NC 2020.09.11 Dr Belcher Clinical approach to AKI
October 16, 2020NC 2020.09.11
Dr Belcher - Clinical approach to AKI
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- 00:00Afternoon everyone. In there. Alright. So
- 00:09today we're doing a clinical
- 00:11approach to acute kidney injury,
- 00:13and that of course, is.
- 00:17Acute kidney Some of this is going to
- 00:21be a bit of a rehash from last week,
- 00:25so little different,
- 00:26but you have heard some of this before,
- 00:29so this is acute kidney being injured.
- 00:32Start with the case, so Once
- 00:35Upon a time 23 a man with a past
- 00:40medical history significant for plague
- 00:42and multiple spear wounds presents to your
- 00:46igora complaining a decreased urine output
- 00:49and lower extremity swelling, he was,
- 00:52you will say to help until five days ago,
- 00:56and he's bitten by and ask.
- 01:00Please check the level of his humor.
- 01:03So you write your note medications
- 01:05he's taking various herbals, an exam.
- 01:07There is effective fluvium laying
- 01:09up on him and he is separating.
- 01:12Fang wins on his calf with Adima.
- 01:15You diagnosed him with a snake bite
- 01:18and resulting acute failure of urine.
- 01:21Prognosis will depend on whether
- 01:23you develop polyurea.
- 01:25Plan is to give him a amero enema and warm
- 01:28compresses and late a sacred Reno, NV.
- 01:31This is from about 5000 years ago.
- 01:34A renal carving very historically correct.
- 01:37As you can
- 01:38say. Turkey so little history
- 01:40of acute kidney disease impact
- 01:42that we're talking about here.
- 01:44So all the way back 400 BC do some
- 01:47recognized causes of acute kidney injury.
- 01:49So inflammation,
- 01:50crush cooling of the kidneys.
- 01:52Then we built into poisonings or
- 01:54getting the toxic property breaking
- 01:56in the Kappel Aries inflammation
- 01:58humours corrupt corrupt beverages that
- 02:00might be a little more liver disease,
- 02:03drugs causing inflammation,
- 02:04scorching the sun and biting of the Serpent,
- 02:07and then finally around 1400.
- 02:09The recognition that systemic diseases
- 02:10can manifest as acute renal failure.
- 02:13So some of the symptoms
- 02:15and course I some of the highlights.
- 02:18Some of the big names, and in medieval
- 02:21nephrology and 280 is of pre medieval.
- 02:24I guess Rufus API associated nausea,
- 02:26anorexia, dizziness, vomiting shops,
- 02:28hypo thermia and if you have
- 02:31long anuria death and 400 we
- 02:33have or videos with two phases.
- 02:35The Algarin Poly Eric.
- 02:36If the Poly Rick does not
- 02:38occur that results in death.
- 02:41We all see that in a daily basis.
- 02:44I then 450 urine.
- 02:45This is called.
- 02:46This is polyurea and recurrence
- 02:48of concentration signals recovery.
- 02:49So if you get polyurea and concentration in
- 02:52the urine again that is a sign of recovery,
- 02:55which indeed is quite astute.
- 02:57And So what we look for today.
- 03:00It's 500 and we develop uroscopy,
- 03:03so the study of yarn as a means of examining
- 03:06Acuna fair or looking at the volume.
- 03:09The color smell, the taste.
- 03:11I would add we should add that to
- 03:13the Peters taste testing with all
- 03:16the drugs and the concentration and
- 03:19these are some of the big names.
- 03:21Really the kind of the founders of
- 03:23the art of looking at the urine.
- 03:26And how many in the modern day master
- 03:29of looking at the year of your Arizona,
- 03:31whatever, he could actually look you're
- 03:33comparing to our general knowledge,
- 03:35sharing or trellis up there
- 03:36you can see the results.
- 03:38It's the strength is in the mustache.
- 03:40Area.
- 03:45Treatment so that then there are
- 03:47a lot of ideas about treatment.
- 03:49They got marrow enemas.
- 03:51They gave died and purgation so this
- 03:53is actually an interesting is extra
- 03:56renal dialysis giving people things
- 03:58that cause diarrhea and vomiting and
- 04:00clearing urea through the elementary track.
- 04:02One day of fasting, then warm water,
- 04:05no diuretics are in all of
- 04:07your face interesting.
- 04:08Early fighting humours,
- 04:09or at least unused unleash
- 04:11excessive solid loss.
- 04:13Milk Bass High Herbal enemas,
- 04:14high enemas are no good.
