January 26, 2023

My name is eric hoster i’m from ghent university in belgium and my talk on this first e-i-that meeting is on the furosemide stress test oops these are my conflicts of interests and they are um not really relevant for this this talk so i’ll leave you with that so what is the furosemide stress test well it’s it’s very simple it’s administering furosemide in patients

Who have aki and looking at urine output and if there’s urine output that’s good that’s a good sign it’s it’s indicating the kidneys are working and if it’s if there’s no urine output it’s not good so that’s something we all we do all the time in in in the icu um the the beauty of this test is that it’s um it it gives you a quite a complete picture of things uh

Happening in the kidney first of all the furosemide has to enter um the urine to to work in the in the thick ascending loop of henle and in contrast to what i believed and probably many of you believe is um the the furosemide is not entering the urine through the glomerulus furosemide and other diuretics are bound to proteins and they do not pass the glomerulus

So uh these these these diuretics they enter the urine um through the proximal tubular cells so they first have to be delivered at the proximal tubular cells by the afferent arteriole then they are picked up by the organ and organic anion transporter and secreted in the primary urine by the multi-drug resistant associated protein so two transporters that have

To be present and in action in the proximal tubal cells it is transported then in the primary urine up to the thickest ending loop of henle where it binds to the sodium potassium chloride co-transporter and it exerts its action so it it gives you a quite complete test of of different parts of the kidney um it’s in uh 2013 that ming chola standardized this

This simple test that i explained in the in the previous slides so what did they do a small study 77 patients it was part part of these were retrospectively collected data and part of these were prospectively collected data and this is the methods part of the of the study it’s a very simple study in patients with aki stage one or two um these were um exposed

Or or administered furosemide and if they didn’t have furosemide on beforehand it was a dose of one mil milligram per kilogram in bolus and if they had furosemides administered already they were administered one and a half milligram per kilogram furosemide and they looked at urine output and they found that when patients had the urine output during the first

Two hours after administration of 200 mils or more these were categorized as fst responsive and if it was less than 200 mils these were categorized as fsd non-responsive this um this graph shows you all so in the the gray bars are the patients who did not develop acute kidney injury stage three and the strike bars are are other patients who did develop acute

Kidney injuries stage three and you can see there’s a clear division your output is markedly higher in patients uh who who did not develop acute injuries stage three on the other way around it was markedly lower in patients who did who did develop acute kidney injury stage three they looked at several cutoffs and and time points and found that the two hour cutoff

Was the was the most optimal and when you plotted this in a roc curve the area under the curve was point 87 which is very good for a diagnostic test very very good sensitivity and specificity are under underneath in this in this table 87 and 84 again very good data or very good numbers for um sensitivity and specificity for a diagnostic test for such a simple

Diagnostic test after this um this this hallmark study in which the in which the furosemide trust test was standardized several others studied this this test and this is summarized in this systematic review and meta-analysis published this year by chanatol and in the top-hand sl part of the slide you can see the sensitivity and specificity of the different of the

Different studies and you can see there’s some variation as in every meta-analysis there there are some studies that that do not replicate the original data but um the the summary sensitivity of point 81 again is is impressively good and the summary specific specificity of 0.88 is again very good and the positive likelihood ratio which is kind of the auc rock is

0.5.45 which is again good how does the fst relate to other biomarkers for a prediction of aki severity are biomarkers such as ngal or the nephro check biomarkers that that have come up the last 10 years and and and we we read a lot of papers on these biomarkers and they they do fairly good so how does the does this simple fst test relate to these biomarkers

This was studied in the same data set as the at the hallmark study i i i showed you before and so on these similar on the same 77 patients the fst was evaluated and compared to 10 different biomarkers and you can see again the auc rock numbers and the fst is much higher the auc rock of the msd is much higher compared to the others 0.87 compared to the highest

Of them is plasma angle 0.75 so the fst does pretty well in in this in this setting so um could fst also predict need for rrt this was evaluated in this it is it is nice and elegant study in in thailand five thai icus randomized 100 and or sorry included 162 patients and and administered a furosemide stress test to these patients 44 of these patients were

Responsive so according to the test if they are responsive they they should not develop aki stage 3 and indeed a very low number of these patients evolved to need for rrt so 13.6 percent so it was not zero percent but it was a very low number uh compared to the patients who were non-responsive 118 were non-responsive and you can see there were two groups and i

Won’t go into the details of that but um at least 75 of these were treated with rt so if you’re responsive likelihood of needing rrt is low and if you are non-responsive the likelihood of needing rrt is quite high so the fst also gives you an indication on the need for rt later on again other studies evaluated this this topic also and here is the summary slide

From the same meta-analysis i showed you before sensitivity for prediction of rt 0.84 specificity 0.77 and again there are some there are some studies that that show outliers but but that these are pretty good numbers uh can we also use it um the fst to to to see if a patient um who is on crt needs continuation of crt so the typical scenario is crt stopped

For one reason or another maybe the circuit was uh was clotted or or there was a procedure going on for which the for which the crt secret was stopped and then there’s always the discussion should we restart this this procedure uh this therapy crt so this group from from netherlands name eagan they um they they they did a kind of an alternative version of the

Furosemide stress test they administered a continuous infusion of furosemide 0.5 milligram per kilogram per hour and they looked at urine outputs during the fourth first four hours and they found that patients who had no real recovery so the patients who needed another session of crt another circuit of crt these patients had a much lower urine output compared

To the patients who did not need another session of crt and again this was with a very high auc rock it has to be said that the number of patients in this retrospective study was quite low 25 patients so interesting data but i think they need to replicate it this brings me to my summary slide on the furosemide stress test it’s a super simple and cheap test pure

Smite costs i don’t know what how much is cost but it’s very very cheap and it has little side effects it’s uh it’s pretty good at predicting aki stage three in patients who already have api stage one or two and also pretty good in predicting use of rt in these patients and probably it can also help us in deciding whether these patients that are on crt need

Another session of crt afterwards but this these data are uh gathered on a small number of patients that need to be um we need extra data to to be sure on the on this on this statement and this brings me to myself to my uh to my last slide i thank you very much for your attention

Transcribed from video
The furosemide challenge test Eric Hoste By nsicu ru