Okay, thank you.

So when Felix asked me to come and give this talk, I was very honored and pleased to be

able to come.

And he asked me to basically use the template of the talk that we give with our first-year

renal fellows.

So my talk is going to be a little more clinically oriented, but I'll try to pepper in some research

components to make it interesting.

So my first thing is that, as you're going to hear a lot from Sharag in his later talk,

is that we give this term acute kidney injury in patients, but in fact what we use to define

it has nothing to do with injury, but rather to do with failure of chlamyular filtration.

We don't actually use an injury marker to define acute kidney injury, and I think that's

one of our failings still.

And so that clinical definition for acute kidney injury is typically based on a rising

creatinine, and we have certain cutoffs that have been defined by clinical studies that

have suggested that even these small rises in creatinine correlate with differences in

outcome in the patients, and therefore become clinically a viable model to think that that's

a functional effect.

The causes of this in patients are quite variable.

The most common ones that we see in the hospital are typically some form of hypoperfusion of

the kidney to Kai's point, and I'll talk about this more in a little bit.

That makes up roughly 50 to 70 percent of the patients that we see with these kinds

of acute rises in creatinine.

Medication-induced tubular injury is the next probably most common player, and Mark Parazella

is going to be giving us a talk about that shortly.

I don't know if Mark's including radio contrast in there or not.

So radio contrast, if you add these together, this becomes the most dominant second cause

of radio contrast plus other medications.

And then glomerulonephritis and acute interstitial nephritis make up another smaller part along

with obstruction, and I'll talk about all of them briefly.

So why is the kidney... So I'm from West Virginia, a small state in the United States

where coal mining was very popular, not so much anymore, and we had the term the canary

in the coal mine, which was this bird they would put down there to detect the methane

gas when it fell off its perch and died.

We knew you had to get out of the mine because there was a lot of methane.

So the question is why is the kidney such an indicator of hypoperfusion?

We often see patients with hypotension, sepsis, other diseases that will develop acute kidney

injury, but they don't develop a stroke, they don't develop a heart attack, they don't

usually even develop liver failure.

It's really predominantly the kidney.

And as Kai alluded to, we think it's a lot to do with the architecture and the function

of the kidney, and that combination is difficult.

So the first of those is that the kidney has a high metabolic demand, and so here's my

little nephron structure.

So here's the aphronotaryl bringing blood into the glomerulus, the aphronotaryl bringing

blood out, and here's proximal tubule, thin limb, thick limb, distal convoluted tubule,

and collecting duct.

So if you remember from the talks earlier in the week, which I unfortunately missed,

but looking over the list, I have a feeling you've got a very good sense of all of this.

But just to kind of bring it into focus, you're filtering, depending on, Peter probably told

you 180 liters a day, whatever, you're filtering a lot of your plasma.