And the data keeps rolling in…

I am a believer in Richard Johnson’s theory regarding fructose uric acid and hypertension/CKD. So I love it when I see another study adding to the foundation. This from Diabetes Care. The investigators looked at 1500 patients with diabetes and normal renal function and no proteinuria. Over 5 years they tracked who developed CKD (either GFR<60 or proteinuria):

During a 5-year follow-up period, 194 (13.4%) patients developed incident CKD. The cumulative incidence of CKD was significantly greater in patients with hyperuricemia than in those without hyperuricemia (29.5 vs. 11.4%, P < 0.001). In univariate logistic regression analysis, the presence of hyperuricemia roughly doubled the risk of developing CKD.

Write your own text book, save money

I bet this becomes a real trend as school districts become short for cash.

Anoka-Hennepin teachers write their own online textbook, save district $175,000

Instead of mass-produced textbooks, the more than 3,100 sophomores in the state’s largest district are learning from an online curriculum developed by their teachers over the summer with free software distributed over the web.

 For the extravagant tuition charged at medical schools it seems they should throw in the course materials for free. No?

Dynamed versus uptodate

I received the following announcement from our hospital librarian

We are conducting a trial of the online clinical resource Dynamed for the month of November.  We wanted to get some feedback on this product as an alternative to UpToDate, or possibly as an addition to our electronic resources before we negotiate with UpToDate.

So to check it out I did a quick tour of UpToDate and then the same tour on DynaMed. I recently diagnosed a patient with Goodpastures so I looked that up in both databases.
UpToDate
UpToDate has a great autocomplete system for search terms. Not sure if Goodpasture is one or two words? Don’t worry, typing “Good” is good enough.
The number of topics on Goodpastures is remarkable.
I love how the topic outline slides opens on the right when you hover over a topic. When I selected Treatment of anti-GBM antibody (Goodpasture’s) disease I was treated to 3500 words (excluding references, of which there were 32) written by an editor team that puts their name to the review. In this case the authors are all tops in glomerulonephritis:
The article is long, detailed and tells the reader exactly how to treat the patient. What drugs, alternative treatments, how to pheresis including replacement fluid, schedule, dose and duration. It is beautiful in its completeness.
DynaMed
I typed in Good, no autocomplete at all. I searched Good and good pastures is not on the first page of search results. 
I searched Goodp and got nothing.
Searched Goodpastures and…jackpot! They even have the roll-over see the outline trick from UpToDate. Nice
The actual article though, is terrible compared to UpToDate. They have a single entry on Goodpastures which is barebones outline of the condition.

The treatment section contains 159 words, and really gives you no idea how to treat this condition. In fact, about a third of the treatment section is dedicated to combination ACEi and ARB therapy, a window dressing issue in the treatment of this rapidly progressive and potentially fatal disease. I would give this reference a failing grade. You read all 159 words and have no idea what to do. You need to go to a second source.

Their is no author associated with the outline of Goodpastures. Dynamed’s editorial team does not list any nephrologists. The editorial board does have a single nephrologist, which is exactly how many podiatrists they have on the board.

As my colleague, Dr Steigerwalt, said, it should be spelled DinoMed as in Dinosaur.

AJKD launches a blog

Say hello to eAJKD. Kenar Jhaveri of Nephron Power is the editor and he has enlisted much of the nephrology blogosphere, including your humble author to assist him on this endeavor.

Recently some of the all guard of media have started compelling blogs (see the New York Times’ page of blogs for an example). Medical publishing seems to have lagged in this phenomenon.

All of the interesting medical bloggers are independent agents, though The Lancet, JAMA and NEJM have all launched blog initiatives.

I hope that eAJKD aspires to be something special, I’ll do my best to assist it.

It should be a fun adventure.

Crazy numbers: the lowest hemoglobin I have ever seen

When I was a resident I saw a really low hemoglobin. I don’t remember what the number was but I remember the circumstances. I was working the ER at Riley Children’s hospital and EMS pulled up with a infant who was short of breath. The family had been feeding him cows milk instead of formula and as a result he had severe iron deficiency anemia. Great case and after a few transfusions and some parental education, everyone lived happily ever after.

Last week I saw another lowest hemoglobin. Since I wasn’t blogging when I was a resident I don’t know if this hemoglobin is lower than that poor kid but here it is:

Hemoglobin of 3.6 g/dL. The hematocrit is still a double digit number, but still that’s a really low hemoglobin.

This is a dialysis patient who started having some vomiting that looked a little “dark” but didn’t really bother him. A day or so later he developed some dark colored diarrhea. Still didn’t bother him. Then he found himself short of breath, like he missed a treatment and got volume overloaded. This kept getting worse so he finally decided to get in his car and drive to the ER. The admitting hemoglobin was 3.7 followed by a repeat by I’m sure a disbelieving ER doc.

Diagnosis duodenal ulcer and after a half dozen transfusions and a prescription for BID omeprazole he was discharged home to lived happily ever after.

