Remember Nate Hellman

Nate started the most important innovation in nephrology education since NephSAP, the Renal Fellow Network. Nate died, tragically, a year ago this past Sunday. We all stand on the shoulders of giants and Nate passed long before his work was done. In addition to thinking of Nate, we should also thank Matt Sparks and Conall O’ Seaghdha for picking up the pieces and transforming RFN from what was largely a one man show into the institution it has become.

Creatinine, BUN and GFR: part one

Question: What is the most basic concept in clinical nephrology?

Answer: As renal function falls, the creatinine and BUN rise.

For the purpose of this post the renal function is synonymous with glomerular filtration rate.

Think about every lab measurment in clinical medicine and think about how the normal range changes as the GFR falls from 100 mL/min to 10 mL/min, a 90% reduction of renal function.

  • How much does sodium change? 
    • Not at all.
  • How much does potassium change? 
    • In the absence of ACEi or other drugs which alter normal renal handling or an extreme change in diet, it doesn’t change at all.
  • Phosphorous? 
    • Maybe a 25% bump from the low 4s to the mid 5s.
  • White blood cell count? 
    • Not at all.
  • Albumin? 
    • Not at all.
  • Lipase? 
    • Not at all.
  • SGPT? 
    • Not at all.
In the broad world of clinically relevant biochemical tests, essentially none are readily affected by changes in glomerular filtration rate. BUN and creatinine (and cystatin C) stand alone in their exquisite sensitivity to changes in GFR. Of course this is not a weird coincidence, those labs are clincially relevent precisely due to their sensitivity to changes in GFR. But why is it, that as GFR falls, the creatinine rises?
Imagine a 70 kg male. Men, on average, generate 20 mg of creatinine per Kg body weight, so our patient will generate 1400 mg of creatinine and, if the renal function is stable, all of that creatinine is excreted by the kidneys every day. It makes no difference if the GFR is 10 or the GFR is 100, all of the creatinine generated is excreted.

None of it lingers.

None of it accumulates in some creatinine depot in the subcutaneous fat or lateral horn of the cerebral ventricles.

This has to be true because if some of creatinine hung around and accumulated, the serum creatinine would rise. By definition, stable renal function means the creatinine doesn’t rise. So our 70 kg man generates 1,400 mg of creatinine and excretes 1,400 mg of creatinine.

Once you know the amount of a substance excreted we cane solve for the plasma concentration using the standard clearance formula.
Using the 1,400 mg of creatinine, assuming a modest urine output of 1 liter and assuming a GFR of 100 the equation looks like this:
We can rearrange the equation to solve for the plasma creatinine:
and if you do the calculation you get a creatinine of 0.97 mg/dL. The neat part of the equation is that it is totally independent of the urine volume. If the patient excretes the 1400 mg of creatinine in 2 liters rather than 1 as we claculated above, the urine creatinine concentration falls by half (same amount of total creatine dissolved in twice as much urine), the urine volume doubles and the serum creatinine remains the same.
On the other end of the renal function spectrum, the poor patient with a GFR of 10, looks like this:
This gives him a serum creatinine of 9.7 mg/dL. The creatinine went from 0.97 to 9.7 with a change in GFR from 100 to 10. Imagine if any other electrolyte had a ten-fold change associated with a drop in the GFR? Raise your hand if you have seen a potassium of 40.

President Bush is 5’11”

You can use this spreadsheet below to predict the serum creatinine based on different GFRs, urine volumes and creatinine production. Try different urine volumes and see how that doesn’t affect the serum creatinine (the reason is that the numerator in the clearance formula is simply solving for the mass of creatinine excreted. Concentration of X multiplied by the volume gives amount of X dissolved in the solution.) . Use the spreadsheet to discover what Shaquile O’Neal’s serum creatinine is. Assume 20 mg/kg body weight, a weight of 147 kg, and a GFR of 120.

If you want to edit and use the equation image files download this Word file. Double click the equations to launch the equation editor.

