Comment on the latest MDRD article and the state of clinical nephro research

Last Thursday in journal club we reviewed the latest data on protein restriction and progression of CKD.

The best summery of the results are provided at the end of the paper:

a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, but had no impact on delaying the progression to kidney failure…

Imagine that the primary results had been different. Imagine for a moment that the MDRD study, rather than being one of the first of the large, NIH-sponsored, negative clinical trials in nephrology, was instead a great success. Imagine that the very-low-protein diets resulted in a delay of dialysis of 20% compared to a low protein diet and that a low-protein diet resulted in a 25% delay in progression compared to a normal-protein diet. Imagine a universe where protein restriction is the ACE inhibitors of our universe.

Now imagine if this most recent analysis came out in that universe. The above quote in this imagined universe would read something like:

a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, despite successfully delaying the progression to kidney failure…

How would we as a nephrology community come to terms with the fact that our primary intervention that we were advocating in a thousand CKD clinics across the land, was actually killing our patients after they start dialysis. Imagine the hand wringing as we start to realize that we were able to delay dialysis from 12 months to 18 months but at the cost of a doubling of their first year mortality from 22% to 40%.

I would be horrified and stop advocating it in my clinic but lots of my patients would adopt the low protein strategy, essentially play the lottery that this radical change in diet would allow them to escape their fate.

We as the nephrology community need to demand better research. This study stands alone (nearly? or completely?) by looking at a pre-dialysis intervention but measuring the outcome in dialysis. This study goes over the wall separating chronic kidney disease research from dialysis research. We need a name for this x-ray vision of looking through the artificial barrier between CKD and dialysis. I propose transitional research.

We need to demand that our CKD research does this. This distinction is less important when looking at CKD 3 where only 1% go on to dialysis; but when looking at CKD4 patients we need to know how that intervention affects dialysis survival. In CKD 4, 18% of patients will end up on dialysis in 5 years. (D. Keith’s data, PDF)

Which of today’s avant garde treatment of CKD results in a doubling of dialysis mortality?

  • Use of active vitamin D to treat secondary hyperparathyroidism
  • Treatment of anemia with ESAs
  • Use of phos binders, calcium based or otherwise
  • Bariatric surgery
  • Aggressive control of blood sugar

None of these “standard” therapies has been examined with an eye on total mortality before and after initiation of dialysis. We need the definitive studies so at some time in the future we don’t have to tell a patient’s family that the pills we have been prescribing may actually have caused the stroke or heart attack or cancer or…

ABG questions and answers

I have been editing our consult month syllabus adding the links for the study materials as we go.

Today we fell off the syllabus. The acid-base lecture on Wednesday revealed a chasm of ignorance. We need to really pound on the basics. So today, instead of doing a Powerpoint style lecture on non-anion gap metabolic acidosis, we sat in a conference room with a couple of calculators and pounded through 23 ABG problems.

Problems
Answers

Acid Base Machine Qs

Acid Base Machine

While we were going through the questions, part of me wanted some tunes. Just saw Slum Dog last weekend.

Who Wants To Be A Millionaire? – TV Themes

MedCalc for the iPhone

I had never heard of MedCalc for the iPhone but MedCalc had been my medical calculator on the Palm Platform since 1999. I noted that this iPhone version had one of the same authors form the Palm Version, Mathias Tschopp.
So one more medical calculator review: MedCalc


For the iPhone version, Mathias has added a second partner, Pascal Pfiffner. This duo has put together a sharp and innovative medical calculator.
The program has created the best system for finding the equations you use. First off the equations are grouped into specialties. Then the program keeps a list of recently used programs and finally it allows you to generate a list of favorites. Mathias and Pascal have created a new system for marking favorites which is not modal. This makes it unconventional for the iPhone but it also makes generating a favorite list less of a chore. Whenever you are browsing through the equations and you see one you want to add to your favorites all you need to do is double tap the equation and it gets marked by a star. Neat. In addition to categories, favorites and recents, MedCalc also allows the user to search for equations.