Articles that changed the way I practice: ACCOMPLISH

I was searching PBFluids and could not find any posts about ACCOMPLISH which surprised me. I then went to the Renal Fellow Network and found a similar lack of commentary. Dito for Nephron Power, and Nephrology on Demand. Even The Kidney Doctor with 100+ posts (and in the process putting the rest of the nephrology blogosphere to shame) in the last 2 months comes up empty handed.

Now some of this may be due to faulty blog search and some of this may be due to the fact that the study is approaching 3 years of age, but regardless ACCOMPLISH is important enough that it should get higher profile coverage.

The study was published in the NEJM in 2008

The acronym is an obviously:

  • Avoiding 
  • Cardiovascular events through 
  • COmbination therapy in 
  • Patient 
  • LIving with 
  • Systolic 
  • Hypertension

From the title, if not the acronym, the point of the study should be clear: The study pits benazepril and amlodipine (Lotrel) against benazepril and hydrochlorothiazide (Lotensin).

The politics of this fight are interesting as this study tries to right one of the possible mis-steps in the wake of ALLHAT. ACCOMPLISH used the thiazide diuretic that is actually most often used in the U.S. and the only thiazide that is used in combination pills, hydrochlorothiazide (yes I know I’m ignoring Tenoretic, atenolol and chlorthalidone, but every other combination pill uses hydrochlorothiazide). ALLHAT used chlorthalidone as its diuretic and when this largest-ever hypertension study concluded that there was no difference among chlorthalidone, amlodipine and lisinopril on fatal coronary heart disease and non-fatal heart attacks, thiazides became institutionalized as the primary agent to treat hypertension.

Figure depicting the primary outcome from ALLHAT
The money shot from JNC7 (pdf) institutionalizing thiazide-type diuretics

The problem stems from the fact that hydrochlorothiazide and chlorthalidone are unique molecules with significant biologic and pharmacokinetic differences.

This year Dorsch et al re-analyzed data from the MRFIT trial. This was a long-term primary prevention trial from the 70’s that changed protocols mid-stream and converted patients from HCTZ to chlorthalidone. This allowed Dorsch’s team to look for differential effects of the two diuretics. They found a 21% reduction in cardiovascular events with chlorthalidone:

If you are interested in the reasons behind the differences read John Flack’s editorial associated with Dorsch’s analysis and look at a 2004 review by Carter et al.

So ACCOMPLISH set out to show that the ACEi CCB combination is superior to the ACEi HCT combination. They randomized 11,506 patients to one of these two arms. The dosing titration seems fair:

  1. 20 benazepril and either 5 of amlodipine or 12.5 of dydrochlorothiazide
  2. if BP is not < 140/90 (130/80 in CKD and DM) increase to 40 mg of benazepril
  3. if BP is not < 140/90 (130/80 in CKD and DM)  increase to 10 of amlodipine or 25 of hydrochlorothiazide
  4. if BP is not < 140/90 (130/80 in CKD and DM)  add additional agents as needed
The cohort was rather sick with previously diagnosed hypertension and an additional history of at least one of the following:
  • Coronary events
  • Impaired renal function
  • Peripheral artery disease
  • LVH
  • Diabetes.
The end point was time to first cardiovascular event, or death from cardiovascular disease.
The study was well run but the blood pressures were not perfectly equal between groups with a small but statistically signifigant difference in the blood pressures between the two groups:
  • 131.6/73.3 in the Benazepril-Amlodipine group
  • 132.5/74.4 in the Benazepril-Hydrochlorothiazide group
  • A difference of 0.9/1.1 in favor of the Benazepril-Amlodipine group
The study was terminated early because the data and safety monitoring committee observed a difference between the two groups that exceeded the pre-specified stopping rule. They found a 20% risk reduction in only 30 months. This represented an absolute risk reduction of 2.2% which translates into a Number Needed to Treat of only 45.
Entering EBM free zone:

To my eyes, ACCOMPLISH better represents the patients I see than ALLHAT. All of the patients that come to my CKD clinic have high blood pressure and almost all also have the additional co-morbidities needed for enrollment. After fully digesting ACCOMPLISH I have made two changes in my practice pattern:

  1. I am starting patients with ACEi + CCB or ARB + CCB. I have been impressed by the effectiveness of Lotrel and Exforge as single pill solutions to a lot of hypertension.
  2. I avoiding hydrochlorothiazide where ever possible. This usually requires re-jiggering a number of medications but a common switch will be to move patients from a list that looks like this:
    1. Lisinopril HCT
    2. Amlodipine

          To a list that looks like this:

    1. ACEi CCB combination pill
    2. Chlorthalidone

This results in significant improvement in blood pressure control.
I have to thank ACCOMPLISH to opening my eyes to this change.

Nephrology blog-together at Kidney Week

Next week is ASN’s Kidney Week in Philadelphia. Some of the kidney bloggers are going to be getting together to clink glasses and talk blogging, kidneys, MedEd and whatever else spills from our lips. We are meeting at McGillin’s Olde Ale House.

When you get there look for the nerdy guys who look like they spend too much time staring at an screen.

