Posts

Posted on

Noon conference St John Macomb: Renal Adventures in Imaging

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.
It is a lecture on three issues in nephrology that are not normally put together in a single lecture:
  1. Phosphate nephropathy
  2. Nephrogenic fibrosing dermopathy (I’ll never get used to calling it nephrogenic systemic fibrosis because, despite what the literature states, all five patients I have seen had purely dermatologic manifestations)
  3. Contrast nephropathy
I like the lecture because it is not a typical nephrology lecture. 
I gave the lecture Seder-style and had crammed for the last three days getting the booklet ready. It’s the longest booklet by one sheet (32 pages rather than my standard 28). It turned out pretty good, though the acetylcysteine section needs to be built up and I need to comb through it for typos.
Posted on

Just spent 15 minutes getting better at PubMed

This is time that will pay major dividends down the road.

The mayo clinic libraries have posted a series of screencasts that will make you better at PubMed. Spend the time.

https://videopress.com/v/wp-content/plugins/video/flvplayer.swf?ver=1.18

https://videopress.com/v/wp-content/plugins/video/flvplayer.swf?ver=1.18

Posted on

iPad: the delivery on a 14 year old pledge

In 1996, a year before returning to Apple, Fortune interviewed Steve Jobs. When asked what he would do to save Apple he explained:

If I were running Apple, I would milk the Macintosh for all it’s worth — and get busy on the next great thing. The PC wars are over. Done. Microsoft won a long time ago.

At that time, this quote was like a dagger in my heart. At the time Apple was flailing. Windows was rocking and the drumbeat of the end was getting louder. To hear the creator of the Mac declaring the war lost was heart breaking. I chalked it up to an off-the-cuff, spoiled-grape quotation.

Later, after Steve came back to Apple I began to feel vindicated in my opinion. Steve didn’t act like he was “milking the Macintosh.” In no way could I see his actions as just “milking the Mac.” Check out this video of Steve at the 1997 MacWorld. I see no indication of the hopelessness that the PC wars were over (Steve enters at 5:30):

So from the moment Steve re-enters the PC picture, he restokes the PC wars. He introduces the iMac. He successfully recreates the NeXT operating system as OS X. And, though he had phenomenal success growing Apple’s computer business, none of that really fits the bill of The Next Insanely Great Thing.

When the iPod came out in late 2001 I wondered if this was the next great thing, but music, no matter how cool, was just too small a stage for the man who had twice revolutionized computers. Also when you look at the history of the iPod it wasn’t an Apple idea, rather, the concept was brought to Apple by Steve Fadell after Real passed on it. It didn’t feel like what steve meant by “getting busy on the next great thing.”
What the iPod did do, is demonstrate that Apple could win in consumer electronics. This time after Apple innovated the followers at Sony, Microsoft and Dell couldn’t overtake’em. The disaster which nearly destroyed Apple in the PC wars wasn’t re-run during the digital music revolution. Apple invented the digital music business and ten years later the story is still only about Apple.

When the iPhone was introduced this felt like the The Next Big Thing. Phones are ubiquitous and important. The shift to mobile computing has been a long standing theme in the computer industry. Smart Phones aren’t just about smarter phones but putting the power of the computer in your pocket. So it was clear that the iPhone fit the bill of the “the next great thing” but what wasn’t clear was that it would replace the Macintosh. 
With the introduction of the iPad I am now convinced that it will replace the Mac. The two pieces of data that convinced me of this was the demonstration of the iWork for iPad and the support for real keyboards. Both of those mean that the iPad is not just a media consumption device but also a media creation device. Congratulations Steve, I hope the iPad represents the next revolution in computing.
Posted on

Marathon running is bad for your heart? Say it isn’t so!

I am an avid recreational runner. I am just about to come up on my 2 year anniversary of being a pretty regular runner, see Operation: Marathon. So it was pretty disturbing to see these two abstracts getting press form the 2010 American College of Cardiology:

  1. Researchers have shown that long-term marathon runners, those who have completed at least 25 marathons over the past 25 years, have increased coronary calcium and calcified plaque volume.
  2. A second group did a study which suggested that marathon runners had increased aortic stiffness compared with individuals who exercised recreationally
I would really like to stress that both of these studies do not look at patient oriented endpoints but intermediate end-points. I would hesitate to turn anyone off of exercise, which I tell my patients is the closest thing we have to a fountain of youth, until we had data containing hard end-points.
To corroborate that, the first study looked at a number of other cardiovascular risk factors, and all of these pointed to improved cardiovascular risk profiles:
  • lower heart rate
  • lower body weight
  • lower BMI
  • Higher HDL-cholesterol levels
The press release is at this link, but you will need to register to get to the meat.
Posted on

Aldosterone escape versus Aldosterone breakthrough

Fluid and electrolyte deity, Robert Schrier,  had an interesting editorial in Feburary’s Nature Reviews: Nephrology (yes, I’ve gotten a little behind in this blogging business).

Escape versus breakthrough refere to completely different and unrelated concepts related to aldosterone.

  • Aldosterone breakthrough occurs following administration of an ACEi or ARB. ACEi block the conversion of angiotensin I to angiotensin II. The decrease in angiotensin II lowers aldosterone. Angiotensin receptor blockers prevent angiotensis II from from binding receptors through out the vasculature but including the adrenal gland where it prevents aldosterone release. At least that is the plan. In reality about 30-40% of patients given ACEi or ARBs have only a temporary decrease in aldosterone and then after a few weeks, aldosterone returns to pre-treatment levels.  

