about disease opposites:
  • Pseodohypoaldosteronism type 1 and Liddle syndrome
  • Godon's syndrome and gittleman's syndrome
  • Adrenal insufficiency and AME
I want to add some slides on how hypokalemia causes (specifically, maintanes) metabolic alkalosis and then how metabolic alkalosis causes hypokalemia.

Here is the lecture (Keynote version | PDF)

Tuesday, January 28, 2014

#DreamRCT: Prove the uric acid-CKD connection and win Richard Johnson a Nobel

Okay nephrologists, we have suffered the slings and arrows of outrageous trial after trial going
against us. It is time to put down those depressing journals full of non-significant P values and stretch our imagination. It is time to design our own dream randomized controlled trial. The assignment is to target the most important question you see in nephrology today and design a trial to answer it. One question not enough for you? Design a trial to answer two questions ACCORD style, two questions not enough, go all AASK and design a 2x3 factorial design. Money no object, forget about pesky IRBs, let your mind free and create the trial which will meaningfully push back the walls of knowledge.

After you post your entry at your site of choice, UKidney will host a summary with a link for each entry and gather votes for the best. You can take a look at Jordan Weinstein's Dream RCT here.

And may the IRB be ever in your favor.

My Dream RCT: Background

Humans have higher uric acid levels than almost other animals. This is primarily due to the lack of uricase, but also due to our efficient renal reabsorption of filtered uric acid by URAT1 and GLUT9. Traditionally, it has been believed that hyperuricemia causes renal disease by precipitating intraluminal crystals, analogous to gout crystals in the joints. More recent data however, implicates lower levels of uric acid in hypertension and chronic kidney disease through suppression of nitric oxide formation, stimulation of inflammation through NF-kappa beta and other mechanisms. Supporting these theories are animal studies that show febuxostat and allopurinol reduce renal damage in multiple models of kidney disease (here and here).

Epidemiologic studies linking uric acid to chronic kidney disease show a definite association but whether the uric acid causes the kidney disease is difficult to tease out. Attempts to show that have shown mixed results.

Four interventional studies have attempted to answer this question in humans:
  • Siu et al. randomized 54 hyperuricemic patients to placebo or enough allopurinol to normalize the hyperuricemia. After a year there was less creatinine progression with the allopurinol.
  • Goicoechea et al. randomized 113 hyperuricemic patients to no therapy or 100 mg of allopurinol for two years. They found improved renal function with drug compared to modest loss of function without allopurinol. And intriguingly they also found a significant reduction in cardiovascular events.
  • Shi et al. evaluated 40 patients with IgA nephropathy for 6 months. This was a negative study with no effect on GFR (but that is hardly surprising given the very short follow-up time), but it did have a beneficial effect on hypertension
  • Momeni et al. performed a 4 month double blind, placebo controlled trial of type 2 diabetics and found a reduction in proteinuria.

From Goicoechea's study of 100 patients
More information can be found on uric acid in my grand-rounds or in an excellent Narrative Review from AJKD.

Despite multiple randomized trials showing allopurinol to be effective in CKD, don't be fooled, both trials were tiny with limited follow-up.
Diameter of the circle is proportional to the trial size

Given that background, it seems well past time to commit to finding a definitive answer to the question of whether we should be using xanthine oxidase inhibitors to slow the progression of chronic kidneys disease.

Scouring I could find only one study that is addressing this hole in our knowledge. The Joslen Center is planning, but has not yet started enrolling, a double-blind, placebo controlled multi-center trial of allopurinol in type 1 diabetics. The study design looks pretty sharp with iothalamate GFRs after 3 yrs of therapy being the primary outcome. However I am dreaming bigger and want my study to apply to all patients, not just type 1 diabetics with nephropathy.

My Dream RCT: methods

My dream study is a placebo controlled, double-blind, multi-center, randomized controlled trial. The study population is CKD stage 3 patients with hyperuricemia (uric acid over 7 mg/dL). This represents a lot of the population with kidney disease which means that the results, if positive, would literally influence the treatment of millions of people. The study will use block randomization and quotas to assure a varied distribution of renal disease. At least a third of the population will have proteinuria and half will have diabetes.

