“What is man, when you come to think upon him, but a minutely set, ingenious machine for turning with infininite artfulness, the red wine of Shiraz into urine?”
Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.
[The inability of acetylcysteine to prevent dialysis or mortality] maybe because acetylcysteine alters creatinine handling in the proximal tubule. Acetylcysteine, actually accelerates the excretion of creatinine resulting in decreased serum creatinine.
After Tepel published his original work on acetylcysteine in 2000 everyone went a little crazy drinking the Mucomyst cool-aid. Here was a cheap, safe and already approved, remedy to the pervasive problem of contrast nephropathy. Everyone was so drunk with the excitement that they didn’t note that the 85% reduction in contrast nephropathy was not associated with a reduction in the need for acute dialysis or a reduction in patient morbidity and mortality.
In 2004, Hoffmann Et al. published the above quoted article which showed a modest but significant reduction in serum creatinine following ingestion of acetylcysteine. This seemed to me to be the best explanation for why a therapy could prevent an increase in creatinine but not prevent dialysis. (Data on the lack of prevention of dialysis from Miner et al. Am Heart J 2004.)
Apparently the patron saint of contrast nephropathy, Richard Solomon, recently reevaluated this theory and found it lacking. He took 30 patients with GFR < 60 mL/min and given 1,200 mg of acetylcysteine every 12 hours for four doses. Creatinine and cystatin C were measured at baseline, 4 and 48 hours after the last dose of acetylcysteine. They found:
Serum creatinine and cystatin C levels did not change significantly at either 4 h or 48 h following the last dose of NAC compared with the baseline values (Table 2; Figures 1 and 2). However, a small but statistically significant reduction in the ratio of serum creatinine to cystatin C was observed at 4 h but not 48 h.
- Phosphate nephropathy
- Nephrogenic fibrosing dermopathy (I’ll never get used to calling it nephrogenic systemic fibrosis because, despite what the literature states, all five patients I have seen had purely dermatologic manifestations)
- Contrast nephropathy
This is time that will pay major dividends down the road.
The mayo clinic libraries have posted a series of screencasts that will make you better at PubMed. Spend the time.
In 1996, a year before returning to Apple, Fortune interviewed Steve Jobs. When asked what he would do to save Apple he explained:
If I were running Apple, I would milk the Macintosh for all it’s worth — and get busy on the next great thing. The PC wars are over. Done. Microsoft won a long time ago.
At that time, this quote was like a dagger in my heart. At the time Apple was flailing. Windows was rocking and the drumbeat of the end was getting louder. To hear the creator of the Mac declaring the war lost was heart breaking. I chalked it up to an off-the-cuff, spoiled-grape quotation.
Later, after Steve came back to Apple I began to feel vindicated in my opinion. Steve didn’t act like he was “milking the Macintosh.” In no way could I see his actions as just “milking the Mac.” Check out this video of Steve at the 1997 MacWorld. I see no indication of the hopelessness that the PC wars were over (Steve enters at 5:30):
So from the moment Steve re-enters the PC picture, he restokes the PC wars. He introduces the iMac. He successfully recreates the NeXT operating system as OS X. And, though he had phenomenal success growing Apple’s computer business, none of that really fits the bill of The Next Insanely Great Thing.