- 04:16All sorts of things here,
- 04:18see urchins, cinnamon bread,
- 04:20bread,
- 04:20diet of birds,
- 04:21drydocks dung and drunk a spoonful
- 04:23a day they even eight perinephric
- 04:25factor game they strengthen
- 04:27some panels in Australia,
- 04:29but this is ridiculous right?
- 04:30Look at these things these these these
- 04:33ignorant troglodytes what are they
- 04:35doing there eating marrying marrow
- 04:37enemies or eating birds and sea urchins.
- 04:39Everyone knows now in the modern
- 04:42scientific area with all our advances.
- 04:44The treatment for API.
- 04:45It's a boy,
- 04:46never toxins and optimize volume sets,
- 04:49so we have indeed come along way from
- 04:51these these foolish remedies to it.
- 04:53A scientifically grounded Neil as of today.
- 04:57OK,
- 04:57so back to the future 2120
- 04:59year old man again.
- 05:01Now with a significant history for
- 05:03nut allergies and gluten sensitivity
- 05:04and carpal tunnel syndrome.
- 05:06Video game playing presents with decreased
- 05:08urine output and lower extremity swelling.
- 05:11He was his usual state of
- 05:13problems with four days ago.
- 05:15Leftover sushi in his dorm is P1.
- 05:17Take his poor you do with the facility.
- 05:20Check is humorous,
- 05:21but you don't.
- 05:22Instead,
- 05:23you order everything else,
- 05:24but you can.
- 05:25This isn't even close to the rest
- 05:28of your night with the rest of it is an epic,
- 05:31so his meds he's taking various
- 05:33herbal's without the prescription type.
- 05:34He's palamas argic, he has a motion edema.
- 05:37Lapse crannies 1.7 Is this acute
- 05:41renal farewell? This is 2001,
- 05:43so that depends on your hospital,
- 05:45whether in fact he has acute
- 05:46renal failure based on that.
- 05:48This again is still to help pay
- 05:51some development of Polyurea.
- 05:53Land hours avoid harm, wait,
- 05:54watch and hope and Dialyzed as needed.
- 05:57So we've come from are carved kidney
- 05:59stone to a fancy modern house machine,
- 06:02but still not much in
- 06:05between therapeutically.
- 06:06So kind of a little bit now in the
- 06:08history of the diagnosis vacation.
- 06:09So he said this gentleman was gravity
- 06:11of 1.7 in 2001 whether he had acute
- 06:14renal failure as it was a known was
- 06:16going to be dependent on where he was.
- 06:18There's a nice paper from John Kelemen.
- 06:20Such wiper back in 2002 looking at the
- 06:23definitions of API in the literature back,
- 06:25I say I bet it was a wrap.
- 06:27Those over 35 definitions publisher
- 06:29that I'm with no consensus in
- 06:31some of these you have an absolute
- 06:33increase or kind of had to buy at
- 06:35least one 1.5 some of them you had
- 06:37a present increase from baseline,
- 06:39so you at least 25% of the 50%.
- 06:41Some out of certain thresholds,
- 06:43you're crapping her eyes at
- 06:45least above 2 or about 2 1/2.
- 06:47And someone we actually needed
- 06:48dialysis to be termed as actually
- 06:50having acute renal failure and meant
- 06:52to have the need for acute dialysis.
- 06:54So obviously incredibly heterogeneous here,
- 06:55covering in vast range of severity
- 06:57of disease,
- 06:58and if you're trying to look
- 06:59at this from a public health or
- 07:01everything logic standpoint,
- 07:03it's impossible to look into these
- 07:05studies and combine patients,
- 07:06one of whom is AKA because the crowning
- 07:08roasted by 25% from the baseline
- 07:10one of 'em is API because they need
- 07:12dialysis at any sort of consensus.
- 07:14Analyzing those together.
- 07:15What is the values from the baseline?
- 07:18What is the baseline?
- 07:19There's no definition.
- 07:20There is a fun little study.
- 07:21They basically took these these definitions
- 07:23and graded them in terms of stringin.
- 07:25See with the further you over here kind
- 07:27of the harder it is to reach the API
- 07:30threshold and then look at mortality.
- 07:32And as you would expect,
- 07:33the more the more stringent your definition.
- 07:35The worst outcomes are.
- 07:36But these are definitely apples and
- 07:38oranges or apples or CNC urchins
- 07:40that you're trying to compare.
- 07:41So 2004 we move towards standardization
- 07:43with the rifle criteria,
- 07:45which all know,
- 07:46breaking API down not just by
- 07:47a minimal threshold,
- 07:49but then breaking in severity
- 07:51stages with a minimum here of the
- 07:54risk of branding rising by 50% from
- 07:56baseline or GF are decreased by 25%.
- 07:58Important that the rifle and cannon
- 08:01KD go that one still showing a minute.
