Friday, December 9, 2011

Diabetic nephropathy

I was invited to do grand-rounds at St John and was given no guidance on selecting my topic. I recently received a phone call from a long-time family friend, this man had literally changed my diapers, and he asked me to help a relative get bardoxolone. My group is participating in Beacon (the current phase II trial for bardoxolone) and though I am not one of the investigators I assured him that we would evaluate his friend. I couldn't guarantee he would get study drug rather than placebo or even qualify for the trial.

The whole event shocked me. I had no idea that the results of the Bardoxolone study had slipped beyond the geek fringes of nephrology. It reminded me of a story that Judah Folkman told. He came to Indiana University to collect an award and give a lecture, shortly after a NYTimes profile. In that front page story James Watson (yes that James Watson) said Folkman would cure cancer in two years.

Judah told the story that he was getting phone calls from strangers and friends asking for his miracle cure and was heart broken because he had nothing to offer them. At that stage his drug was only for mice.

That's Judah and me following the afore mentioned lecture in 1999.
Getting that call from my friend gave me the same sort of Folkman moment. I never thought people would be calling me trying to get experimental therpy. So I decided to talk about Bardoxolone.

As I started my research I became concerned that patients randomized to bardoxolone developed increased albumniuria.

Some patients tripled their albuminuria! The drug increased GFR, but the increased albuminuria could not be fully accounted for by the improved function.

ASN Kidney Week fell 10 days prior to my Grand Rounds so I planned on grabbing some good ideas at the meeting. On Friday I went to Kidney Disease in Type 2 Diabetes: New Insights. There were four lectures. The last two were homeruns.

Dr. Bruce Perkins was perfect for my talk. He spoke of how albuminuria is not a great surrogate end-point for diabteic nephropathy studies. Bad outcomes often follow a reduction in proteinuria.

I used my iPhone to record the audio and took pictures of each slide with my Nikon (this was before I learned that ASN did not want attendees taking pics of the lectures. WTF). When I got home I grabbed the best thoughts from his lecture and made it the cornerstone of my talk on diabetic nephropathy, bardoxolone, and a more modern view of albuminuria.
Thanks Dr. Perkins.

The lecture was a little light, I finished in 45 minutes and used some filler from my Diabetic Nephropathy 2009 lecture. Before I use the lecture again I would add some of the points from Andrew Bomback's excellent lecture, "RAAS Blockade: More is better? Yes. No. It depends."

Here is my PowerPoint (58mb) and PDF (51mb).
Note to self: the Helvetica Neue UltraLight, didn't project so well.

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