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My philosophy of consult nephrology

If, on every consult for acute kidney injury, you limited your differential to pre-renal azotemia, obstruction and run-of-the-mill ischemic ATN you would be capable of reaching the right diagnosis 95% of the time. Common causes of renal failure are common. All the time we spend learning and teaching about glomerulonephritis, interstitial nephritis, vasculitis and the other zebras of acute renal failure is usually time wasted. However, your job as a consult nephrologist is to hunt down and flush these zebras. I strive to try and fit every clinical scenario into one of these alternative rare diagnosis. Because if you are not actively hunting a zebra, you will never find one.

When you see community acquired pneumonia and the ICU intern mentions that there was a lot of blood during the intubation your mind needs to starting thinking about pulmonary-renal syndromes. Ask the family about a history of sinusitis, pay extra-attention to the red cells on the U/A, fire off that ANCA and anti-GBM ab. It is the job of the nephrologist to consider this diagnosis, if you don't no one will and a week later when the ICU and ID teams begin scratching their collective heads on why this patient is not behaving like a typical pneumonia you will have the reason and prevent a low yield and dangerous bronchoscopy because you will have the serologic evidence you need to get the renal biopsy for the win.

 The cryptic case of acute kidney injury starts off just like the banal case of acute renal failure, a rise in creatinine. If you open your eyes to the faint threads that don't quite fit the standard narrative you will be more receptive to seeing the clues you need to make that rare diagnosis.

Stay vigilant and stay hungry

The Sugar Fix: Chaper Two: Raising Cane

The Sugar Fix: Chapter 2: The birth of dietary sugar comes about 10,000 years ago in New Guinea. Johnson states that this moment is one that alters history as few other discoveries have.

Source Sugar Fix and USDA Economic research service

Sugar is a carbohydrate, one of three macronutrients in our diet (carbohydrate, protein and fat).
Table sugar or sucrose is disaccharide made of the joining of glucose with fructose. Lactose another disaccharide is made from the joining of glucose with galactose.

Sucrose. Note: glucose is on the left and fructose on the right

Fructose is he sweetest monocachide, about twice as sweet as glucose. Most high fructose corn syrup is about 50-60% fructose about he same amount of fructose as found in table sugar. Honey is 70% fructose. Almost all of the fructose we get in our diet comes from sweeteners added to foods.

The drive to eat sweet foods is inherent in our humanness. We don't need to be taught that fruit tastes better than vegetables. Johnson lays out a teleological argument that follows:

• sweet foods offer a survival benefit by promoting weight gain due to their caloric density.
• weight gain is enhanced by the fact that they don't promote satiety, so you can over eat, an advantage when food is in short supply and spoilage prevents storing leftovers
  
• the tendency of fructose to raise blood pressure may have offered a survival advantage to ancestors living on salt poor diets who suffered from chronic hypotension

He suspects that ancient humans ate only 15-20 grams of fructose a day (equivalent to two pieces of fruit) this compares to contemporary humans eating 70-80 g a day.

India was the first country to boil the juice from the New Guinea sugar cane to produce crystalized sugar.

Persian invaders brought home sugar and then the Arab invaders of the 7th century spread sugar from Persia to the rest of the Middle East.

The crusades brought sugar back to England in 1099.

Sugar was thought to have medicinal values and sold at pharmaceutical like prices. In 1319, sugar cost the equivalent of $50 per pound.

Sugar was one of the crops which supported the slave trade between Africa, North America and Europe.

England became a dominant producer of sugar and by 1700, the English were ingesting 4 lbs of sugar a year.

The democratization of sucrose accelerated following the discovery of the by which sugar could be extracted from beets.

In 1866 scientists in Buffalo invented a way to convert corn starch into sweet tasting corn syrup. Corn syrup is made of glucose chains of varying lengths. There is no fructose in corn syrup, so it is not as sweet as sucrose.