- 08:04All that urine output criteria as well.
- 08:06And if you have actual accurate urine output,
- 08:09works just as well as crap.
- 08:11Adjusted sensitive diagnosis is just as good
- 08:13for predicting short and long-term outcomes,
- 08:15perhaps even better potentially.
- 08:16The problem, of course,
- 08:17is getting accurate hourly urine output,
- 08:19which is essentially impossible
- 08:20on the floor and the ICU.
- 08:21It's better and people have a fully,
- 08:23but even then when they're off of the floor,
- 08:26protest and stuff you could lose track of
- 08:28this so we don't talk about it as much.
- 08:31They're not going to put out here,
- 08:32but recognize that it is significant.
- 08:34Not that you have to dial eyes,
- 08:36someone when you fall in the middle of
- 08:38the night 'cause they're not peeing.
- 08:40We've all had that say whether laps
- 08:42are finding by requiring them.
- 08:43Sunday, July is in them,
- 08:45but they just certainly an ominous
- 08:47sign that worse things are coming
- 08:49down the traffic stop making sure.
- 08:51So the model criteria very similar.
- 08:53We have rifle and we have a Canon.
- 08:55We have KD go.
- 08:57All three of them have a minimum threshold
- 08:59for API and then all of them have the stages.
- 09:02The stages are really important
- 09:04for research purposes.
- 09:05Day-to-day practice you don't
- 09:06use the stages for very much.
- 09:08What is important.
- 09:09Also studying the ministering where
- 09:11this came from is the minimum
- 09:13threshold which is rise of either
- 09:15.3 or 48 hours or 50% / 7 days.
- 09:17Just let me know the baseline
- 09:19and KD go which is the.
- 09:21I can send this one that we use
- 09:23and the important thing here based
- 09:25on all those past definitions we
- 09:27mentioned is the sensitivity of it.
- 09:29So it rise of crowding.
- 09:31.3 a sensibly is not very much and
- 09:33many of the attendings we're watching
- 09:35this now or back when your residents at all.
- 09:38You're all All Star,
- 09:40fantastic residency,
- 09:40Dolgun Internal Medicine.
- 09:41You were thoughtful and you wrote these
- 09:43big fantastic notes with discussions
- 09:45of antibodies and infectious disease.
- 09:47And all this stuff.
- 09:48And then even budding apologists, if the
- 09:50patient scratching a few days ago has been.
- 09:53.8 and now is 1.1.
- 09:54It's very possible you didn't write
- 09:56a Ki or whatever you call it then,
- 09:59as one of the topics to be discussed,
- 10:02this sensitivity really
- 10:03wasn't recognized by then.
- 10:04Certainly if someone rose larger amount,
- 10:06he might talk about it,
- 10:08but it's really only in recent years
- 10:10that people have seen the importance
- 10:12of what would be otherwise dismissive
- 10:14small changes in creatinine.
- 10:16I think associations,
- 10:17at least significant hard albums,
- 10:19so
- 10:19there's positives are different.
- 10:20OK, so this is just one
- 10:22of the many studies looking at that where
- 10:25these numbers came from the study from new.
- 10:27Some of these are all about 10 years old now.
- 10:30Very large study looking at patients
- 10:32hospitalised with either no changing
- 10:33Pratt need or rising cracking and
- 10:35look at long-term development.
- 10:36If you start he and mortality is that
- 10:38the 10 years or so and patients who
- 10:41had to change this is just a .1 rise.
- 10:43These patients did roughly the same,
- 10:45but as soon as you get a change of .2
- 10:48anywhere in the course of your hospital stay.
- 10:50You start seeing an increase in
- 10:53the incidence of dialysis and death
- 10:55over the following ten years .2.
- 10:58This is absolutely nothing.
- 10:59Again, this is not at all to
- 11:01say it is constant.
- 11:02If you're not dying because of crappy.
- 11:04Went from 1.2 to 1.4,
- 11:05but it's a recognition of the kidneys,
- 11:08are very sensitive,
- 11:08kind of online biomarker for overall end
- 11:10organ perfusion and the feel ill health,
- 11:12inflammation,
- 11:13everything that can cause these minor
- 11:15changes also affecting other things
- 11:17elsewhere and kind of being the Canary
- 11:19in the coal mine for how things
- 11:21are going overall physiologically.
- 11:22And this is not just looking
- 11:24at has racing thoughts here,
- 11:26even at .1 and increase has arranged
- 11:28for dialysis and death out over 10
- 11:30years and increasing as you like to see
- 11:33stepwise up here and will come to a minute.
- 11:35We've chose .3 Edgewood,
- 11:37the one we're going to sign into.
