NephMadness 2015: Final Four Results

Sudden Cardiac Death in ESRD versus sFlt1 in Preeclampsia
Winner: sFlt1 in Preeclampsia

6-1 split

sFlt1 in Preeclampsia will represent the Obstetric Nephrology Region in the championship of NephMadness 2015. This will be a match up of the acronyms (sFlt1 vs APOL1). SCD in ESRD had a great run in NephMadness, but all good things have to come to an end. Let’s review sFlt1. First off, sFlt1 stands for soluble fms-like tyrosine kinase-1 and is a splice variant of vascular endothelial growth factor receptor 1 (VEGF-R1). The initial report of sFlt1 demonstrated that its was not only is a marker but also an inducer of preeclampsia (in a rat model) from Maynard et al in JCI in 2003. When produced in high levels it acts as a molecular sink for VEGF. Therefore, sFlt-1 acts by inhibiting local VEGF signaling in target organs including the kidney, brain, and liver where VEGF is constitutively expressed. This finding ushered a new era in how people thought about the pathophysiology of preeclampsia. Working out the physiology also helped to shed light into the biology of VEGF itself. How will this important finding be translated to the care of patients with preeclampia? That is what we are all waiting for. The most logical therapy is just to remove sFlt-1 from the circulation. This has been attempted in an uncontrolled pilot study with just  a handful of patients.  What other potential therapies are on the horizon? sFlt-1 will be a team to watch in the future. How will they match up against a much newer discovery in APOL1? The biology of APOL1 is still being worked out. But, the potential is HUGE. Explaining and potentially reversing the high prevalence of ESRD in African Americans will be a game changer.

Comments from the Blue Ribbon Panel:

“I had a case of pre-eclampsia just last week that required termination. It was devastating for everyone. We just gotta do better than that. This gives us hope.”

“The molecular biology of sFlt1 heralds a new era in Nephrology care.”

APOL1 versus Tyrosine Kinase Inhibitor Toxicity
Winner: APOL1

5-2 split

APOL1 is one of the very few concepts that has made a return trip to NephMadness. It had a good run in 2013 and was the Regional Champion in the Proximal Tubule Vasa Recta Region, but couldn’t get past the HEMO trial to advance to the Final Four. After an off year APOL1 came back with a vengeance in the Genetics Region. In addition to making a return to the bracks of NephMadness, APOL1 is no stranger to the Nephrology Blogosphere. Some highlights:

• August 2010 Conall O’ Seaghdha, the selection committee member of the Genetics region was on top of the research as it emerged and covered it on the Renal Fellow Network.
• September 2010, Kenar followed with a nice description of the MYH9/APOL1 confusion with, “It’s not me, its the guy next to me” on Nephron Power.
• December 2010, Renal Fellow Network: Number 4 in the ranking of top nephrology stories of the year, APOL1.
• January 2011, Precious Bodily Fluids: APOL1 the best medical science story of 2010.
• December 2011, AJKDblog did a provocative poll regarding living kidney donors and APOL1 polymorphisms. Results and commentary here.
• November 2013, APOL1 makes a showing to the late breaking trials at Kidney Week. AJKDBlog is there.
• December 2013, APOL1 returns to top nephrology stories of the year.
• July 2014, Red Beans, Tulane’s Nephrology Fellowship blog posted questions on FSGS with APOL1 data.

With a social media resume like that, I think it’s time for APOL1 to cut down the nets.

Comments from the Blue Ribbon Panel:

“APOL1 is a natural selection, survival of the fittest mutation phenomena that may while be useful in Western Africa, seems to be disastrous everywhere else. It has an impact on so many renal diseases. Imagine if we could somehow target the effect of it! In previous blog entries I gave it a Nobel Prize, then an Oscar and a Grammy, and said it explained sun spots. It may even help the Cubs win a World Series, it is that big and powerful. Actually, who am I kidding, nothing is that powerful.”

“Personalized medicine through genetics may first enter into Nephroogy care through APOL1.”

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