The other innovation for the calculator is how the user interacts with the formula. The program does not have separate panels for entering data. all of the values can be seen on one page. The number pad is a panel which can be slid out of the way and is slightly transparent. The whole package is very slick. The units for the variables can be switched by selecting the appropriate unit on the right.


The other cool feature is that the program indicates required variables by shading the background pink. Optional data has a white background. MedCalc swithce from the 4 to the 5 or 6 variable formula on the fly depending on what variables the user inputs.

Additionally for the osmolar gap it includes the optional ethanol level. In terms of information supplied with the equation the program always supplies adequate data for the user to interpret the formula. Some of the references are not the ones I would have selected but overall its pretty slick. In terms of weaknesses, there’s no FE Urea. Oh well.

Nephrology calculators for the iPhone

I have three different medical calculators on my iPhone. Two of them I actually use and the third came bundled as part of a different program. I put each calculator through its paces and comment on the differences found in this generally commoditized market.

The three calculators are:

Mediquations was the first medical calculator on the iPhone platform. The author is a third-year medical student, Zack Mahdavi. I have spoken with him and he is a good guy. Since releasing the program in July 2008, he has repeatedly upgraded Mediquations at no additional charge to users. He has focused on adding new calculations to his program and Mediquations has acquired a truly stunning breadth of equations. He claims 201 equations ranging from A-a Oxygen Gradient to Winter for Metabolic Acidosis.

The program has grown large and takes awhile to get past the splash screen and into the functional calculator.

The program then displays a conventional alphabetical list of equations. You can alternatively sort them by categories. Mediquations allows you to bookmark a set of frequently used “Favorites” to easily get past the ton of equations provided.

The MDRD equation is the conventional 4-variable equation and is accurate.

Tapping on a numerical variable sends you to an easy to finger keypad.

Thoughtfully you can switch units on the fly by tapping the i above the units.

For Boolean data you just tap the variable and it gets checked.

Tapping “More Info” gives you the formula and usually a reference and sometimes some background data on how to interpret the calculation. For the MDRD, Mediquations references the Levey paper (PDF) from the Annals which describes the 6-variable, not the 4-variable formula. There is a link which takes you to the PubMed reference in Mediquation’s own web browser.

The execution of “More Info” is spotty. The fractional excretion of sodium gives the formula, a paragraph on how to use and interpret the formula, and a reference to a 1984 American Journal of Medicine article rather than the original Espinel article which introduced the formula or the Shrier paper which validated it. The FeNa info is much better than the FeUrea info which is limited to just the formula without a reference or any help interpreting the calculation. The TTKG falls in the middle with the formula, a short descriptive paragraph which correctly points out that the formula is only valid with a urine Na over 25 and urine osmolality over 300 but gives no guidance on how to interpret the results. Instead of a peer reviewed reference, Mediquations directs people to Wikipedia which, as of 3/2/09, also does not have the correct Halperin reference but does a pretty good job on guiding the reader on how to interpret the calculation.

Overall I give Mediquations three out of four stars. Mahdavi has focused on breadth (200+ formulas!) rather than making the core formulas easier to use and fully documenting those calculations with useful information.

QxMD publishes four different free calculators: Neph (iTunes link), Cards, GI, and HEME. Each calculator has the same equations but the opening screen just shows the namesake’s equations. To get to the other specialties you have to drill down to them. I like this solution to the avalanche of equations found in Mediquation.

Instead of having a favorites tab the equations you use most frequently are automatically added to the Recent list which allows you to generate the same functionality of a favorites list without the work. Nice.

The best feature of NephCalc is a feature called Question Flow. When you turn this on each variable you need to enter is prompted automatically. This significantly speeds data input. For example the data entry flow for Mediquations and the MDRD GFR is:

  1. Tap age
  2. Enter age
  3. Save age
  4. Tap cr
  5. Enter cr
  6. Save cr
  7. Tap African American
  8. Tap Female

For Nephro Calc it is:

  1. Enter age
  2. Save
  3. Enter Cr
  4. Save
  5. Enter African American
  6. Enter Female

It saves two steps and feels a lot more streamlined. Nice innovation.