All patients with proteinuria would need to be on RAAS inhibition unless they could not tolerate it. Blood pressure would be treated by the treating physician using JNC8 guidelines. Patients would be randomized to one of three arms:
  • placebo
  • allopurinol 100 mg daily
  • fubuxostat 40 mg daily
If the uric acid remained above 7 after one month of treatment the study drug would be doubled. Patients intolerant to the assigned drug could cross over to the other study drug. Study coordinators would signal a central dispensary that patients were intolerant and the dispensary would change patients on placebo to another placebo (essentially no change at all) and patients on one of the xanthine oxidase inhibitors would cross over to the other xanthine oxidase inhibitor. By employing this three arm approach we will be able to assess if any affects is due to a specific xanthine oxidase inhibitor or a more general effect of lowering the uric acid. It will also allow us to get detailed data on the tolerability and safety of the drugs in CKD.

The primary end-point is a composite of doubling of serum creatinine, death or dialysis.

Secondary endpoints are achieved ambulatory blood pressures, hospitalizations, new cardiovascular events, and gout.

This study would have results applicable to the millions of people with chronic kidney disease and would open up the first novel front in the war on CKD since the wide use of RAAS inhibition.

Apparently this RCT is not a dream but a trial that is going to be done, from Swapnil Hiremath:

Looking through the registry data the CKD-FIX trial sounds like a pretty close match to my Dream RCT, my one concern is they were supposed to begin enrolling patients in March of 2012 but have yet to enroll they''re first patient (according to the registry). Anyone know if this study is still going to happen?

It is on. CKD-FIX to start enrolling next month.

Friday, January 24, 2014

The difference between treatment and prevention

The second twitter journal club a classic article by Rose, Strategy of prevention: lessons from cardiovascular disease. Br Med J 1981 282 pp. 1847-51.

My favorite line:
When ordinary doctors do not accept that responsibility then prevention is taken over (if at all) by uncritical propagandists, by cranks, and by battling commercial interests.
And this, on the treatment of hypertension:
A general practitioner, say, makes a routine measurement of a man's blood pressure and finds it raised. There after both the man and the doctor will say that he "suffers" from high blood pressure. He walked in a healthy man but he walks out a patient, and his new-found status is confirmed by the giving and receiving of tablets. An inappropriate label has been accepted because both public and profession feel that if the man were not a patient the doctor would have no business treating him. In reality the care of the symptomless hypertensive person is preventive medicine, not therapeutics.
A systolic pressure of 160mm Hg may be common at these ages, but common does not mean good.

Remids me of this post from the archives.

Thursday, January 23, 2014

Fix Kidney Wikipedia #fikiWiki

Nephrology is a specialty in crisis. Fewer and fewer internal medicine residents are looking toward nephrology as a viable career. 
The number of applicants continues to plummet. A number of people are looking at ways to increase interest. I'd like to point you to Mark Parker's work with the ASN and Tejas Desai's essay for F1000 (comments on the article). 

One of the solutions that people repeatedly return to is the need for better nephrology mentors for medical students and residents. I, like most people who ultimatly pursued nephrology can point to a great mentor. During my fourth year of medical school, I rotated with Dr Shermine Dabbagh, a pediatric nephrologist at children's hospital of michigan. She was a great teacher and a caring clinician, but she was not my primary influence.

The chief inspiration was not a person at all, it was a book. During my fourth year of medical school, years before I was ready, I read Burton Rose's classic, Clinical Physiology of Acid-Base and Electrolyte Disorders. It is a wonderful book and it absolutely was the inspiration that launched my career.

While the ASN is working on improving mentors, I think the influence of supportive texts like Rose's should not be ignored. There are still great nephrology texts, but unfortunately students no longer use textbooks. They use the web and are increasingly depending on Wikipedia. Unfortunately the Kidney Wikipedia is pretty run down. It doesn't give a reader the impression that the specialty is vibrant, well kept and alive.

