Thursday, December 29, 2016

Ad hoc blood pressure lecture

I am attending on the dialysis service in December and the residents requested a lecture on hypertension. This was a sharp group so I decided to do an update on the literature and go through four papers in the session. It went well. We had lots of great discussions and answered a lot questions.

SPRINT. We talked about the impressive results but really focused on the very selective patients population and how it was not consistent with a lot of patients we see in clinic. We also focused on how they assessed blood pressure and how different it is than standard blood pressure assessment.

The next study was HOPE-3 shows that when you apply what you know from SPRINT but use a standard blood pressure assessment and pair it to a less sick population you get a negative result.

Then we looked at PATHWAY-2 to put add some evidence to the question of how should we treat resistant hypertension.

Then we finished with "Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials" a fascinating meta-analysis that looked at dose response curves, and side effects. Really interesting paper. H/T Ricky Turgeon PharmD. The conclusion from the data is that adding additional drug classes at lower than standard doses results in a nice blood pressure improvement with a clean side effect profile.

Other suggestions that didn't make the 40 minute cut:

Treatment of Hypertension in Patients 80 Years of Age or Older

Agree this is an important study.

Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial

I almost feel that a trial that has Atenolol in the control arm is practically a placebo. That drug never reduces events. I think the official tag line is "Atenolol: when all you care about is reducing the number on the dial."
Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus

This is the opposite side of the SPRNT coin. Low blood pressure appeared to be of no benefit and possibly harmful (Table 2). Nice reduction in stroke though (Figure 2). 

A Controlled Trial of Renal Denervation for Resistant Hypertension

The mother of all medical reversals. Great study. Totally upset a runaway freight train of interventions. To me this shows that industry sponsored trials (when designed with the intension of FDA approval) are not marketing shams but can add clarity to medical knowledge.

Why I am going along with the ABIM shakedown

So I received the e-mail telling me it's time to pay the ABIM or I will get the dreaded "not participating in maintenance of certification" addendum to my board certification.

This is horrible. If you make people take a massive high stakes exam to be board certified for the next decade then the ABIM should not effectively revoke that board certification (or at least put it in doubt) because I am not participating in continuing medical education in the way they see fit. I am an adult and can study and maintain my skills as I see fit. Taking, and passing the recertification exam proves I am responsible for my own education. It makes me so angry and it really feels like it is there just as a money grab. Don't tell me that I passed a 10 year recertification exam and then discount your own exam after  couple of years with that damn asterisk.

That said my whole career is built on certification. The privileges of being a doctor are due to a complex interplay of private and public certifications. Much of the edifice of nephrology is based on certification and hospital privileges preventing just any person or even any doctor from providing dialysis. I feel that since I receive so much from these certificates it is a bit hypocritical to pick and choose when I want to participate. I have cast my lot with the certification process so I will continue to participate.

Additionally, even though I have am angered and feel ripped off by the ABIM protection racket, when I try to explain the controversy to non-doctors they don't get it. People put so much trust in doctors and they are rightly terrified of getting a bad one. This is why Top Doctor issues of the local glossy magazine are so popular. People want a good doctor and intuitively know that their ability to recognize quality from personal interactions or or other superficial experiences it limited. People want systematic mechanisms in place to weed out poor ones and make sure all doctors are maintaining a level competency. Unfortunately, I feel that ABIM is not a good mechanism for this aim. But people are naturally suspicious when they hear that doctors are complaining about how onerous a certification process is. I think their first inclination is, "Yes! Hold those doctors to task." And while physicians fret about the nightmare that occurs to individuals that fail to maintain their board certification, the public feels the opposite, and are thankful that somebody is at the wheel trying to maintain the quality of the physician workforce.

So I am going to pay my pound of flesh and continue to work with ABIM to reform the system rather than leave it entirely.


Imagine if a year or two after graduating college, you get a letter from your alma mater telling you, that even though you completed all of the coursework and payed all the tuition bills, everytime someone inquires into if you actually graduated they were going to tell them "Yeah, but we don't think he is so serious about maintaining his skills and have reason to doubt his commitment." We would be happy to change this message to simply "Yes, he graduated" if you pay us $353.00 every year. It sure would be a shame not to get full credit for all the work you've done getting that degree, and compared to how much money you earn because of the degree, $353 is just not that much money."