- 11:39Healthy's definitions based on.
- 11:40This is looking at graphically,
- 11:42so change the crafting.
- 11:43None point one point 2.3 or
- 11:45more than .3 overtime.
- 11:47After 10 years I'm very noticeable increase
- 11:49in the incidence of dialysis and death.
- 11:51If you look at the Y axis,
- 11:54these are not large changes,
- 11:55so always look at the Y axis on
- 11:58the graphs you're looking at,
- 12:00but very,
- 12:00very minor changes in creatinine
- 12:02having statistically significant
- 12:03associations with hard outcomes.
- 12:06OK, so people saw this and
- 12:08they said OK We Gotta, we
- 12:10gotta do something about this.
- 12:11These are these are very
- 12:13unrecognized associations.
- 12:13These minor changes in creating
- 12:15comedic chaos in the definitions.
- 12:17Everyone follows API which we want
- 12:18to call it so they need to come.
- 12:21They came together in the city,
- 12:23in Italy this beautiful city.
- 12:24They have brought all the big players
- 12:26and all the families in which states
- 12:28in the thing and they need to bring
- 12:31all the people who have sway and
- 12:33influence who everyone listens to it.
- 12:35They bought.
- 12:36So they brought the five.
- 12:37Families in the Kunio stretches.
- 12:40Of course,
- 12:41the Corleones and these are the ones
- 12:44are forcing apology not so interesting.
- 12:48Folder CR and of course,
- 12:50these funds groups came together in
- 12:51Italy and this is where they came up
- 12:54with the consensus with the rifle criteria.
- 12:56And once that came out once one
- 12:58concession's statement comes out,
- 12:59everyone else wants to play along too,
- 13:02and so it can soon followed.
- 13:03And then you go.
- 13:05Made for new nomenclature.
- 13:06So acute renal failure had been the
- 13:08term people have been using and the
- 13:11idea was to switch this to AI and Lloyd
- 13:14actually talked about this last week.
- 13:16As to why this was.
- 13:18And the main reason was money,
- 13:20right?
- 13:20So when when someone asks you why
- 13:22something question in the hospital
- 13:23and you don't know the answer,
- 13:25which theatregoers should give?
- 13:28So next year round to know the answer.
- 13:31Now, even better, it depends.
- 13:32It depends if someone actually why
- 13:34something happens outside the hospital
- 13:35and you don't know the answer.
- 13:37The answer is always.
- 13:38Money money right so as like mentioned,
- 13:41apology,
- 13:41unlike some of the other subspecialties,
- 13:43doesn't have a lot of extramural.
- 13:45Meeting 9 H funding we don't
- 13:46have the financial equivalent of
- 13:48American Heart Association or
- 13:49National Cancer Foundation an,
- 13:51especially if you're in a player got
- 13:53very little in the way of funding
- 13:55research than people thought.
- 13:56Well, people know what part is?
- 13:58They know what cancer is,
- 14:00what the heck is arenal right?
- 14:02We called it a kidney.
- 14:03OK,
- 14:04I've got kidneys.
- 14:04Maybe I want to fund research
- 14:06for that and then failure is just
- 14:08failure is just too pejorative.
- 14:10Your kidneys have failed.
- 14:12It's done, it's over, why bother?
- 14:14Grave injury though injury OK I can
- 14:17work with injuries like Kitties got
- 14:20a sprained ankles right so renal failure.
- 14:23Kidney injury,
- 14:23so they thought this might spur some
- 14:26more money for research as it happens,
- 14:28not really, but API is what we have now.
- 14:32The question is, is this more accurate?
- 14:35Is this a better term?
- 14:37Ah.
- 14:39An answer is Yeah Alright,
- 14:41because The thing is acute
- 14:44kidney injury implies.
- 14:46Injury by structural physical damage,
- 14:47and since we're defining API
- 14:49based on changing creating
- 14:50which that filtration marker,
- 14:52the fact that they have a drop in the
- 14:54GF are by no means necessitates that
- 14:57they have an actual kidney injury.
- 15:00So you can have a Ki without kidney injury.
- 15:03You got API seen a injury.
- 15:05This is really, really perhaps
- 15:07easier to understand than a RF,
- 15:09but not really anymore.
- 15:10Actually at diagnostic accuracy.
- 15:11So Lloyd always loved the term F,
- 15:14which I think is fantastic.
- 15:15So this is a cute filtration failure and
- 15:18this is really what we're talking about.
- 15:20Here is cute.
- 15:21Rising cragging simply signifies
- 15:23an acute fallen GF are.
