Hyperkalemia as an indication for dialysis

A few weeks ago we admitted a patient who has been approaching ESRD for a number of years. Most of her medical care had been provided in the hospital as she bounced from admission to admission. Though we tried to get her into our CKD clinic she always failed to show up. You can track the progression of her CKD from hospitalization to hospitalization with a gradually increasing baseline creatinine.

On this most recent admission, she came in with the triple 8s:

  • Hemoglobin 8.8
  • Creatinine 8.1
  • Potassium 8.6

Here is her initial EKG with that potassium:

The most remarkable part of the EKG was the profound bradycardia, heart rate of 30. Also she has beautifully peaked T waves. I’m surprised by the lack of a prolonged QRS. She had a great response to medical management with her K falling to the 5s. The repeat EKG was rather unremarkable.
The patient received dialysis on the day of admission and the following day I set her up for chronic dialysis. Whenever a patient progresses to chronic dialysis from CKD I always try to remind myself of how rare this event is. As nephrologists it is too common and seeing that unfortunate outcome alters our perception so that we may overestimate its frequency. End-stage renal disease is an exceptional, not a routine outcome of CKD. The vast majority of patients with CKD ultimatly expire of something other than renal failure. Let’s review three important studies to emphasize this:
Keith et al looked at the five-year outcome of 28,000 patients with chronic kidney disease. He divided them by CKD stage and found that of the 11,278 patients with CKD stage 3, only 1.1% of then received dialysis and 0.2% received a transplant. A quarter of them died (24.3%). The authors summarized the results:

The likelihood of renal replacement therapy, either transplant or dialysis, was near zero (≤1.3%) for patients in all stages except stage 4, where 2.3% ± 1.1% of patients received a transplant and 17.6% ± 2.7% had dialysis initiated.

Eriksen et al found similar results in a 10-year study, with a 4% risk of renal failure for patients with CKD stage three compared to a 51% risk of death.
And lastly, O’Hare, et al’s VA study that looked explicitly at renal failure and the competing outcome of death. They asked, “At what age and GFR is renal failure more likely than death?”. Obviously, at a younger age, when death is a more remote possibility, a higher GFR will have the time to deteriorate to the point of requiring renal replacement therapy. The results showed surprisingly low GFRs:
To read the graph, find your patients age and then line it up with their GFR. If the intersection is in the black, they are more likely to die, if it is in the grey then hello Mr. Fresenius, nice to meet you Ms. Tacrolimus. Note, that in a 75 year old with a GFRas low as 16 mL/min, death is still more likely than ESRD.
So, the next time you see a patient initiating dialysis after a long run of chronic kidney disease don’t be frustrated by the fact that they didn’t do enough to prevent this, be amazed that they survived to this outcome. 

iGot an iPad

I got a 3g model on Friday and I’m still trying to figure out what I’m going to use it for. How/if am I going to incorporate it into teaching.

Today we had a patient with rhabdomyolysis. The UpToDate cardClinical features and prevention of heme pigment-induced acute tubular necrosis, has this to say about bicarbonate and mannitol:

In a large series of 382 patients with serum CK concentration >5000 U/L, 154 (40 percent) were treated with bicarbonate and mannitol [33]. There was no statistically significant difference in the incidence of renal failure (creatinine >2.0 mg/dL [177 micromol/L]; 22 versus 18 percent), dialysis (7 versus 6 percent), or death (15 versus 18 percent) in patients who were or were not treated with bicarbonate and mannitol. However, there was a trend toward improved outcomes in patients with extremely high CK levels (>30,000 U/L) treated with bicarbonate and mannitol. 

Reference 33 is the primary reference for one of my first blog posts. We started talking about this study on rounds, but the crap machines in the ICU didn’t have Flash or PDF support. I ended up downloading the PDF on my iPhone and four of us passed it around to look at some of the figures. The iPad doesn’t have flash but it does a beautiful job rendering PDFs. I have the article in Papers which does an awesome job at holding and organizing my entire medical library.

Basic review of Papers

Papers is iTunes for scientific Papers. It is the modern equivalent to the file cabinet you always wanted for all the important scientific articles that fall into your grubby little hands. My computer is littered with literally hundreds of scientific articles. What you want to do is throw them all into Papers.

To understand the power of Papers, let’s look at the workflow for getting a PDF into Papers and onto the iPad. After downloading reference 33, drag it into Papers. It initially looks like this:

Then you click on Match and quickly find the article’s reference in PubMed or Google Scholar or another database. To do this I copied the author’s name and entered the year of publication.

After you double click the correct reference all of the meta-data quickly populates the appropriate fields so the you have all the data you need.
Papers even renames the original file, so your reference article folder is organized with logically named files.
To sync your library between your Mac and iPad, just run Papers on both devices simultaneously and it will synchronize your entire Library or specified subset (actually, it is limited to 1,000 articles). Syncing occurs over wifi.

On the iPad, when you launch Papers, you are in the Library.

Search on bicarbonate and you find a couple of articles on the use of bicarbonate to prevent contrast nephropathy, one on its use to treat severe metabolic acidosis, and one on its use to prevent the renal complications rhabdomyolysis…bingo!

Once you have the article you can read it in landscape with some of the meta data revealed or portrait for a more paper-like experience
Papers allows you to annotate, bookmark and share the article
 

Papers also works on the iPhone but after using it I thought it was a bit of a gimmick, I didn’t really want my PDF library on a 3.5 inch screen. The iPad makes a perfect partner for the desktop app. I’m very excited about this.