I remember feeling screwed that my board certification, unlike people just a few years older than me, would require constant recertification. Ten years between board exams is not too onerous, but then after that they made the deal worse still, and now I need to recertify every ten years and pay them yearly, so ABIM doesn't smear my name in the public.

Maybe I should just pray they don't alter the deal any further.

Update. Even better video:

Wednesday, December 28, 2016

The pioneering generation of nephrologist is dying

Larry Fleischman, a pediatric nephrologist, and pioneer in dialyzing children has passed.

Larry was always a positive role model for me when I was a medical student.

Tuesday, December 27, 2016

Diuretic Infographics

For the second time I in the last month I was looking for these graphics n PBFluids and for the second time I couldn't find them. I was sure I had posted them, but I hadn't.

So here are my loop and thiazide diuretic infographics. Enjoy.

Monday, December 19, 2016

Nephrogenic diabetes insipidus and carbonic anhydrase inhibitors

Nephrogenic diabetes insipidus (NDI) is incredibly difficult and frustrating to treat. If the cause of NDI is loop diuretics, hypokalemia or hypercalcemia, it is a trivial problem, however in patients with congenital NDI or lithium induced NDI the treatment options are limited and pretty ineffective. The standard game plan is administering thiazide-type diuretics paired with a low salt/low solute diet. Here is the page from The Companion:
I think the first question is one of my favorites in the entire book.

Recently there has been some noise that carbonic anhydrase inhibitors maybe the way to go in lithium induced NDI.

Lithum causes NDI in two stages. In the first stage, lithum induces a down-regulation of the aquaporin-2 channels. The second stage comes from loss of the aquaporin-2 expressing principal cells of the collecting duct. To compensate there is an increase of alpha-intercalated cells.

The theory that HCTZ improves NDI through volume deficiency first took a hit in 2014 when Anne Sinke, and company showed that mice with lithium induced NDI but without the thiazide sensitive sodium-chloride co-transporter (NCCT) could still reduce urine volume in response to thiazide diuretics.

Let that sink in for a moment...mice that do not have the thiazide sensitive NCCT respond to thiazides as expected in regards to lithium induced NDI. This finding required an explanation and the authors suggested that this could be due to the carbonic anhydrase activity of thiazide diuretics. 

Yes, I know that thiazides reliably cause metabolic alkalosis, but despite that they have some minimal carbonic anhydrase activity that is uncovered in the NCCT knockout mice. According to this site, thiazides were initially designed to be carbonic anhydrase inhibitors, and then found to have NCCT antagonism activity. (Fun fact if you ask google about the thiazide's effect on carbonic anhydrase the top hit is from David Goldfarb (@Weddellite) back from his basic science days.)

Back to the carbonic anhydrase story. Carbonic anhydrase is critical for bicarbonate reabsorption in the proximal tubule because it allows hydrogen secreted by the Na-H exchanger to combine with filtered bicarbonate to form CO2 and water. The CO2 is able to freely able to enter the proximal tubule cell where it combines with a hydroxyl group to reform bicarbonate. 
The authors concluded that by blocking carbonic anhydrase, there was less sodium reabsorption in the proximal tubule leading to activation of tubular glomerular feedback lowering GFR.
This lead to a second series of experiments where the same team reproduced the same reduction in urine volume but this time with acetazolamide, rather than HCTZ. The authors also thought there was a second mechanism based on acetazolamide's ability to decrease lithium entry into principal cells of the collecting duct (similar to amiloride) and/or a reduction in intra-renal prostaglandin synthesis.

Fast forward to November 2016 and we have an interesting letter in the NEJM regarding a human patient with NDI that was admitted for a craniotomy. Post-operatively he developed recalcitrant hypernatremia with severe polyuria rising to 12 liters a day. 

...we administered acetazolamide to a patient with severe lithium-induced nephrogenic diabetes insipidus that was resistant to hydrochlorothiazide treatment and other measures...

The team used 500 mg of acetazolamide bid to take his urine output from ridiculous to merely absurd. Compelling data.

Thursday, December 8, 2016

What does a medical student do when they have a renal question? Introducing #AskRenal

Yesterday's post and interaction has been bouncing around my skull all day. First of all I was blown away by the discussion generated by the simple question of "What does aldosterone do?"

And then I started to think about the possibilities. I imagine that Niaree has a lot of friends with nephrology questions. And I have a lot of friends that are nephrology nerds just bubbling with answers.