In the 1960s, glucose isomerase was discovered. THIS enzyme could convert some of the glucose in corn syrup to fructose ushering in high fructose corn syrup (HFCS).

HFCS is cheaper than sugar mainly because of the phenomenal overproduction of corn in this country. See the Omnivore's Dilemma. By the end of the 70's Americans were eating 10 pounds of HFCS every year.

In 1982 the US Government began to limit the amount of sugar which could be imported every year and by 1984 both Coke and Pepsi converted from sucrose to HFCS as the primary sweetener in their respective colas. The sweetwener in most colas is HFCS-55 which has 55% fructose only slightly more than sucrose, 50%.

Johnson states that another common variety of HFCS found in non-carbonated fruit juices is HFCS-42 (42% fructose).

He then claims that much of the harm from HFCS is not because it is anymore toxic than equal amounts of sucrose but rather that, its low-cost has resulted in more consumption.
This explains the expansion in the sizes an portions over the last 20 years. He points out the change in the size of a single serving of Coke. In the fifties it was 6.5 oz and now I am seeing 1 liter bottles (33 ozs) for sale.
The conclusion of the chapter has this wonderful sentence:

More to the point, the composition of basic nutrients that most people eat today is vastly different from what early humans consumed, or even what the typical American ate a century ago.

Patient missed a whole mess of dialysis in June

One of my dialysis patients suffers from chronic cryptogenic diarrhea. Because of the diarrhea she does not get volume overloaded or hypertensive. This week I received a call from the dialysis unit telling me she has missed 5 treatments in the first 3 weeks of the month. Sure enough the next day she ends up in the hospital, suffering the effects of chronic uremia. She had a bicarbonate of 4, a BUN of 120, and Cr of 16. Potassium was fine at 3.9 but the phos was 16.8 mg/dL. I don't think I have seen one that high, outside of rhabdo.

NCBI ROFL: a blog containing nothing but the most hilarious journal articles from PubMed

Check it out

The end of overeating

Looks like an interesting book. Nice write up in the NYT Well blog.

iPhone AT&T conspiracy theory

The recent behavior of AT&T regarding the upgrade from iPhone 3G to 3GS may shed light on how long we have to wait for a second iPhone carrier in the U.S.

No one outside of AT&T and Apple know for sure the duration of AT&T's exclusivity. In August of last year USAToday said the contract lasts until 2010 .

My thought is that if the exclusive contract ran out at the end of 2009 or by June of 2010 then AT&T would be behaving differently right now. Instead of telling people whoose contracts expire in a year to get lost for a year they would be rolling out the red carpet to extend their contract for another 2 or 3 years.

Eventually the exclusive deal will end and an early sign of that day will be AT&T offering current customers a deal to extend their contract. AT&T's current behavior signals that the exclusivity is here for at least a couple more years.

Myles Wolf is coming to speak at Renal Grand Rounds today

Wolf has been everywhere and is one of the premiere scientists elucidating mineral metabolism. He was the senior author on the article in the NEJM on FGF-23 and dialysis survival and the recent article on the survival advantage with phosphorous binders.

Just a quick review of FGF-23 so I'm not an idiot when this rock star nephrologist starts talking. (FYI don't let the clean cut pic above fool you, he came to the lecture in full rock-star fashion with the long hair, groupies (supplied by Genzyme) and everything)

FGF-23 is produced by osteocytes.

Klotho seems to be a required co-factor for FGF-23, such that mice that are Klotho deficient mimic the phenotype of FGF-23 deficiency.

FGF-23 increases renal phosphorous clearance by blocking Na-Phos reabsorbtion in the proximal tubule. FGF-23 also inhibits 1-alpha-hydroxylase, decreasing 1,25 OH-vitamin D.

Some of the biology is still a mystery. The highest density of fgf-23/klotho receptors are located in the distal tubule but the biologic effects stem from the proximal tubule.