Great site with lots of resources on hypertension

The Michigan Department of Community Health has put together a great resource, High Blood Pressure University, which links to resources all about hypertension. The links are divided into three campuses:

  1. Professionals for medical providers
  2. Community for church’s and community organizations
  3. Patient for people with high blood pressure
Take a look at the Vital Signs fact sheet from the professional campus. This is from the CDC and summarizes some of the broad epidemiology of lipids and hypertension.

Hanging in the TWiT Cottage with Leo Laporte

My wife and some friends took a trip to Sonoma California to taste some wine and recuperate midway through the winter. Of course Sonoma is only 10 miles from Petaluma, so I needed to make my pilgrimage to the TWiT cottage.

I got to sit in the pole position during The Tech Guy radio show.

Leo crooning for satellite radio.

The left monitor is what was going out live on the internet. The monitor on the right was a preview. 

Leo’s Emmy, strategically placed in from of the needlepoint advising him to remain humble. Awesome.

This post from Dr RW is great

Must read post about a recent Lancet paper comparing outcomes for patient treated for health care associated pneumonia (HCAP) and looked at outcomes based on adhering or non-adhering to the ATS and IDSA guidelines.

Spoiler alert: patients treated off guidelines did better.

ASN Renal Week Day 2: Harrisons, UpToDate and the Renal Fellow Network

I grabbed dinner with Matt Sparks, one of the driving forces behind the Renal Fellow Network. It was a great dinner and, for me, was the first time I had a chance to talk shop with another blogger. Very fun. One of the things we discussed was the role of blogs in fellow education (this idea was matured a little with a discussion with Conal O’ Seaghdha, the other half of inspiration that drives RFN.

I believe that the primary educational material for medical education has gone through three phases. In the beginning was the medical text book. This was exemplified by Harrisons which rose to ascendancy not by being the first text book but by being the most innovative. Harrison unique innovation was arranging the sections by patient complaint rather than by disease. Here it is described in a fascinating history of the Harrison family of doctors:

PRINCIPLES OF INTERNAL MEDICINE would offer medical students a new way of approaching patients. The Cecil Textbook of Medicine, which had previously monopolized the American medical textbook market, took a less helpful approach. Its author, Russell Cecil, M.D., of Cornell Medical School in New York, had organized the textbook exclusively by disease, offering the definition, cause, symptoms and signs, methods of diagnosis, treatment, and prognosis for each one. This meant, of course, that a student must identify the patient’s disease before the book would offer help. Principles of Internal Medicine, on the other hand, began with the patient. Tinsley [Harrison] devoted the first third of his textbook to symptoms and signs experienced by sick people, which included shortness of breath, swelling of the feet, and so on-leading from there to understanding the disease. The text mirrored the ideal practice of a physician. The first edition of his book, published in 1950, proved an instant and major success.

The second phase was UpToDate. Burton “Bud” Rose (how can Wikipedia not have an entry on Dr. Rose?) crushed the primary medical references by creating a comprehensive, readable and searchable reference. He also cajoled his authors to make specific treatment recommendations so Up-To-Date is the only medical reference that actually teaches you to take care of patients. One of my friends used to complain that when she would invest the hours and tears needed to read a chapter of Harrison’s she would finish with tremendous knowledge and the ability to shine on atending rounds but have no idea how to treat her patient. UpToDate is not like that and has probably saved more lives than ACLS. I routinely ask prospective fellows about their reference of choice and for three years running every single one of them has answered “UpToDate.”

As good as UpToDate is it has some weaknesses. The EBM zealots take it to task for relying on expert opinion but I really don’t have too much concern about that (my previous post on that took them to task for saying they are EBM when they are really an expert opinion source. That’s why the list of author/editors is so important and impressive. They should be proud of what they are rather than claim to be EBM) .

What concerns me is UpToDate’s inability to escape its CD-ROM DNA. I have been a subscriber to UpToDate since I was a resident and Burton Rose was still answering the phone to deal with bad CDs and pimping the still incomplete product in the hallways of Renal Week. The ascendancy of the Internet has allowed UpToDate to get out of the CD shipping business but they still refuse to link out even when it makes overwhelming sense. All of their articles are fully referenced, but not with links to the primary data or the pubmed reference but to an internal database record of the reference.