I'm thinking if there was a hashtag that could be used by medical students struggling with renal phys and renal pathophys that resulted in an immediate answer from nephrologists all over the world we could leverage the always-on nature of Twitter to demystify the black box that is the kidney.

Plus getting the pulse on the questions that keep hanging medical students will make us all better teachers.

So why don't we try this. 

Medical students brings us your confusion, your riddles, your frustrations with renal. Your mass of ambiguity yearning for clarity. Throw off your darkness for enlightenment. #AskRenal is here to clarify your journey.

Wednesday, December 7, 2016

No Salt Humans

Great Twitter moment tonight when a medical student confessed ignorance of aldosterone and an aldosterone basic scientist piped in with what he finds beautiful about aldosterone.

I had no idea what Yanomami man was but Brian was right there:

So the paper is available for free here and it shows a kidney homeostatic system performing in ways that I would have guessed were impossible.

A 24-hour urine sodium of 1 mmol. No fricken way!

I give you table 4:

Anybody want to hazard a guess at what the giant unmeasured anion in the urine is?
Probably bicarb, especially when you take a gander at their aldo levels:

I wonder if these indians suffered from all of the ill effects of aldosterone thrown about?

Monday, December 5, 2016

Treating mild hyperkalemia

Somewhere along the road to becoming a doctor med students develop the hyperkalemia insulin reflex. See an elevated potassium give 10 units of IV insulin and 25 grams of D50. Yesterday I saw this done for a potassium of 5.6.

No. One. Dies. From. A. Potassium. Of. 5.6.

But there is morbidity from the insulin glucose antidote.

These guys from Rush University Medical Center looked at the risk of hypoglycemia from the standard 10 units of insulin followed by 25 grams of glucose. They found 13% of ESRD patients developed a glucose south of 60 mg/dl.

Remember the kidney both metabolizes insulin and is a source gluconeogenesis, so dialysis patients are naturally more prone to hypoglycemia.

 Love me some table one.
The patients that developed hypoglycemia were less likely to be diabetic, and had a lower glucose. In response to this study the authors suggested an alternative regimen of increased glucose monitoring and an additional 25 grams of dextrose:

Similar data was found in a study by Schafers. Schafers followed that study with this one, which suggests that weight based insulin dosing 0.1 units/kg up to 10 units could reduce hypoglycemia by about half:

What is truly terrifying is if some people start trying to really drive the potassium down with Sterns' recommendations from KI:

Also good factoid, there is less hypoglycemia if you add albuterol to insulin and glucose.

Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects

Let's be careful out there and stop treating inconsequential hyperkalemia, let's save our toxic antidote for truly toxic potassiums.

Friday, November 25, 2016

When a non-clinician tells you AKI is simple, prepare for disappointment.

Acute kidney injury (AKI) is hard.

Things that seem like they should work often don't. Just ask Perry Wilson.

And even the most predictable cases of AKI are resistant to intervention. Look at bypass surgery. We know days in advance the time and place the AKI will occur and despite that foreknowledge, like Cassandra, we are powerless to prevent the AKI. Same with contrast administration (or not). Same with AAA surgery. We have been unable to meaningfully reduce the rate of AKI in any clinical circumstance.

AKI is a tough nut to crack.

So when I read about this guy, Mustafa Suleyman (Twitter), telling the public that,
"There are around 1,000 people a month dying needlessly. This is a huge hidden killer. It costs more than breast cancer care in the UK and [AKI] is super simple to prevent." 
I'm insulted, like we must be idiots that we haven't fixed this yet. And thank-god the computer scientists are here from Google to finally cure AKI for us.

Turns out the National Health Service is implementing a system at The Royal free Hospital to speed alerts to doctors so they can react quickly to signals of acute kidney injury. The headlines being generated from this project are amazing:

The company providing artificial intelligence is DeepMind, a Google company. The product that detects AKI early enough to avoid it is Streams.

Maybe we should excuse the visionary of an artificial intelligence company. The medical director of the Royal Free should be a bit less grandiose and more evidence based. What did he have to say?
Stephen Powis, medical director at the Royal Free said, “We know that a quarter of deaths from acute kidney injury are preventable if clinicians are able to intervene earlier and more effectively.”
Boy, that sounds like data that comes from an interventional trial where warnings were given to some clinicians and others did not receive them and the RR for AKI was 0.75. Unfortunately, this study has never been done. When a similar study was done by Perry Wilson they found no effect at all from early warnings. When I asked Med Twitter if they knew where this data came from I was given a few old retrospective trials.