FGF-receptor and Klotho are also found in the parathyroid gland but the exact role it plays is unclear. Some data points to direct stimulation of PTH and both molecules tend to rise together but this may be due to FGF-23 surpressing 1,25 OH D and secondary increases in PTH.

Increased phosphate and 1,25 vitamin D both stimulate the production of FGF-23. [Note Wolf provided data that phosphate levels do not increases FGF-23. He proposed that it is phosphate balance that is important, his supporting data included lupron treated patients bump their phosphorous by half a point but FGF-23 doesn't budge, I couldn't find this article on Google]. The Phex endopeptidase cleaves and inactivates FGF-23 so that is another control factor. [Wolf also discussed iron infusions causing phosphorous wasting due to excess FGF-23 ref pubmed related search]

Here it is

Where's my iPhone 3.0 software?

Phil told me it would be here on the 17th.

Getting another abstract (or two) ready for Renal Week 2009

We are racing the deadline for our ASN abstract. We have a great data set on geriatric patients in a structured CKD clinic. We need to define stable renal function. Our first try used the CKD stages. Our cohort is restricted to CKD 3b and 4. So stable was any patient who began and ended the study in the same CKD stage. This has been done in the literature, so there is some precedence but it doesn’t feel right to me.

Think about two participants in our study, both GFRs fall by 3 cc/min over three years, just about what the Baltimore Longitudinal Study on aging predicts. Patient A started with an eGFR of 31 mL and Patient B started with an eGFR of 33. These patients have the same clinical course and outcome but Patient A goes from 31 to 28 mL/min and hence from CKD Stage 3 to 4 while Patient B goes from an eGFR of 33 to 33 so his stage does not change.

I need a definition of stable renal function. You can help by filling this 5 question anonymous survey. We are looking

How would you define stable renal function:

Candidate A: Change in GFR less than 2 cc/min/yr (essentially 3x the average rate determined by the Baltimore Longitudinal Study on Aging).

Candidate B: Change of GFR of less than 20% from baseline to the end of the study

Candidate C: Change of less than 10 mL/min from the baseline visit

Note: baseline visit is the 1st contact with us with a GFR<45 mL/min(CKD stage 3b), we removed any patient who does not have a second eGFR < 45 at least 3 months before the initial measurement.

Dabble DB

Really neat demo of an online database.

I may need to try this.

DabbleDB

Online endocrine textbook

This looks pretty cool.

Here is the link to the section on kidney stones written by Murray Favus. On my brief overview it looks good.

Being in the textbook business in the era of free online textbooks, UpToDate and wiki's has got to be a world of hurt.

Renal stents for preservation of renal function with atherosclerotic renal artery stenosis

The annals has an article this week on renal stents and again they fail.

Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function

They randomized 140 patients with GFR <>50% stenosis (CT angio, MRA or digital subtraction angiography) with in 1 cm of the origin of the renal artery. They also excluded patients with uncontrolled blood pressure (>140/90) this was done because if patients randomized to medical management developed uncontrollable blood pressure they could cross over and receive a stent.

The end point was a persistant 20% reduction of GFR by Cockcroft-Gault for more than a month.

Results: No significant difference between the two treatment strategies.

The Kaplan-Meier curves confirm this. The top graph is the primary outcome and the bottom graph is primary outcome plus death:
Renal angioplasty resulted a variety of complications:

Two patients in the stent group died of procedure-related causes within 30 days after stent placement. In 1 of the patients, embolization of a perforated renal artery was required; the patient subsequently developed pulmonary edema and needed mechanical ventilation, and died of a massive ischemic stroke 3 days later. The second patient had perforation of a renal artery branch; the artery was embolized, but despite re-intervention, the patient went into hypovolemic shock and experienced the acute respiratory distress syndrome, and died of multiorgan failure after 1 week.