I get that isn’t too hard to copy the PMID and drop it into google and that will pull the article, but why doesn’t UpToDate just link-out?
This goes for other area where a link out makes sense. Here is a segment of UpToDates card on “Overview of the management of CKD in Adults”
Wouldn’t you expect, reference 8 to take you to the K/DOQI guidelines. They are free and available on the internet. UpToDate instead links to their internal reference of the AJKD supplement with the original publication of the K/DOQI guidelines, which are behind an Elsevier pay wall.

It feels that the editorial rules for UpToDate were created in the CD-ROM era of the 90’s and haven’t been updated for the internet era.

I beleive that, just as Harrison had an openning in the Internal Medicine textbook space by using patient oriented complaints to organize his text and Rose had an openning by using search and a unique editorial style, the technology of today provides a niche. I want an interactive textbook of medicine with comments, a Facebook “Like” button, a way to connect with other practitioners and share treatment pearls.

The renal fellow network and other knowledge focused medical blogs are early progenitors of this future but some pretty large problems need to be addressed:

  • Organization. Blogs are reverse chronologic order by convention but given the random way that topics get posted, it makes for an unorganized structure. Solutions that are being used now include search and tags. Unfortunately, the tag clouds are so huge that they border on the useless. Search is good but a more structured table of contents and/or index would be great. I am delighted with the addition of the lecture and handout tabs on PBfluids, its a step that allows, at least me, to find things I have posted here before.
  • Expiration of old data. Medicine is always evolving. Today’s truth is tomorrow’s MMR-autism fiasco. These medical blogs need a way to mark expired information as such. A perfect example is the ATN trial by the VA and NIH. Prior to that study I was firmly in the more dialysis for acute kidney injury camp. After that was published I marked my acute kidney injury lecture, as being pre-ATN trial. This meant something to me, but my readers likely had no idea what that meant. How many other educational resources were obsoleted by that medical about-face?
Nephrology on demand looks like they are another group making good progress in this mission. Look out UpToDate, Web 2.0 has you in our sights.

– Posted using BlogPress from my iPad

Pregnant Gitelman Patient follow-up

Last week I posted on my pregnant patient who has Gitelman’s Syndrome. I am managing her with amiloride and a mixture of oral potassium and a mixture of oral and IV magnesium.

I received the following letter from a reader who went through a similar experience:

I am not a doctor, but I have Gitelman’s, and 16 years ago, was pregnant and ended up having to go on amiloride at the start of my second trimester, because my potassium and magnesium levels just tanked.   Being part of proving the track record on the viability of amiloride in pregnancy was a scary time, I tell you what.  Your patient’s experiences are similar to mine, though I did not require the magnesium IVs she apparently does during gestation. 

The great news is my son turned out healthy, and without any sign of potassium disorders of any sort, so far as we can tell at nearly 16.  He’s healthy, bright, nearly 6 ft – no indication at this time  that he was harmed in any way by the fetal exposure to amiloride. 

And another point to pass along – after he was born, I had my breast milk checked for traces of amiloride, and it passed whatever screens were applied. Therefore I nursed him for about 9 months, though I supplemented with formula.  It was an acceptable risk for me – since I know the literature does not record any data on nursing while on amiloride, I thought I’d pass along one uncontrolled anecdote for you to ponder. [Note: on further communication the patient clarified that she did not take amiloride during breast feeding

Anyway, please pass this information along to your patient – I am sure it will help her peace of mind to know another successful long term outcome.  It was a scary time for me, and without the widespread use of Internet back in 1995, the only piece of mind I got was by tracking down Dr. Almeida, who wrote the 1989 paper about Gitelman’s in pregnancy.  I spoke to one of his nurses to see if they could give me some info on long term followup on the baby, but the mother had disappeared after giving birth, and they had nothing to report.    

Best of luck to your patient – I know what she’s going through. 

Final note for your patient going forward: Getting my levels back up after the birth was a bit of a challenge, I recall.  But many of the details have been lost to time and the fog of war, I’m afraid – I will just say that the first month post-partum was pretty rough on me.