Nothing prospective. Nothing to justify the certainty of Dr. Powis. The 25% comes from a report produced by NCEPOD called Adding Insult to Injury. The report attempted to analyze all of the deaths for 3 months in 2007 due to AKI. They failed to capture surgical patients and they did not get the records on 40% of the cases they requested.

As part of this examination of the failures they asked experts that reviewed the case files if the AKI was avoidable and they said yes it was in 14% of the cases. I'm sorry, but the distance between a reviewer believing an episode is avoidable and an AKI case actually being avoidable is more than a casual step, let's call it a major leap. Remember that reviewers were only reviewing patients with mortal outcomes. Given that, the reviewers knew of the subpar outcome, I'm not surprised the reviewers found lots of substandard care:
Maybe I am jumping the gun and the Deep Mind notification system, Streams has been prospectively vetted and shown to improve outcomes. I also concede that it is likely that the system can improve the number of AKIs but that isn't and shouldn't be the sole goal of the system. AKI is an intermediate outcome. The system should be judged on its ability to reduce mortality and here I am skeptical. I suspect the AKIs that are simple to avoid are not the ones driving the high mortality levels.

I believe the Deep Mind people have this type of model of AKI:
In this model, all the different etiologies of AKI feed into a single pool of undifferentiated AKI and measures that reduce the incidence of any of the causes of AKI will reduce the fraction of patients that die of AKI.

I think the correct model of AKI is more like this:
In this model each etiology of AKI leads to mortality in it's own lane. So changes in the incidence of AKI from volume depletion can only reduce the already low mortality from that cause of AKI.

I look forward to seeing the results of this project and hope that they are measuring the outcomes and plan to publish their prospective and interventional data.

Confirmation bias, cognitive dissonance, and contrast nephropathy

I have been following the research of McDonald which repeatedly showed no signal of contrast nephropathy when looking at large databases.
Controlled contrast medium-induced nephropathy studies demonstrate a similar incidence of AKI, dialysis, and death between the contrast medium group and control group.
This was just a curiousity that felt like the work of magician because no matter how many different ways that McDonald et al tried to prove there was no contrast nephropathy, I had seen it with my own eyes. I had seen young people with a normal creatinine who were completely stable go for a contrasted CT scan and then spiral into renal failure in subsequent days. No one could convince me that this was incidental renal failure. Renal failure just doesn't happen like that.

The best I could do to explain away the work of McDonald was to say that she is a radiologist so it must be biased in favor of her procedure/specialty. I know this is weak sauce but the I had seen it with my own eyes could not be silenced. Then Chertow. Here was the most prominent nephrology clinical trialist of our time coming to the exact same conclusions as the radiologists.
...the incremental risk of AKI that can be attributed to radiocontrast is modest at worst, and almost certainly over- estimated by patients, physicians, surgeons, radiologists, and other decision-makers.
I have been trying to reconcile this cognitive dissonance and this is where I am. The decision to use changes in creatinine to define contrast nephropathy results in a definition that captures lots of false positives.
Definition of contrast-induced nephropathy (CIN): impairment of renal function defined as either a 25% increase in serum creatinine (SCr) from baseline or 0.5 mg/dL (44 µmol/L) increase in absolute value, within 48-72 hours of intravenous contrast administration.
Note that unlike definitions of other entities like hepatorenal syndrome, there is no exception if there is alternative explanation for the renal failure. Any patient with sepsis, hypotension, and a complete breakfast of aminoglycosides, ketorolac, and ramipril that happens to get a contrasted CT scan followed by a bump in the creatinine is another case of contrast nephropathy. Though being admirably sensitive, this definition is wildly non-specific.

So the key question in evaluating the definition of contrast nephropathy is what proportion of cases are real cases of contrast nephropathy and what numbers are incidental AKI that happen to occur after contrast exposure. In other words how many of those contrast nephropathies are false postives. To reconcile my experience and Chertow’s data I have shifted my position from being mostly true positives with a small amount of noise to mostly noise with only a few cases of true contrast nephropathy.

Once you accept that the the majority of cases of contrast nephropathy are just incidental cases of AKI, other facts start to come into focus. For example, look at the risk factors for contrast nephropathy:
  • CKD
  • Diabetes mellitus
  • Advanced age
  • High contrast dose
  • NSAIDs
  • ACEi
  • Heart failure
  • Balloon pump
  • Volume depletion
  • Hypotension
  • Shock
How many of those are also risk factors for AKI in general? Outside of contrast dose, I’d say all of them.

