Happy birthday PBFluids

PBfluids.com turned 2 years old on May 30th.

283 posts with another 24 drafts that have not yet seen the light of day.

283 posts in 730 days is one post every two and a half days. Not bad.

Abacavir and methanol poisoning

About a month ago, Nephron Power wrote about a great electrolyte case in AJKD. The case regarded a patient who drank a liter of methanol but was asymptomatic. The reason the patient was apparently resistant to a toxic methanol slug of methanol (The quantity of methanol that produces toxicity ranges from 15 to 500 ml of a 40% solution to 60 to 600 ml of pure methanol) was protective powers of abacavir. Abacavir is a nucleoside reverse transcriptase inhibitor and apparently, is a potant inhibitor of alcohol dehydrogenase, the critical enzyme which converts methanol into formaldehyde. Formaldehyde is then converted into the lethal formic acid by formaldehyde dehydrogenase.

After reading this I started to wonder if abacavir was such an effective inhibitor of alcohol dehydrogenase what happens when patients get exposed to say a more common substrate of alcohol dehydrogenase such as whiskey. Shouldn't we hear about people on abacavir going on alcohol benders after a single shot of ethanol?

A couple of cracks at PubMed and I sure didn't find much. Barber, Marrett et al. looked for two types of alcohol reactions from abacavir, either a disulfaram-like reaction or reduced alcohol tolerance. The authors found three cases of in 173 patients starting abacavir. They found one disulfarem reaction (nausea, tachycardia, flushing with a single shock of vodka) and two cases of decreased alcohol tolerance

After three glasses of wine he felt as though he had a bottle and a half, with memory loss.

The only other paper I could find was by McDowell, Chittick, et al. who looked at increased abacavir levels with alcohol intake. The reverse of what I was looking for, but at least it was related. They gave a single dose of abacavir and 0.7 g/kg of ethyl alcohol to 25 HIV positive men. They found a 26% increase in the half life of abacavir with alcohol but...

This study did not demonstrate any alteration in the pharmacokinetic parameters of ethanol by abacavir coadministration; blood ethanol median profiles following ethanol administration in the presence and absence of abacavir were essentially superimposable. There was no evidence that co-administration of abacavir interferes with ethanol metabolism. There were no disulfiram-type reactions in any subject who received coadministration of abacavir and ethanol.

This study tested the effects of a single dose of abacavir, chronic dosing may result in a different effect on alcohol dehydrogenase.

Interesting case nonetheless.

Flattering review of the Fluid and Electrolyte Companion

Not everyday that you get a new review of a ten year old book. Thanks Beaver Medic.

My feelings about kidney transplant

Organ transplants are best left to professionals

- Bart Simpson

via Rob Haung (@DrRobH)

David Spiegel on the treatment of dialysis patients

There are only two outcomes that are important: quantity of life and quality of life. We don't know how to measure quality of life and haven't shown an ability to change the former.

- Posted using BlogPress from my iPad

The dangers of high dose vitamin D

Back in November I posted on a patient who had a dramatic improvement in her PTH following correction of her vitamin D deficiency. One of the comments was:

Anonymous said...
Why wait one entire year to correct the Deficiency. I would have treated with 100,000 units po qd for 5-10 days.

I responded...
Regarding the time to treat the patient. This patient had almost no appreciable renal disease outside of the SHPTH. I was not going to schedule frequent visits to monitor therapy I just put them on a safe and familiar vitamin D dose and followed up every six months. I don't think I harmed the patient with slow therapy. The one time I had a patient on 50,000 units daily (resident error) they were readmitted within 2 weeks with hypercalcemia.

What I was really thinking was I never considered a more aggressive replacement regimen. This weeks JAMA provides some insight in the potential dangers of rapid and high dose vitamin D replacement. It is a randomized, placebo-controlled study looking at whether giving half a million units of oral cholecalciferol once a year can reduce the number of falls and fractures. Surprising, at least to me, was the higher risk of falls in the experimental group.

The investigators did a post-hoc analysis on the timing of the falls and found they were more likely to occur right after the vitamin D and the risk attenuated as more time passed after the dose. Thus implicating the drug itself as the cause.

The accompanying editorial is quite good and provides references for additional studies that also point to higher fall risk with high doses of vitamin D.

The sugar in soda

From a pretty good article in Fast Company of all places:

But come on, are sodas really so bad? Even coffee drinkers like to use a little sugar. Should we demonize coffee, too? Well, as a thought experiment, imagine that you're in the office kitchen as a colleague adds some sugar to his coffee. As you watch, he adds a teaspoon. And then another. And another. And another. And another. And another. And another.And another. And another. And another. And another. And another. And another. And another. And another. And another. (Dude, want some coffee with your sugar?)

 

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 card, Clinical 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.