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Dr. Anton Titov, MD.: Are there laboratory criteria, or certain clinical signs that help to determine if diuretics are used correctly in heart failure, especially in hypertension? Of course, volume overload criteria are important. But is there anything in addition to that? Yeah, I think that's a great question. And in heart failure, that's been one of the holy grails, which is, how do you monitor patients? I think there are two different types of biomarkers that supplement our clinical exam. But how we define decongestion still is very much an art. And there is no one test that we can use definitively other than if you put a central venous line in and measure the central venous pressure, or a Swan Ganz catheter. And there have been randomized controlled studies showing that for most patients, that doesn't add value. So, we still try to assess these things, non-invasively. So, the approaches that can be used include measurement of BNP or B type natriuretic peptide. And that's not a bad test. So very long time ago, [in 2002] the so-called "BREATHING NOT PROPERLY" clinical trial, in the New England Journal of Medicine showed that the measurement of BNP was a very good test for determining whether patients coming into the emergency department had pneumonia versus heart failure. Dr. David Ellison, MD.: And so, I think it's still a very good test. In those situations, there is some data that goes back and forth about whether measuring BNP levels is useful therapeutically in acute decompensated heart failure. But it also is very clear that a decline in BNP levels as one treats heart failure is a very good prognostic sign. So, we measure it all the time, and I look at it. But it's not the definitive test. First of all, because patients with kidney failure have higher BNP levels, even when they are not congested with fluid. And second, people who have chronic heart failure, their BNP levels can be chronically high. And it's much harder to interpret. So that is a test that's used commonly. I think it is useful. But it's not a silver bullet, it's not a perfect way to assess patients. In terms of other tests, well, right now we use a lot of so-called point of care ultrasound. And that's a very good test. Dr. David Ellison, MD.: And so, one the cardiologists will do echocardiograms by which they can assess the ejection fraction and the filling of the heart. And that's really important to know. I would just mention parenthetically that we know a lot about how to treat patients with heart failure with reduced ejection fraction, we know much less about how to treat patients with heart failure with preserved ejection fraction. So that's really an important differential. But in terms of congestion, we can both look at the neck veins with both our eyes, but also with ultrasound. And very commonly now we also use ultrasound to look at the inferior vena cava, the collapsibility of that. And that helps because if you have a patient with a creatinine that's going up, you are giving a lot of diuretics, you want to know whether that's because you really given them too much, or whether you still need to push ahead. Looking at the inferior vena cava can be a very useful part of your assessment of the patient. So, we really look at all of those different things. And then finally, in terms of the creatinine rise, as I mentioned, at least experimentally, it's very clear that we can assess kidney damage, whether the patient has moved from simply reduced kidney perfusion to actually kidney damage by using these biomarkers in the urine like KIM-1 or NGAL. And these biomarkers can tell us whether there's been kidney damage. But frankly, so can just looking at the urine. And one of the things that we do as nephrologists is we do a careful microscopic exam and see whether there's evidence of kidney damage. And that can be very useful in these kinds of situations. So unfortunately, we still don't have a magic test that tells us the answer about heart congestion, at least for most patients. Dr. David Ellison, MD.: And so, we ended up using all of our tools, both our history, our physical exam, devices, like an ultrasound device, and also biomarkers like BNP to try and get the best possible assessment of the patient's volume status.