How about the interventions we do to reduce contrast nephropathy:
  • Avoid diuretics
  • Avoid NSAIDs
  • Stop ACEi/ARBs
  • Give IVF (and 0.9 NS is better than 0.45 NS)
This looks like a pretty good recipe for avoiding AKI in general.

Why is this important? Well for one I think our research is lying to us. I have been surprised on multiple occasions that the patients that get contrast nephropathy don’t fit the model of the high risk patient and likewise patients that are set-ups to get contrast nephropathy don’t. Our models are so overwelmed with incidental AKI that they do not give us a good idea of the people who are truly at risk of real contrast nephropathy.

I wonder, if we were to do a careful analysis of contrast nephropathy cases where we excluded every case that could have an alternative explanation of AKI, to produce a cohort of people with a very low rate of false positives. How different would the risk factors for contrast nephropathy look like in that cohort? I suspect contrast nephropathy would look more like an idiopathic condition.

Friday, September 2, 2016

Question from OUWB M2 on SIADH

Another question from the e-mail
I am trying to understand why SIADH does not cause edema. I understand that in SIADH, there is an increase in Total Body Water, as the increased ADH causes increased water reabsorption. However, there is no change in total body sodium. This implies that the issue is a euvolemic hyponatremia. I would imagine that with total body water increase, there is increased ECF and therefore increased capillary hydrostatic pressure. How come this doesn't result in edema?
This is a question I get every year.

The question comes from a student with clear thinking about SIADH. And it is true that careful and precise measurements of total body water will show that people with SIADH have excess total body water, so they are not truly "euvolemic." But we use the term euvolemia here because they are in sodium balance. Their sodium intake equals their sodium excretion:

This is very different than patients with hypervolemic hyponatremia (heart failure and liver failure) where sodium intake is much greater than sodium excretion. With positive sodium balance (total body sodium increases everyday) heart failure patients develop progressive and clinically evident edema.

The other way to look at the increased water that patients have with SIADH is to quantify it. If a patient with SIADH drops their sodium from 140 to 120 they have dropped there sodium by 14%. This comes from an increase in total body water of 14%, so in a 70 kg young man (42 liters total body water), this represents a increase in total body water of 5.88 liters. Two thirds of this water would be intracellular, so only 2 liters would be extracellular. In heart failure, dogma states people gain 5 kilograms of body weight before they develop clinically evident edema. Since the edema is from excess sodium all of this fluid gain is extracellular. So the amount of water that needs to be retained to lower the sodium 20 points, is less than half the amount that is needed to cause clinically evident edema.

Question from OUWB M2s on potassium excretion

Here is the question:
Regarding potassium secretion, I'm having a little trouble understanding one concept: increased flow rates with the collecting tubules results in increased potassium secretion. Say a person is on a loop diuretic and their flow rates are increased. I understand that increasing sodium delivery will result in more potassium secretion, but how does the flow rate affect it? 
I would've guessed high flow rates would decrease sodium re-absorption and therefore decrease potassium secretions.

My answer was just a figure from The Fluid and Electrolyte Acid Base Companion:

  The idea is that increased tubular flow has two interrelated explanations for why it increases potassium excretion. 
  1. The first is that when potassium excreted by either the ROMK or Big K channel, potassium in the tubule then will decrease the chemical gradient from in the cell to out of the cell. By increasing the tubular  flow potassium is quickly washed away, maintaining (or refreshing) the chemical gradient. 
  2. The second is that increased tubular flow is really synonymous with increased sodium delivery. This sodium is then sucked up by the eNaC allowing the generation of the electronegative tubule increasing the excretion of potassium.

Top Tweets from the last year

The Twitter analytics page is just an amazing trip down the memory hole. If you haven't checked it out, do so. Some highlights from the last year:




June runner-up


May runner-up



March runner-up



January runner-up


Monday, August 22, 2016

Question from the OUWB M2s

This question came via e-mail:
A couple of my classmates and I had a question regarding one of your slides (slide 39 on the Potassium, Metabolic Alkalosis presentation). We were unsure of the mechanisms that prevented bicarbonate excretion with hypokalemia, specifically decreased NaK2Cl activity in the loop of Henle and decreased NaCl resorption in the distal convoluted tubule. Could you please give us an explanation for these mechanisms?
So the reason you can't remember a mechanism is I gave the old "just because" mechanism without much explanation.