Wikipedia is increasingly becoming the initial access point for people to learn about nephrology and we should be better caretakers of it as it is a reflection of our specialty.

I think a great way to revitalize student impression of nephrology is to fix the kidney Wikipedia.
FIx the KIdney WIKIpedia.

Academics scoff at wikipedia, but it will be easier to fix wikipedia than it will be to get a generation of medstudents and residents to stop using it. It is time to stop fighting the Wikipedia and instead we should start refining it, fill it with compelling content that shows off nephrology as the exciting, important and a field that embraces the future of medical education. 

For more information on my opinions about wikipedia check out my editorial at Wing of Zock.

Monday, January 20, 2014

33 Charts Makes it into the National Library of Medicine

Take a look at this post at 33 Charts.

What an honor. I am working on bringing Brian Vartabedian to Kidney Week 2014 to speak about social median in medicine. Looks like I picked the right guy.

Friday, January 10, 2014

Twitter, Nephrology and the next version of the KDIGOmobile App

This summer, through luck and/or moxie I was able to land a plum position on the KDIGO team charged with building the mobile app. The team partnered with the crazy effective nerds at Visible Health to push out our initial vision. Our 1.0 for iPad was launched at ASN Kidney Week in Atlanta. Internally, we described the project as building a bridge across a gorge. This 1.0 is like a piece of dental floss connecting the two sides. It is an important step but it we have big plans for future versions.
We have received a lot of feedback on the initial release and the overwhelming requests are: Android, iPhone, Android, iPhone, Android, iPhone.

We are going to do both, but neither are the next step. The 1.0 version is essentially a PDF reader with all 9 KDIGO guidelines pre-loaded. Moving the app to Android and the iPhone will entail porting all of the guidelines to a new data model. We have a big vision for the product and are reworking the infrastructure to get there. Those two updates will come but they need to wait for the new data structure, for now, the only thing I can tell you is: Patience.

The current version of KDIGO Mobile has a community option that is a ghost town. We are going to tear that down and instead adopt the renal community on Twitter. The new social section will have a number of ways to view twitter that are designed to expose new people to the vibrant nephrology discussions that occur in there.

Users will have a number of twitter channels that they can tune into:

  • Current Twitter users will be able to view their timeline
  • Collecting duct: this is a highly selected list of twitter accounts consisting primarily of professional societies, journals and government organizations (Members | Timeline)
  • Proximal tubule: this is a highly curated list of users that typically provide intelligent nephro-oriented discussion  (Members | Timeline)
  • Glomerulus: this is a general list of every nephrologist and nephrology related organization I could find. (Members | Timeline)
  • Hashtags: this will be one or two hashtags that are of interest to nephrologists. For example, during next years Kidney Week, we would push out #KidneyWk14, during NephMadness we would highlight #NephMadness, We might leave #MedEd, #FOAMed, and #HCSM up at other times. etc.
All of these channels are stored on the servers at Visible Health so they can be controlled remotely and are eternally updatable.

Today, we are asking members of the nephrology social media sphere to look at the lists, try out the timelines, explore the hashtags. Tell us if we missed anyone or added someone undeserving.

When evaluating the timelines keep in mind the goal of these Twitter channels. We want to introduce new users to the utility of twitter for nephrology discussions. The timeline that I am most concerned about is the proximal tubule. The collecting tubule is an official channel and will likely be pretty dry. The glomerulus I think will be too much of a fire hydrant and I am thinking about dropping that channel altogether. I'm hoping that the proximal tubule can have relevant, compelling, content to really show off the utility of Twitter to naive KDIGO users.

Any and all feedback would be appreciated.

Thursday, January 9, 2014


SYMPLICITY-3 was Medtronic's play to get into the hypertension business. They have a device that allows physicians to apply burn the sympathetic nerves of the renal arteries and lower the blood pressure. In a previous randomized trial it worked and SYMPLICITY-3 was what they were going to take to the FDA to get approval.