The most common complications after stent placement were minor and mainly consisted of hematoma at the puncture site (11 patients [17%]). In 1 of these patients, secondary infection in the groin required surgical reconstruction. The patient thereafter developed end-stage renal failure, pulmonary edema, and heart failure and died 6 months after the procedure. In 2 other patients, stent placement was complicated by false aneurysm of the femoral artery. Injury to the kidney or renal artery occurred in 5 patients; however, this was never associated with loss of renal function and additional intervention was never required.

One patient in the stent group who had repeated angiography required permanent dialysis after cholesterol embolism.

So another negative trial of renal artery revascularization. We are still waiting for the publication of ASTRAL, a much larger and more definitive trial. CORAL is another trial which is ongoing and will shed further light on this subject.

Important article on what drives the high cost of U.S. medicine

The Cost Conundrum

Will the UK courts squash scientific discourse?

This article about Simon Singh's battle with the British Chiropractic Association is frightening.

The consequences of letting the libel law loose on scientific debate are horrendous. Science proceeds by peer review. A researcher's colleagues must submit his or her ideas to scrutiny without fear of the consequences. If they think they could lose their homes and savings in the libel courts, however, they will back off.

For alternative therapists are not the only ones answering their critics with lawyers. NMT, an American health giant, is suing a British doctor for questioning one of its treatments.

Incredibly the BCA has won the first legal round.

The BCA sued for libel. And on May 7th Sir David Eady, a high-court judge, ruled, in a preliminary hearing, that the “natural and ordinary meaning” of the phrase (the relevant legal test) was that the BCA was being consciously dishonest and knowingly promoting quack treatments.

The key to the court case is a claim that chiropractic treatments for problems outside of backpain are bogus that Singh made in Trick or Treatment: The Undeniable Facts about Alternative Medicine, a book he coauthored on alternative medicine.

Advancing medicine and science is impossible if writers have to self-censor themselves when discussing scientific claims.

Nike+ iPod imprecision

I have been running off-and-on for the last 3 years (mostly off) and running regularly for the past 15 months. I love how lightweight it is the antithesis of biking or backcountry hiking with their emphasis on gear. Running is nearly completely free of equipment and gear. All I do is strap on my shoes, plug in the headphones and go. The exception to this is my Nike+ iPod pedometer. This is a cool gadget that consists of a sensor which goes in your shoe and a receiver which plugs into the 30-pin connector on the bottom of the iPod Nano. If you use an iPod Touch you don't even need the receiver.

I was blown away by the accuracy of the device and have been rediculously satisfied with this $30 gadget. Two events brought home how accurate the pedometer was: I ran a Cinco de Mayo 5k in Brooklyn with my sister a few years ago. The pedometer signaled 5k on the very footfall that crossed the line finishline. It was accurate to the step. Amazing:



I had a similar experience in the Detroit Marathon Relay in 2007. I ran a short segment from Downtown to Belle Isle. As soon as I crossed the timing blocks the iPod signaled I had reached my goal:



Last fall when I did the half marathon the accuracy fell a bit. It recorded 13.6 for a 13.1 mile route but I felt that 5% slosh was okay:



I had the same over estimate occur during the martian Marathon 10k. With the devic recording 6.5 miles for a 6.2 mile run. Again a 5% error:

What inspired this post was the new finding that in 2009 the error has swung in the opposite direction, now the Nike+ is underestimating my distance and speed. I first noted this during an 8.5 mile loop I ran with PBFluids reader and fellow nephrologist Steve Rankin. The Nike+ only recorded 7.98 miles:



Yesterday I did the Dexter-Ann Arbor half marathon and again the Nike+ iPod underestimated the distance and speed:

In the end it was only off by 0.6 miles over 13.1, so 5% but on my next run my Nike+ odometer will cross 1000 miles and its a little less satisfying thinking that I already crossed that milestone at some unrecognized time in the last month or so.


Update: Just discovered that the New York Times recently did a review of the Nike+iPod system.