The Info button leads to a page with interpretive information and a reference. QxMD choose the 2002 K/DOQI guidelines for CKD staging which is probably a great reference, since the 4-variable formula was never published in a peer reviewed journal. The K/DOQI guideline does a nice job of describing the MDRD formula.

The FeUrea information page gives good data on interpreting this calculation and references the KI article (PDF) which put FeUrea on the map rather than the Kaplan and Kohn article where the calculation was first published. I think that is appropriate. (Though it makes me a little sad to see Orly Kohn forgotten for what it is one of the coolest new things in clinical nephrology. Orly was one of my mentor’s at U of C where she runs the PD clinic and is one of the attendings that enriched my fellowship. I remember doing the KI article in journal club and she was in the room and was completely modest about us critiquing her formula.)

With the TTKG QxMD again shines with a good description of how to interpret the calculation, the equation and the correct Halperin reference but the link which promises the abstract doesn’t work.

Like Mediquations however, not every equation has informative “Info.” The osmolar gap simply states “No additional information is available for this topic.”

Overall, I think that Nephro Calc is the best clinical calculator for nephrology and its free. It is not perfect but its close enough to perfect, to be the calculator I recommend to students and fellows rotating with me.

MedMath is bundled as part of Epocrates (iTunes Link). One of the key differences with MedMath is that instead of going to individual pages for each variable all the variables are on one screen. This limits the screen space for a number pad and MedMath uses a non-standard keypad which is significantly smaller than the ones in Mediquation and Nephro Calc. I found it more difficult to tap in the correct numbers with my fingers. I wonder if this is cruft from MedMath being originally written for the PalmOS and stylus-based touch screens.

The MDRD equation pictured is the less often used 6-variable formula. Which means that unless you have the albumin and BUN you can’t calculate the GFR.

The calculated osmolality does not allow one to enter the alcohol level, an omission also found in NephCalc. Only Mediquations allows you to correct the calculated osmolality for ethanol.

For me, the MDRD equation is one of the killer features of a medical calculator so MedMath with its 6-variable silliness totally fails and is a non-starter.

On to the consult service.

My favorite month and the month I dread.
The most stimulating and just the most.

I have two medical students and one fellow. Which is a particularly difficult combination to teach. You have students at the beginning their education and a fellow almost done with her formal training.

My fellow has already told me that she wants to focus on fluids and electrolytes which suits my interests perfectly. It also dovetails nicely with what medical students typically want to get out of a fourth year nephro rotation (especially after rank lists have been submitted).

My plan for the syllabus is:

  • Mon: Ca, Phos, metabolic bone disease (PDF or Zip file for Pages), more acid-base problems
  • Tues: Collectively use mind maps to describe renal physiology Continue to teach ABGs: Anion gap metabolic acidosis with gap-gap (delta gap) and osmolar gap (PDF or Zip file for Pages)
  • Wed: Mind the gap…osmotic gap, anion gap, stool osmolar gap, urinary anion gap Busy clinic, no time for any teaching
  • Thurs: presentation of outlines/abstract of end-of-the-month presentation, non-anion gap metabolic acidosis PowerPoint presentation.
  • Fri: Vacation (for me not the students)
  • Mon: Alcohol and its protean effects on electrolytes Did this March 6th
  • Tues: first student/fellow presentation
  • Wed-Fri: NKF Spring Clinical Meeting
  • Mon: second student/fellow presentation
  • Tues: third student/fellow presentation

It’s an ambitious plan. We’ll see how it goes.

Dialysis report card

One of my 81 year old patients just recently started on dialysis. I took care of her CKD for about 3 years before she needed to start dialysis. Today, we had a care meeting and she told me that she was doing great on dialysis and her labs verified this.

Her pastor reads all the good report cards that the kids in her church bring to him. So she brought in her dialysis report card and her pastor read it on Sunday.

Fluid and Electrolyte lecture at Providence from Friday

Third in the series of interesting fluid and electrolyte cases.

I would add a slide on where I was going in potassium before the anorexia section.

SlideSpace botches the torn paper frames I used through out the lecture so if you have Keynote, download and look at the native file.

Here is a link to the Keynote file.