The first step of why the the Na-K-2Cl transporter slows own in response to a low K is pretty sraight forward. Tubular potassium will fall as patients get hypokalemia. As the plasma potassium falls, less and potassium is filtered and then less potassium will be available to cycle the Na-K-2Cl pumps. The decreased activity in the loop of Henle results in more distal delivery of sodium and that drives move acid secretion and maintenance of the metabolic alkalosis.

The distal convoluted tubule is a bit more complex. Here is a diagram:

The hypokalemia stimulates the hydrogen-potassium exchanger. This generates intracellular acidosis, even though the patient has alkalosis. In order to correct the acidosis the cell slows sodium-chloride co transport so more sodium washes down stream and stimulates the hydrogen secretion, maintaining the alkalosis.

If you are looking for a deeper dive into metabolic alkalosis I recommend this review by Galla in JASN

Wednesday, August 10, 2016

OUWB Resources 2016

Here is the PDF of today's Acid-Base Workshop

There is a typo on slide 111 of the the acid-base lecture:

here is the correct table. Sorry.

8 AM Tuesday lecture

Potassium metabolic alkalosis and hypertension:

Introduction to potassium lecture:


part 1:

part 2:
Greatest Potassium Lecture Ever...part 2 from joel topf on Vimeo.

Part 3:
Greatest Potassium Lecture Ever...part 3 from joel topf on Vimeo.

Monday's Lecture:

  • Introduction to Acid Base, deep dive into metabolic acidosis (keynote | PDF)

Wednesday's lecture in Keynote format

The reading material for the TBL

More links to be added shortly.

Monday, July 18, 2016

My talk on the evolution of the medical textbook and the role of social media

One of the most exciting thing I have ever done was speak at dotMed this past February. I blogged about it. My talk just got pushed out to youtube.

The idea underlying the talk is that the medical textbook holds a central role in the education of physicians. Over the years, the textbook evolved from a single author text like Osler's to the multi-author textbook like Harrison's, to the online, digital solution like UpToDate.

I speculate that the next evolution will incorporate mobile and social elements and then proceed to show how the nephrology social media collective is using social tools to deliver compelling medical education. Enjoy.

Wednesday, June 8, 2016

Two new lectures: diabetic kidney disease and mild hyperkaemia

Diabetic kidney disease


The survey on the treatment of mild hyperkalemia:

Results of the survey:

Sunday, June 5, 2016

Can you answer this question on mild hyperkalemia

I am giving a new lecture on hyperkalemia. I want to start with a question on how people manage mild hyperkalemia.

Here are the two slides:

If you could answer the survey and make suggestions for improvements I would appreciate it. Tweet suggestions to @Kidney_Boy.

Tuesday, May 17, 2016

Seminal Articles in Health Policy

So this is a little out of my wheelhouse, but yesterday this tweet came across my tweet stream:

Ari Friedman replied

Which was simultaneously a great answer and kind of useless. He then sent me a bibliography, here is his list with links:

  1. Arrow K. Uncertainty and the Welfare Economics of Medical Care. 1963;53(5). (PDF)
  2. Pauly M. The economics of moral hazard: comment. American Economic Review 1968;58(3):531–7.  (PDF)
  3. Cutler DM, Reber S. Paying For Health Insurance: The Trade-Off Between Competition And Adverse Selection. The Quarterly Journal of Economics 1998. (PDF)
  4. Taubman SL, Allen HL, Wright BJ, Baicker K, Finkelstein AN. Medicaid Increases Emergency-Department Use: Evidence from Oregon’s Health Insurance Experiment. Science 2014;343(6168):263–8.  (PDF)
  5. Cohen JT, Neumann PJ, Weinstein MC. Does Preventive Care Save Money? Health Economics and the Presidential Candidates. N Engl J Med 2008;358(7):661–3.  (PDF | NEJM)
  6. Burns LR, Pauly MV. Accountable Care Organizations May Have Difficulty Avoiding The Failures Of Integrated Delivery Networks Of The 1990s. Health Aff 2012;31(11):2407–16. (PDF)
Cedric Dark tweeted:

I will add to this when he gets back to me.

Wednesday, May 11, 2016

Do you give a Flux about Flux?