  • Aldosterone escape is a physiologic phenomenon that occurs with hyperaldosteronism. Aldosterone initially decreases urinary sodium increasing sodium retension contributing to hypertension. This does not result in edema because the sodium retention is short lived. After a short time urinary sodium returns to normal through a process called aldosterone escape. There are two processes that account for this:

    1. Pressure natriuresis. Increased blood pressure decreases distal sodium resorption. The exact mechanism of pressure natriuresis is unknown, it is thought to be mediated by hydrostatic forces. Increased blood pressure is transmitted to the peritubular capillaries, so the resorption of solutes must overcome an elevated hydrostatic pressure gradient. In the face of this increased gradient, sodium resorption falls.
    2. Decreased proximal sodium resorption. Volume expansion decreases proximal sodium reabsorption and increases sodium delivery to the distal nephron and overwelms the aldosterone induced sodium resorption.

The implications of aldosterone escape is that primary hyperaldosteronism does not cause edema. It also explains the delay in hypokalemia found with primary hyperaldosteronism. Aldosterone stimulates potassium excretion but hypokalemia is a late finding in primary hyperaldosteronism. The increased potassium excretion occurs with aldosterone escape when the increased sodium delivery (decreased proximal absorption, i.e. escape) occurs with the increased aldosterone levels.

Posted on

Unmatch Day 2010

The worst day in medical school. If you don’t match you get contacted that you need to scramble for a spot. ugghh. Scramble starts tomorrow at noon. Its high stake musical chairs. Hope everyone finds a seat. 
Best day of med school just around the corner on March 18th at noon EDT.

Are any PBfluid readers fourth year med students? Where did you match? Leave a comment.

Posted on

Randomized clinical trial of calcium supplementation

Are Calcium supplements good for you?

Maybe not. This article from 2008 shows increased cardiovascular events in woman randomized to calcium supplementation. I had my mom stop her calcium supplement.

women were included in the study if they had been postmenopausal for more than five years, were aged 55 or more, and had a life expectancy of more than five years. We excluded women who were receiving treatment for osteoporosis or taking calcium supplements; those with an other major ongoing disease including hepatic, renal, or thyroid dysfunction, malignancy, or metabolic bone disease; and those with serum 25-hydroxyvitamin D levels less than 25 nmol/l.

Patients were then randomized to a gram of elemental calcium, as calcium citrate as Citracal or matched placebo.

The results were surprising.
Its amazing the study reached clinical significance given the small size of the trial, only 1,400 patients.
A much larger study, The Women’s Health Initiative randomized 36.282 patients to 500 mg of elemental calcium. They just missed significance for the composite outcome of Myocardial infarction/CHD death/CABG/PCI with a confidence interval of 0.99-1.19.
There might be some signal there.
Posted on

Kayexalate: risks and benefits

When I was a fellow I got an opportunity to write the chapter in Intensive Care in Nephrology on Disorders of Potassium Homeostasis.

Dr. Murray, the editor and my fellowship program director, told me that I couldn’t use review articles or text books as references. It was a golden experience. I systematically went through all of the pearls I had collected on potassium and drilled down to the original data.

The primary conclusion I had after months of exploring the stacks of The Crerar was that the wall of knowledge that I had assumed backed up all of our clinical practices was more like a chain link fence with isolated points of solidity but mostly holes. Science could provide a rough outline but too much of medicine is based on conjecture and reasoned guesses.

One of my finds was the near total lack of data showing cation-exchange resins to be effective. In the chapter I wrote:

…Two recent studies have questioned the effectiveness of SPS [sodium polysterene] resins, but until larger studies corroborate these findings, SPS resins remain part of the therapy for acute hyperkalemia. (106, 122, PDF) SPS and sorbitol usage have rarely been associated with intestinal necrosis; whether this is due to sorbital, the resin, or other factors is unclear. (123, 124, 125)

The key table from the Gruy-Kappal article showing the lack of effectiveness of SPS resins

This was actually the revised paragraph. The first draft was much stronger. I railed against the use of kayexylate given the lack demonstrated benefit and the emerging data on the dangers of this medication. I was ready to throw kayexalate on the hyperkalemic trash heep along with bicarbonate. My co-author, John Asplin calmed me down and had me moderated the section. He explained that despite the lack of data, SPS resins have a long history of use and explained that though I have the option of using dialysis, intensivists often find themselves in binds where dialysis is not available and they need an extra-renal method for potassium clearance.

I can appreciate Asplin’s wisdom now. In the last decade I have used SPS resins innumerable times in patients with and without ESRD, though my data is circumstantial I am believer in the effectiveness of this drug. I hope the latest publicity about the purported ineffectiveness of Kayexalate leads to well done large studies rather than a loss of this effective medicine.

Posted on

The highest urine specific gravity I have ever seen

1.050 is really high. Even the healthiest kidneys can’t concentrate urine past a specific gravity of 1.030. To get this high the urine must contain another substance.

In this patient’s case she had just undergone a heart catheterization. IV contrast is rapidly cleared by the kidney and increased the density of the sample. Proteinuria and glucosuria are other conditions which can cause an abnormally high urine specific gravity.

Ref