I started the day with our local hypertension guru explaining the inclusion criteria for Symplicity-4. An hour later this hit the wire:

Full press release
I was a huge fan of renal denervation and a bit of me died when the tweets started flying. Our local Symplicity PI says that the follow-up study with looser enrollment criteria, SYMPLICITY-4, has been cancelled. MedTronic supposedly is still going to carryout a trial of renal artery sympathetic nerve ablation in heart failure. If that is positive then it is possible the field will carry on, but if they abandon that, it may be lights out for the entire concept.

Some thoughts on simplicity 3. The trial was on patients with severe resistant hypertension: office blood pressure over 160 on three blood pressure medications. These are hardcore hypertensives. This may not be an appropriate crucible to test the hypothesis of weather this works.

Thought two is that sympathetic discharge is thought to drive a lot of the hypertension in CKD and ESRD. (See this, this, and most importantly this editorial review)  So maybe when SYMPLICITY-3 excluded patients with GFR's less than 45 they were excluding the very patients where the treatment would be most effective.

Thought three is that maybe in an effort to increase enrollment there were more inexperienced doctors doing the ablation. Unlike renal artery and coronary artery stenting there is no convenient sympathetic nerve ablation analog to TIMI-3 flow. At the end of the procedure the team has no idea if they successfully and adequately ablated the nerves. This could be a confounder. 

It will be interesting in subgroup analysis pif they find a signal pointing to efficacy being related to operator experience or a signal to better efficacy with worse GFR.

I blogged about SYMPLICITY here. Here is what Renal Fellow Network wrote about renal denervation when it was one of the top stories on 2010 and in an insightful post by Matt Sparks

Wednesday, January 8, 2014

Fluid and Electrolyte Curriculum for Residency

I give monthly lectures to the residents at three hospitals. I bill the lectures as a comprehensive, year-long, fluid and electrolyte course. I have never established a fixed curriculum for the lectures, here is one take:
  1. Body water, IV fluids and diuretics
  2. Rapid interpretation of ABGs
  3. Acute Kidney Injury
  4. Osmoregulation and hyponatremia
  5. Hypernatremia
  6. Anion Gap metabolic acidosis
  7. Potassium
  8. Metabolic alkalosis and hypokalemia
  9. Non-anion gap metabolic acidosis
  10. Calcium and phosphorous and metabolic bone disease
  11. Electrolyte emergencies
  12. Board review practice
The curriculum starts with the basic mechanics that interns need to function in the hospital. How to order IVs, and intelligently use diuretics. This includes a review of body fluid compartments so that it is not just practical pearls but is based on physiologic foundation.

Electrolyte emergencies is a lecture that is not entirely written and needs to be. It would be a practical handbook style lecture to walk interns and residents through what I think is the best way to handle: metabolic acidosis and alkalosis, hypo- and hypernatremia, hypo- and hyperkalemia, hypo- and hypermagnasemia, hypo- and  hypercalcemia.

The introductory curriculum ends with the rapid interpretation of ABGs. After that I turn the intensity up a bit and focus on more physiologic based and less practical aspects of electrolytes. This allows deep dives on metabolic acidosis with separate lectures on anion and non-anion gap. I separate out metabolic alkalosis and potassium to provide time to do a deep dive on the monogenic causes of hypertension.

The board review session is a quiz session to review all the concepts of the year.
I have one spare month because a lecture always gets lost along the way.

Kidney TREKS deadline approaches

Kidney TREKS is a program for medical students who want to learn about nephrology. Here are the components of the program from the website:

  • Attend the Mount Desert Island Biologic Laboratories “Origins of Renal Physiology” course for students, June 6-13, 2014. Tuition, travel stipend to Maine, room and board are paid by ASN.
  • Become connected with a nephrologist-mentor who will interact with the student over the course of medical school training, graduate school or postdoctoral fellowship.
  • Attend ASN Kidney Week during the 3rd or 4th year of medical school or graduate school with travel support (as a part of the ASN Program for Students and Residents).
  • Receive complimentary membership to the ASN with access to website resources for students.