- 15:24It doesn't specify whether that's due
- 15:26to injury, hyperperfusion or whatnot,
- 15:28but if a RF was too esoteric than
- 15:31app is not going to catch on.
- 15:33But that's really what
- 15:34we're talking about here.
- 15:37OK, so moving
- 15:38on a little bit to the Epidemiology,
- 15:40this is a paper is not just US is worldwide,
- 15:43but I like it 'cause it's just
- 15:45incredible number of studies in patients
- 15:47looking to overall incidents of API
- 15:49and then stages in hospitalizations.
- 15:51This does very similar country by
- 15:53country so when you blend it all like
- 15:55this and give a little bit distorted
- 15:57picture but certainly showing that guy
- 15:59is very common houseflies patients
- 16:01as you would expect from stepwise.
- 16:03Most common word is going to be for
- 16:07mildest variance. And then mortality.
- 16:09Here again, this is this is worse
- 16:12than we I think.
- 16:13Typically see in practice here,
- 16:15but increasing stepwise of severity
- 16:17even in the states Dallas surprising
- 16:19API is associated with a very high
- 16:21mortality stage three as well.
- 16:23Very common and very severe problems.
- 16:26So where do you live?
- 16:28Everyone is and I
- 16:30thankfully what happens if you have
- 16:32any kin recover or not.
- 16:34So this is a paper sewing kind of
- 16:37the different tracks you could take,
- 16:40so this is someone coming in without
- 16:42any baseline chronic kidney disease.
- 16:44Who has AI? You could recover all the
- 16:47way back to your baseline here and
- 16:50then go on to live your normal life.
- 16:53You could recover partially and then
- 16:55progress at a steeper or even more sleep.
- 16:58The client bar going forward,
- 17:00or you can never recover from yugioh far,
- 17:02and this is again showing someone
- 17:04see Kitty with the same thing.
- 17:06So even in patients who fully recover than
- 17:08what they're trying to show is kind of
- 17:10these changes in these slopes here is there.
- 17:12If you recover backer was was a sensible,
- 17:15your baseline crafting very commonly,
- 17:16especially for talking about
- 17:17the structural form of API,
- 17:18you're going to be left with
- 17:20some self clinical injury.
- 17:21You're going to have some scarring.
- 17:22Gonna have some fibrosis.
- 17:23You have a loss of what's known
- 17:25as your renal functional reserve,
- 17:27which is kind of the backup GF are that
- 17:29can be kicked in what you feasibility.
- 17:31Increase your email profusion in
- 17:32the setting of a protein mode.
- 17:34So even though you come back
- 17:36to your baseline creatinine,
- 17:37you're at a higher risk of having subsequent,
- 17:39more rapid loss in the development of CD
- 17:41that you never had API in first place.
- 17:43Even floor covering isn't necessarily
- 17:45really full recovery.
- 17:48I'm looking at the
- 17:49risk of that's the paper
- 17:51from from Steve Coca.
- 17:52Looking at the hazard ratio
- 17:54slid element of either CKD&E,
- 17:56SRD and wrestling with a bunch of these.
- 17:59Some of the biggest studies looking
- 18:02at API prevalence of 10 years ago,
- 18:04but the psychosis are being formulated
- 18:06showing a significant risk.
- 18:08This is of Dinovo CK di and then he
- 18:10SRD amongst patients who already
- 18:13had cecati patients who recover
- 18:15significant risk of future.
- 18:17Having had lived through AI.
- 18:19So even a transient issue has
- 18:22not been anything.
- 18:24OK, so that's kind of the Epidemiology.
- 18:26Now we're getting into causes an for me.
- 18:28I always love, AKA.
- 18:29I think they asked me to do this.
- 18:31Stop before the finer things.
- 18:32More better console to get as a fellow
- 18:34and you get to go to the chart and you
- 18:37default with the chart and dig through it
- 18:39and come up with all these bright ideas.
- 18:41But there's a lot of different possibilities
- 18:43and it's important not to miss anything.
- 18:45And so the way I always try to do it was to
- 18:47try to kind of fly through the body right.
- 18:50And so you kind of think of all the
- 18:52ways that the Kitty could be at damage,
- 18:54or at least the filtration can drop.
- 18:56And you kind of start in the heart
- 18:58as the blood has to get to the heart
- 19:00of the Kitties from somewhere.
- 19:02So is the heart pumping right
- 19:03or some sort of cardiomyopathy?
- 19:05Or cardio renal?
- 19:05Then it gets out of the heart and
- 19:07it's going down to the orders or
- 19:09some blockages it turns in the
- 19:11renal artery is Adblock.
- 19:12Now it's going into a farneti real.
- 19:14Is that basic constricted urine there
- 19:16in the Kappel Aries in their list is
- 19:18there fibrin plugs are clots there.