Papers for MacOS is $42.00, the iPhone/iPad application is $14.99.

Turning PDFs into ePubs

Here is a site which tells you how to convert HTML files into ePubs so they can be used in Stanza or (presumably) iBooks so they can be used on an iPad.

Here is a site that purports to convert PDFs into ePubs but it didn’t work with the one I tried.

Anyone with any experience doing this?

Hypertension Core Curriculum

The Michigan National Kidney Foundation teamed up with the Michigan Department of Community Health to create a primer on hypertension for doctors, nurses and midlevel providers. The book just was finalized. The book is not copyrighted so I am able to upload it for people to use as they see fit.

I authored the subsection on lifestyle changes and blood pressure control.

Enjoy

Hypertension Core Curriculum

The problem with the K/DOQI stages

In 2002 at the Spring Clinical Meeting of the National Kidney Foundation, K/DOQI released the Clinical Practice Guidelines for Chronic Kidney Disease Evaluation, Classification and Stratification.

These guidelines have become the dogma of CKD and all of my residents can accurately determine the CKD stage of their patients. The classifications have allowed epidemiologists to measure the burden of CKD. The crux of the guideline is that the severity of kidney disease is solely determined by the GFR.  This is helpful in determining where the patient has been but it is not good at determining where patients are headed.

In some ways, it is a negative prognostic tool, people with worse stages of CKD actually have better outcomes and vice versa.

To understand how this works one needs to understand how we calculate the GFR. The accepted equation was created by Levey et al using the MDRD data base. Levey AS, Greene T, Kusek JW, Beck GJ: A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol 11:A0828, 2000 (abstract)

GFR=186 x sCr -1.154 x Age -0.203 x (0.742 if female) x (1.212 African-American)

African Americans, for the same creatinine, are given a 21% increase in their GFR and women lose 26%. If GFR provided prognostic information one would think that African Americans were protected from chronic kidney disease and women were at higher risk. Yet that is not the case. African Americans have the highest rates of ESRD, 998 per million compared to 273 for white Americans: (USRDS 2009 Annual Data Reports, NIH, NIDDK, Bethesda, MD, 2009.)

The lifetime risk of ESRD is 1 in 50 for woman and 1 in 40 for men (Kiberd BA, Clase CM. JASN 13: 1635-44, 2002).

The negative exponent on the age variable means that as one ages their GFR falls. The problem is that the risk for ESRD appears to fall, likely because of the competing endpoint, death. This was best shown in a 10 year study by Erikson and Ingebretsen. They showed that as patients aged they were more and more likely to die and less likely to develop ESRD.
I do not doubt that the MDRD eGFR is a good measure of renal function I am frustrated by the way it is used to frame management decisions.
Its like the nephrologists in the K/DOQI work group looked at the framework established in oncology and adopted a staging system but did not consider the importance of the grading system. Not all CKD stage threes are alike, some patients have more aggressive disease than others and this needs to be addressed in our clinical practice guidelines.                                                            

Best urine quotation

“What is man, when you come to think upon him, but a minutely set, ingenious machine for turning with infininite artfulness, the red wine of Shiraz into urine?”

Isak Dineson, Danish author (1885-1962)

I first heard this quotation from my mentor Adrian Katz. Only Adrian would compare the wine you were currently drinking to urine. 

How I used my newly acquired PubMed skills

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.

After I finished the lecture I spent some minutes playing with my new skills on PubMed and found this article: N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients that completely goes against one of the figures and points of my newly scribed chapter:

[The inability of acetylcysteine to prevent dialysis or mortality] maybe because acetylcysteine alters creatinine handling in the proximal tubule. Acetylcysteine, actually accelerates the excretion of creatinine resulting in decreased serum creatinine.

After Tepel published his original work on acetylcysteine in 2000 everyone went a little crazy drinking the Mucomyst cool-aid. Here was a cheap, safe and already approved, remedy to the pervasive problem of contrast nephropathy. Everyone was so drunk with the excitement that they didn’t note that the 85% reduction in contrast nephropathy was not associated with a reduction in the need for acute dialysis or a reduction in patient morbidity and mortality.

In 2004, Hoffmann Et al. published the above quoted article which showed a modest but significant reduction in serum creatinine following ingestion of acetylcysteine. This seemed to me to be the best explanation for why a therapy could prevent an increase in creatinine but not prevent dialysis. (Data on the lack of prevention of dialysis from Miner et al. Am Heart J 2004.)

Apparently the patron saint of contrast nephropathy, Richard Solomon, recently reevaluated this theory and found it lacking. He took 30 patients with GFR < 60 mL/min and given 1,200 mg of acetylcysteine every 12 hours for four doses. Creatinine and cystatin C were measured at baseline, 4 and 48 hours after the last dose of acetylcysteine. They found:

Serum creatinine and cystatin C levels did not change significantly at either 4 h or 48 h following the last dose of NAC compared with the baseline values (Table 2; Figures 1 and 2). However, a small but statistically significant reduction in the ratio of serum creatinine to cystatin C was observed at 4 h but not 48 h.

click to enlarge
Solomon postulates that in patients with chronic kidney disease (a population that better represents the people who actually are given contrast nephropathy prophylaxis) the proximal tubule secretion of creatinine may already be maximized so that it cannot be further upregulated by acetylcysteine.
The end result is that changes in creatinine found during acetylcysteine administration likely represent changes in GFR and are not merely artifactual.

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.

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

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.