There is a spirited debate in our hospital system about the use and availability of high flux membranes. Part of the debate centered around middle molecule clearance and its relationship to uremia. I fell back to my old standard the HEMO trial.
A study as long and as expensive as HEMO will not be let to rot after its first paper, and the research parasites extracted a number of tantalizing findings. In 2003 JASN published an analysis that looked at flux when patients were divided by vintage. Dialysis patients who have been on dialysis for more than 3.7 years had improved outcomes with high flux dialyzers:
In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of all cause mortolity (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis.

Though the data is not so compelling when the vintage is divided by quintiles:

Even more damning ,was the fact that the longer the patients were randomized, the smaller the effect of high flux membranes:

Longer years of follow-up should show more protection from high-flux membranes (lower RR in the table) but the opposite is actually seen.

Additional post-hoc analysis was done here, showing decreased cerebrovascular disease for longer vintage patients:

I then came across the membrane permeability outcome study, MPO, published in 2009 in JASN. This European study was designed to answer the following question:
This prospective, randomized Membrane Permeability Outcome (MPO) study was designed to compare the impact of membrane permeability on survival in incident HD patients who had either low ( 4 g/dl) or normal albumin ( 4 g/dl) and were treated with a minimum dialysis dose (single-pool Kt/V [spKt/V]) of 1.2. 

Use of incident patients will eliminate the vintage advantage seen in the two post-hoc HEMO studies discussed above. Separating patients based on albumin at baseline seems a bit wonky. Lots of patients have low albumin at the start of dialysis. And I doubt there is an inherent biological reason for this. Turns out, the two tiers were due to pokey enrollment after 11 months and they changed enrollment rules.  They also changed the rules by extending the time patients could take to get to a spKt/V from 1 month to 3 months. The things we do for enrollment!

The top-line results showed no difference in survival by flux:

But when the authors looked at the pre-specified sub-group analysis for patients with a baseline albumin less than 4, the data showed protection with high-flux membranes:
This isn't just any pre-specified sub-group, this was supposed to be the entire cohort, and only became a sub-group after they amended the protocol.
They also found an interaction between flux and diabetes. This was post-hoc analysis:

So, in the end this seems like a tale told by an idiot (your truly), full of sound and fury signifying nothing because we have all moved on to high flux dialyzers, except in the hospital where F16 low flux dialyzers are available and cheaper than their high flux brethren.

My concerns with the wearable artificial kidney

Last week the Wearable Artificial Kidney reached some sort of new benchmark and a bunch of press ensued. I stumbled across this one.

And I tweeted:

This was a popular tweet 

but not a popular opinion. Most people say that it is great to see out of the box thinking in nephrology. They advised me not to look at the technology as it is today but envision where this technology could go.

I appreciate the technology and can totally see how something like this:

Could undergo a transition analogous to this:

My concern is not the size of the equipment, though by the looks of it, they still have a formidable chasm to cross. My concern has to do with access. This is hemodialysis. It still needs a way to get blood out of the body, into the machine, and back into the body, reliably, continuously and safely. This is not a trivial task and tunneled catheters have a high rate of infection and mortality. 

Persons using catheters had increased risk of all-cause mortality (RR=1.38, 95% CI=1.25–1.52), fatal (RR=1.49, 95% CI=1.15–1.93) and nonfatal (RR=2.78, 95% CI=1.80–4.29) infection, cardiovascular event (RR=1.26, 95% CI=1.11– 1.43), and hospitalization (RR=1.51, 95% CI=1.30–1.75) compared with those individuals using grafts. From Ravani, JASN 24:465-73, 2013.

They are public enemy number one in dialysis units and this technology depends on them. Vascular access is the weak link of hemodialysis, whether it is in-center, home or a WAK. And adding mobility, continuous use, and patient error to the equation probably will not help.

I look forward to sheepishly reading this post one day in our WAK future, but I suspect that future is populated by hover boards and self tieing shoes.

Thursday, April 28, 2016

Come to the NKF Spring Clinical Meeting social media workshop

Today at noon.

We will try to Periscope this session, depending on wifi bandwidth.
Lunch is provided for a small charge. Space is limited, but we still have seats left.

Saturday, April 2, 2016

The math behind the P value

Great post on the P value including detailed analysis of the math behind the calculation. This is what I love about the internet.

Related Posts Plugin for WordPress, Blogger...