To my mind, the first bullet point stands out as a once in a life-time opportunity. Mount Desert Island (by the way, best name ever: it's a mountain, and a desert, and an island. Too bad they couldn't get swamp and archipelago in there somehow) is a research lab where some of the seminal discoveries of renal physiology were made. My understanding is that the students have an opportunity to re-run some of the classic experiments with scientist mentors. Imagine a whole week of Kidney Science Camp.

I have not seen any reviews from participants from last year's KidneyTreks but the reports from the fellow version make me want to re-do fellowship so I can go.

The deadline for applications is January 24th. Get to the link and apply now.

Imagine hiking around this beautiful island after learning the secretes of glomerular filtration.
Mount Desert Island Biologic Lab, home to the world's nerdiest fence.

Tuesday, January 7, 2014


The highest potassium I have ever seen? That would be 15.5 mEq/L.

It's not real. It was pseudohyperkalemia from leukocytosis. The patient had chronic lymphocytic leukemia with a white count of 300,000. If you are not familiar with this condition, check out these posts on Renal Fellow Network: Westervelt and Nate. Nice full text references here and here (pdf).

The pseudohyperkalemia merit badge

The first time I saw this was when I was senior resident. I was sleeping in the call room my pager buzzed. It was the oncology floor with a potassium of 9. The patient had CML and was in a blast crisis. His leukocyte count around 100,000. I immediately suspected pseudohyperkalemia and ordered a whole blood potassium from the ABG lab. It was normal so I went back to sleep. The next morning I received an angry call from the Hemo-Onc fellow. The patient was coding and he was furious that I only ordered an ABG instead of treating the hyperkalemia.

I don't know if the patient coded from hyperkalemia, but I wish that I had gotten out of bed and evaluated the patient. I solved the problem the nurses alerted me to, but if I assessed him, maybe I could of averted an arrest.


Area Codes, RTAs, and Amphetamine. This is what Twitter is like.

This morning I was trying to imagine the mad electrolyte gurus of UT Southwestern in Dallas influencing the naming of the RTAs to match their Area code. Well played Donald Seldin, well played.

Not to be outdone, Dalya Munves joined in the area code and medicine game.

Any other area code-medicine mash-ups out there?

Note. The following 5 paragraphs from Douglas Coupland's Microserfs that I read in 1995 has stayed with me since then. Love this minutia:

"Maybe. But let me digress a bit. Here's something interesting . . . did you know you can figure out how important your state or province was circa 1961 by adding up the code's three digits? Zero equals 10." 
"It's because zeros used to take forever to go around the little rotary dial-while ones zipped along quickest. The lowest possible code, 212, went to the busiest place, New York City. Los Angeles got 213. Alaska got 907. See my point?" 
Karla always comes up with the best digressions. "Yes." 
"Imagine Angie Dickinson in Los Angeles (213) telephoning Suzanne Pleshette in Las Vegas (702) sometime before the Kennedy assassination. She dials the final '2,' breaks a fingernail, and cusses a shit under her breath, irritated at Suzanne for being in a location with a loser area code."

Wednesday, January 1, 2014

2013 the year in review

2013 was a great year for the blog and for social media in nephrology. After a down year in 2012 for PBFluids, only 57 posts all year, I bounced back by nearly doubling that productivity with 112 posts last year. One of my most productive years. But to me the most remarkable change has been the emergence of a nephrology community in social media. My posts here at PBFluids certainly dripped with social media. Here is the year in review month by month.


Only 2 posts. I think the post on some slipshod research on NSAID toxicity in children stand up pretty well. The post included an embedded tweet from leading nephrology tweeter Pascale Lane.


8 posts. The first post is one of my favorite posts of all time. It is an analysis of the ISDA/AHA clinical practice guidelines on enterococcal infective endocarditis. The post is essentially a recap and summary of Twitter conversations on the subject with some additional research to provide some context. The remainder of the month has some solid work, including a post on dialysis for cast nephropathy bemoaning the lack of Gambro 1100 dialyzer availability in the US and a follow-up on the enterococcal post with a deep dive into additional data. Social poked through in a post on the horrible slides provided by the ASN by Myron Miller. I had a nice email from Paul Segal coming to Dr. Miller's defense and a tweet from Jim Smith regarding the post.


