By Joel Topf, MD - 19th Aug 2015 - Course previews

Diuretic resistance

This is the final video in our free teaching series on diuretics. Do you know what to do when diuresis is not sufficient? Well, you will definitely know after watching this video. It was taken from our brand-new Fluid and Electrolytes Masterclass!

In case you missed the first four videos of this series, you can find them here:
1. The philosophy of diuretics
2. Loop diuretics
3. Thiazide diuretics
4. Acetazolamide and the potassium-sparing diuretics


Video Transcript

[00:00:00] Sometimes, diuretics don't have the effect that you expect. Here's an example of a good diuretic response. This diuretic failure has two typical patterns. So, the first is just you give the drug and you get no response. The other is that you give the drug and you just get a real short response, so that you don't get enough diuresis over 24 hours.

[00:00:30] So there are two different responses for this diuretic resistance. If you have a short response, you want to increase the frequency that you give the drug and that could overcome that short response. You can even use a continuous drip or switch your diuretic to a longer acting diuretic to overcome this. This is typical of the diuretic failure we see in heart failure, liver failure, and nephrotic syndrome and usually 

[00:01:00] increasing the frequency is your best bet there. The other pattern of diuretic response is no or minimal response. Here, increasing the frequency doesn't help. You just get the same crappy response more often. This pattern of resistance is usually due to decreased glomerular filtration rate, renal failure or significant proteinuria. It is thought that the proteinuria that gets into the tubular fluid 

[00:01:30] binds up the diuretics, they're so prone to being protein bound. The best response to this type of resistance is to increase the dose. By increasing the dose, you can overcome this decrease in GFR. What I found to be effective is increasing the furosemide to 20 times the serum creatinine to get an effective dose. The last pattern of diuretic resistance occurs when you get distal sodium reabsorption to 

[00:02:00] compensate for proximal diuretic. An example would be acetazolamide. Even if the acetazolamide is highly effective and increasing downstream sodium, the kidney has a number of different opportunities to increase its sodium reabsorption and prevent net diuresis. This is one of the primary reasons that acetazolamide is considered a weak diuretic. This also occurs after extended exposure to loop diuretic. Patients up-regulate distal sodium reabsorption. 

[00:02:30] So, here's your loop diuretics, causes a lot of distal sodium delivery. The kidney responds by up-regulating sodium reabsorption. We can actually see hypertrophy of the distal convoluted tubule, on kidney biopsies, when they've been on loop diuretics. The response to this, to compensate for distal sodium reabsorption, is to block it with additional types of diuretics. So, here are the loop diuretics. There's the response with increased sodium reabsorption, 

[00:03:00] and then we compensate by either adding thiazide-type diuretics, potassium-sparing diuretics or both.