- 19:19Is there some sort of PMA?
- 19:21You're going into the target
- 19:22trying to get filters,
- 19:23ovation membrane or their
- 19:24subendothelial deposits.
- 19:25The basement membrane injured
- 19:26other subepithelial deposits.
- 19:27How to produce sites look.
- 19:28Bear in the Bowman space
- 19:29into the tubules of the Tuba.
- 19:31Fielder sells OK.
- 19:32Is interstitial look OK or
- 19:33their casts or blockages?
- 19:34And then you're flying out into
- 19:36their structure on the way out.
- 19:38So fly through the kidney and you
- 19:40won't miss any other costs.
- 19:42How did you come?
- 19:43You zoom in and you go through
- 19:46there. Romario OK,
- 19:50so differential diagnosis to
- 19:54break that down a little bit more
- 19:56if you always walk through it.
- 19:58This way you really never
- 20:00gonna miss any causes,
- 20:01even if they're not what seems likely
- 20:03there or more probably first blush.
- 20:06So the first thing is got through infusion so
- 20:08they aren't the kidney to filter the blood,
- 20:09it has to get the blood.
- 20:11So you look at the different
- 20:13ways that could happen,
- 20:14because just because the kid he's not being
- 20:16perfused does not necessarily mean that
- 20:17the patient's total body volume depletion.
- 20:19So the volume is there is not there.
- 20:21So that's the simplest when you said how
- 20:23many but hemorrhage you are, in fact.
- 20:25Volume is there but in the wrong place.
- 20:29You've increased capillary
- 20:30permeability of sepsis.
- 20:31You third spacing Iorana Sarkic,
- 20:33but you're interested.
- 20:34The bomb is there an senior vascor,
- 20:37but it's not being pumped.
- 20:39You have cardiology cardio,
- 20:40renal syndrome, have tampered on.
- 20:42The volume is there into master.
- 20:45It's getting pumped that's being
- 20:46blocked before you get to the kids,
- 20:49either arenaria thrombosis
- 20:50or more micro bachelors.
- 20:51Something like
- 20:52a battery. Then you move into
- 20:55the small vessels.
- 20:56Then you're going to come in here first.
- 20:58You're a parent,
- 20:59so this is a potentially functional form,
- 21:02something causing a Ferrant vasoconstriction.
- 21:04So N says anything that reduces
- 21:06prostaglandin synthesis,
- 21:07automated contrasts, calcineurin inhibitors.
- 21:09Then in the Kappel Aries himself
- 21:12carefully Brockage Hcpro Globins Bathroom,
- 21:14Bob disease, balloon hypertension.
- 21:16Fear zooming through the basket for her.
- 21:20And now you're coming out to the parents.
- 21:22So this is your classic.
- 21:24Your API CDA isis where you give someone an
- 21:26Acer and R you dilate your urethra material
- 21:29and producer intramedullary pressure,
- 21:30reduce the force pushing
- 21:31across the basement membrane.
- 21:33Reducere filtration fraction.
- 21:33Your crafting goes up.
- 21:35Your Geo fire hose down,
- 21:36which is of course the intended
- 21:38effect of the scenario is not a side
- 21:40effect that is the intended effect,
- 21:42and that is going to show long term in
- 21:44the preservation of that compare list,
- 21:47but short short term like in a bump,
- 21:49small bump in creatinine.
- 21:52So after you move to your basket,
- 21:54reunited across the basement membrane,
- 21:56these aren't pretty pictures as
- 21:58as they've had this morning,
- 22:00but nice little DMS.
- 22:01So are there any stuff into
- 22:03feel deposit strategy?
- 22:04BM or lupus or MPG?
- 22:06And these are just API processes.
- 22:08Everything that you can find in the.
- 22:10Then on the X Ternal you going through
- 22:13the Porter sites and bowmans capsule.
- 22:15Other infectious postinfectious
- 22:16deposits there.
- 22:17So it really.
- 22:18I once you're involved in space,
- 22:20are there Crescent?
- 22:21So how's the immune genes,
- 22:23IGA,
- 22:23lupus or crios?
- 22:25Then moving into the tubular system,
- 22:28are there necrotic replied Tubular cells
- 22:30so this could be from Atn?
- 22:32This could be from taking a property.
- 22:35This could be from bio pastor bile,
- 22:37salts from light chains.
- 22:39Is the two bills blockings itself blocked?
- 22:42So is there a problem with just urine
- 22:45flow after the filtrate informed
- 22:46from cast grand or caster crack
- 22:49cast with my Loma or contrast,
- 22:51which itself imposes sledging and a blockage.