Friday, November 11th at 8 pm
McGillin’s Olde Ale House
1310 Drury Street
Philadelphia, PA 19107
215/735-5562
www.mcgillins.com

Hope to see some of you there, and remember when you are tweeting about Kidney Week use the hashtag #kidneywk11

No! No! No! Never! Give a dialysis patient a Fleets Enema!

What is wrong with this picture?

Sevelamer and Fleet Enema. They go together like a honey baked ham and Chanukah. Fleets enemas have an obscene amount of phosphorous and sevelamer (Renvela) is a phosphorous binder. They should never co-mingle on the same MAR. So while some may see a couple of benign medications, I see a Chanukah ham.

A  Fleets enema, or any typical sodium phosphorous enema, is roughly 4 onces or 120 ml. The active ingredient is sodium phosphorous, to the tune of 26g of sodium phosphate per dose, some articles quote a phosphorous concentration of 13,000 mg/dL. Remember, a normal diet has about 1 gram of phosphate and only 700 mg of that is actually is absorbed; so we are talking about a potentially massive overdose.

I love that someone scanned the entire packaging

No patient with kidney disease or on dialysis should get this drug without talking to their doctor. Its written right on the damn package.

I guess, if you are in the hospital and the doctor orders it, that is essentially the same thing as asking your doctor. Too bad that over and over again doctors express their ignorance about dangerous this seemingly innocuous medication can be by ordering it in patients with kidney disease.

A rogues gallery of bad outcomes from the lowly Fleets Enema

The sodium phosphorous enema can be lethal to a patient with kidney failure.

Here is a case report regarding a patient who developed hypocalcemic tetany and coma following a single enema

My favorite quote in the case report is the hyperphosphatemia review of systems:

…the family denied that other drugs or unusual food such as star fruit was given by them- selves.

They gave the patient a couple of amps of calcium gluconate and then dialyzed him on hospital day 6, 7 and 8.

The situation is even more harrowing if you give the enema orally. This results in massive sodium and phosphorous absorption. In this case report the team gave it to the patient…twice:

They ran in to trouble while treating a toxic theophylline level. They gave activated charcoal to bind the theophylline. Subsequently, the patient developed an illeus and was given 120 mL of a sodium-phosphorous enema down the NG tube. The next day he received 4 liters of polyethylene glycol via the NG and finally another 120 ml sodium phosphorous enema enterally.

Then he arrested.

They resuscitated him. Here are his post-code labs:

  • Na 177
  • K 2.8
  • CO2 18
  • Cr 3.4
  • phosphate 59.6
  • calcium 5.2
  • Ca x Phos product: TFTC*
  • pH 7.12/37/40

* Too frightening to calculate

After resuscitation the patient was too hemodynamically unstable for dialysis and died during a subsequent arrest.

Look at that phosphorous! A phosphorous over fifty is like a traffic accident, can’t tear your eyes away.
Here’s a simple rule:

If the medicine is supposed to go in the butt, don’t feed it to your patient.

As high as the phosphorous is however, the symptoms are due to the low calcium. The high phosphorous complexes with the calcium driving the ionized calcium down.

JASN published a tight review in 1996. They discuss an unfortunate case where a gentleman was prescribed two enemas for a flexible sigmoidoscopy prep. The patient however, mistakenly ingested them orally rather than, you know, using them the right way. 191 mmol of sodium and 208 mmol of phosphorous down the hatch. The patient presented to the ER complaining of foot and hand pain along with diarrhea and difficulty swallowing and speaking. Data on presentation:

  • QTc 0.6 sec (prolonged)
  • ionized calcium 0.34 mmol/L
  • total calcium 4.5 mg/dL
  • Na 154 mmol/L
  • phosphate 44.8 mg/dl
  • anion gap 39

The patient was managed with insulin and dextrose, aluminum hydroxide and IV calcium gluconate along with IV fluids. Dialysis was delayed for 4 hours due to difficulty gaining IV access. He was dialyzed against a high (3.5 mg/dl) calcium bath

One of the points I tried to highlight in the graph is the rapid drop in the phosphorous prior to the dialysis. The conservative therapy of IV fluids, insulin, and aluminum hydroxide look highly effective. Also note how effective dialysis is at raising the calcium.

The authors make an excellent point regarding the acidosis. The patient had an initial pH of 7.28 and an anion gap of 39. The anion gap is from the high phosphorous. The authors point out that treating the acidosis with alkali will further drop the ionized calcium and is contraindicated until the calcium is corrected.

The discussion of the paper is delicious and addresses a situation I have found myself debating with fellows. The question is what to do when the phosphorous is really high and the patient has hypocalcemic symptoms. Does the administration of calcium lead to metastatic calcification to the detriment of the patient? The authors feel that calcium should be given to treat the symptoms of hypocalcemia and delay full treatment of hypocalcemia until the phosphorous is restored to normal levels.

In terms of personal experience, the MAR from the top of the post comes from a dialysis patient who did receive a Fleets enema while in the hospital. His phosphorous went from 3.5 to 11.7, overnight. He remained asymptomatic but the whole experience terrified me.

No. No. No Never. Give a fleets enema to a dialysis patient.