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.

Update:

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.

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?
Phosphate?
Bicarbonate?
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.

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