- 22:54And his interstitial inflamed.
- 22:56So is there a end crystals
- 22:58after about disease,
- 22:59or even infiltrated things such as lymphoma,
- 23:02which isn't that common cause
- 23:04they finally collecting system?
- 23:05Once you've made your and you gotta get out,
- 23:09serves that obstruction for any of
- 23:11the common causes, obstruction,
- 23:13or is a functional problem,
- 23:15so is a neurogenic bladder.
- 23:17Medications from a neurologic
- 23:19disease from anticholinergics.
- 23:21And then miscellaneous a few other ones.
- 23:24Renal vein thrombus,
- 23:25which would cause an API.
- 23:26Also proteinuric API or
- 23:28abdominal compartment syndrome.
- 23:32OK, so just because Lloyd started
- 23:34premium went through all this last week.
- 23:38I'm gonna start posting all
- 23:40so there so etiologies.
- 23:42Anything to think of anything?
- 23:44Cause a blockage,
- 23:45so anything in the prostate stones
- 23:48typically have to be bilateral,
- 23:50must have one solid type,
- 23:52functioning kidney, pelvic tumors,
- 23:54or Mets ovarian cancers are big files there.
- 23:57Retroperitoneal fibrosis?
- 23:58Someone history of IgG,
- 23:59four disease or logic as the user.
- 24:02Radiation at learning process and
- 24:04promise anything else.
- 24:06So the diagnosis.
- 24:06So the diagnosis of post
- 24:08renal is almost always made.
- 24:09Our should almost always
- 24:10made with the history,
- 24:12so will show the data on this in a minute,
- 24:14but very rarely does someone
- 24:16coming off the street with a
- 24:18broken leg and you notice the
- 24:20labs that they have API at a loan.
- 24:22Behold was due to obstruction.
- 24:23So this is where you take him to do.
- 24:26They have a history of any of these things.
- 24:29Or do they have symptoms of instruction?
- 24:31Are they having difficulty urinating,
- 24:32having to strain,
- 24:33or forces it saying this year?
- 24:34Is there blood in the yard
- 24:36they having flank pain,
- 24:37but they have a history of
- 24:39something that predispose them?
- 24:40Or do they have symptoms of it now?
- 24:42If they don't have any of those things,
- 24:44it's very unlikely to be postrenal.
- 24:46There are no specific lab findings.
- 24:48Obstruction is one of the settings
- 24:49where you can see the highest
- 24:51creating 'cause this is can develop
- 24:53more insidiously and not in a rapid
- 24:55setting where they have other
- 24:56problems other than obstruction.
- 24:57So this is where you can see it
- 25:00grabbing about 2530, almost even.
- 25:02With obstruction.
- 25:03Importantly,
- 25:03preserved urine output does
- 25:04not rule out obstruction.
- 25:06So I saw a case of this at
- 25:08the VA a little while ago.
- 25:10Unfortunately,
- 25:10case where someone came through the
- 25:12ER with triage in the ER and then
- 25:15discharged without any ultrasound,
- 25:16despite the fact they were saying
- 25:18they're having trouble going and they
- 25:20would notice some pink in the urn at home.
- 25:22But since there are still paying the
- 25:24position so I can't be obstruction 'cause
- 25:27they're still being and they came back,
- 25:29you know,
- 25:30week later,
- 25:30the grad needed 15 and seven or
- 25:32something had to be dialyzed.
- 25:34So just affect someone,
- 25:35so your name does not mean there's
- 25:37not a sufficient instruction
- 25:38that pressure propagating back
- 25:39to cause tubular entry.
- 25:41It's like someone that can have
- 25:42a new impacted fecal less than
- 25:44F diarrhea around it.
- 25:45So you could still obstruction despite
- 25:47the fact you're still urinating.
- 25:51But So the yellow experiences
- 25:54to study now down about 10
- 25:56years ago a cross sectional study where
- 25:58the derivation and validation looking at
- 26:00ultrasounds done for a suspected obstruction.
- 26:03They end up finding 100 patients
- 26:05with hydro and comparing them 100
- 26:07without and then nearly 900 picture
- 26:10800 patients in the validation color.
- 26:12And this is a lot here,
- 26:14but we're just kind of looks important ones.
- 26:16This is just the discovery where they
- 26:19have patients without hydro and one
- 26:21with who had the higher the patients
- 26:23with the history of hydro and previous
- 26:25imaging history of abdominal pelvic cancer,
- 26:27history of recurrent UTI eyes.
- 26:29History of a diagnosis
- 26:31consistent with obstruction.
- 26:32So again the diagnosis is in
- 26:35the history almost certainly.
- 26:38Who didn't have a obstruction?
