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