March was my most productive month of the year. This was because I was researching NephMadness and working on a review of geriatric fluid and electrolyte issues (don't hold your breath, it was rejected and will not be published). My favorite post of the month is probably this one about the NKF's effort to get dialysis covered under medicare.


April was a very social month. I posted my first Storify (a web service that allows one to easily capture and publish a collection of tweets) on the link between hyponatremia and hip fractures. I had a few posts on Nephmadness (here, here and here). There was a nice post looking at over diagnosis as it relates to breast cancer, prostate cancer and CKD.  I had a patient show up with a potassium of 9 that led to a couple of posts on hyperkalemia. The image of the EKG is one of my most popular tweets ever. I used a poll on managing the hyperkalemia. Another favorite for the year, was a post about nephrology limericks. Again, this was primarily a summary of a twitter conversation.


Another strong month. I tipped my hand about my Kidney Week poster by revealing some of the data on the nephrology blogosphere. My most shared story of the month was on NKFs poorly written story on alcohol and the kidney. PBFluids' blade is still sharp. I had a couple of posts (here, here) on App.GoSoapBox.Com as I tried to incorporate this audience response system into my lecture. And a post with a screen cast on hyponatremia due to SIADH.


June had a number of social posts. I received a lot of commentary on a post about paying for kidney donors. There was some good discussion about my case of rhabdo with a CPK  over a million. But by far the most commented post was about the fool who drank a quart of soy sauce and developed severe hypernatremia. It resulted in two posts and another google docs poll. I also did a nice post on the Central American CKD epidemic that came after I was tweeted about my thoughts on the issue.


July was a light month, as I began to gear up for the second year medical students. I did publish my electrolyte handbook as an eBook. A project that I hope to spend more time on this year.


The big event in August was not on my blog, but on Twitter where I live tweeted the ASN Board Review Class. Awesome experience. I tweeted using the eAJKD account. Unfortunately eAJKD and I were just getting our live tweeting sea legs under us. We missed the important step of compiling the tweets into a blog post. I find that live Tweeting, focuses me and forces me to rework the information into a tweet. This helps me remember the information better. 


I went to London and live tweeted the Med 2.0 conference for eAJKD. Getting better at this. The blog had two posts where I used single tweets as jumping off sites for more extensive coverage, a model that I think best illustrates the purpose of a blog in a Twitter world. The first was on oliguria and the second was on the practice of giving patients money to help them buy medications, or in this case a treadmill.


Only 6 posts but a lot of impact. The month began beating back the idiots suggesting IV contrast is benign to the kidneys. I took the boards that month and posted my thoughts on the test and the ASN Board Review Class. The longest and one of the most important posts of the year was next. I posted on the CJASN electronic journal club. This has been a failure up to now. I hope that in 2014 this project can be re-invigorated. We will see.


I posted on the FDA's terrible decision to deny Tolvaptan for ADPKD, following Bill Brazell's brilliant essay in the Atlantic. We also had some fun guessing the retail price and possible names of the novel potassium binder,  KS-9. I posted on my Kidney Week experience. This was the first time I think Kidney Week really broke through on Twitter with a number of voices. It was a great success. I rounded out the month with an in-depth review of UKidney's well done library of high-impact nephrology articles.


December was dominated by the Renal Fellow Network's annual top nephrology stories of 2013 (see here, here, here, here and here). This turned into a collaborative effort as a lot of independent nephrology bloggers and participant in social media began to blog about different stories. I hope 2014 turns into the year when we really see more collaboration in the Nephrology Social Media Space. I think the RFN top stories offers a blue-print for this. The other post that was particularly social was an examination of an abstract linking Pip/Tazo to acute renal failure. A lot of twitter discussion on this.
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