- 26:39Locations for the history of prerenal
- 26:41or patients who are hypotensive or
- 26:43patients who exposed and effort auctions.
- 26:45Where you'd expect theology
- 26:46might be more of an ATM,
- 26:48so the history is critical in the
- 26:51diagnosis of obstruction in critical in
- 26:53deciding who needs to get an ultrasound.
- 26:55So this is they took those findings in the
- 26:58previous slide though or Sicily sniping it.
- 27:00It made a couple of models and then
- 27:03stratify people in either low,
- 27:04medium or high risk based on
- 27:06the performance of those models.
- 27:08And then look at it with that.
- 27:10How many patients who got ultrasounds
- 27:12ended up having hydro or did not?
- 27:14And as you can see in the low risk
- 27:17extremely small number on depending
- 27:19which model used but still very small
- 27:21ended up having having hydro with a
- 27:23very small negative likelihood ratio.
- 27:25Their prevalence only about 3%
- 27:27in the low risk.
- 27:29That's how to overall higher.
- 27:30This is how to requiring intervention,
- 27:32so sometimes you see a mild
- 27:34hybrid not do anything about it.
- 27:35This is the one you really don't
- 27:37want to miss it here essentially
- 27:39not so one out of 231 out of 345,
- 27:42then their lowest group.
- 27:43Almost certainly they don't have
- 27:44interventional requiring obstruction.
- 27:48Prevalence of less than .5%.
- 27:53And this is
- 27:54just looking at that graphically.
- 27:56Hydro Gen, Lower Skype,
- 27:58requiring intervention into low,
- 27:59medium and high risk groups.
- 28:05So who needs an ultra?
- 28:06Not everyone, so someone comes in
- 28:07with a Ki recalled to consult for
- 28:09someone AKA I do the history first.
- 28:11Now if they come to the ER,
- 28:12it's very possible that guy millstone.
- 28:14Anyway, as we know an approach in the ER.
- 28:16But if they've managed to
- 28:17make it through without that,
- 28:18unless they have one of these either,
- 28:20histories for symptoms you do not
- 28:21need an ultrasound as part of
- 28:23your initial work upgrade behind.
- 28:24You can save a lot of money that way.
- 28:26If you do the usual work up and
- 28:28nothing jumps out after your first
- 28:29free and then sure by all means,
- 28:31then you can move on to it.
- 28:33But it should not be part of the
- 28:35initial work up of everyone with AI.
- 28:40I just some some some reason that study
- 28:42so some people have had postulated.
- 28:44Well now maybe they I,
- 28:45but if we do ultrasounds these
- 28:47people maybe will pick up some some
- 28:48occult carcinoma or some other
- 28:50findings that we wouldn't otherwise.
- 28:51There are no previously unknown.
- 28:53All these hundreds of patients
- 28:54know previously unknown incidental
- 28:55findings and actually in front of
- 28:57probability to study even undersells
- 28:58the extent to which you don't need an
- 29:00ultrasound because these are people
- 29:01who already got the ultrasound.
- 29:03So these are already somewhere
- 29:04someone thought that was indicated.
- 29:05So if you take the whole group API in
- 29:07general you already screwed out of
- 29:09the least likely once those numbers
- 29:10would be even more impressive.
- 29:12He took all comers
- 29:13with API. OK questions on that.
- 29:25OK, moving on to premium also
- 29:27pre raise that email reflects
- 29:29renal hyperperfusion it does not
- 29:30necessarily imply a volume depletion.
- 29:32The treatment therefore does not
- 29:34always imply volume resuscitation.
- 29:35Everyone who is hyperperfusion the
- 29:37kidneys does not need a bullish sailing.
- 29:39Sometimes the volume simply has to be moved.
- 29:45Diagnosis again, history is critical,
- 29:46so similarly to the obstruction,
- 29:48someone who's not just walked off the
- 29:49street and the volume depleted, right?
- 29:51Just 'cause you're rounding as a as a student
- 29:54on words button on Peters for three hours.
- 29:56You don't have AI, right?
- 29:58So do they have some history that would
- 30:00cause or explain about if we should?
- 30:02Have they been sick at home?
- 30:04Vomiting, diarrhea, poor peo intake?
- 30:05And they're not running a marathon?
- 30:07Did you find them wandering?
- 30:09Lost in the desert?
- 30:10There's something in the history that
- 30:12could explain actual long depletion.
- 30:14That doesn't always help in terms of when
- 30:16you have volume that's in the wrong place,
- 30:18so determining intravascular
- 30:19volume status can be difficult.
- 30:21So if someone is an Sr kick,
- 30:22you may not be able to tell whether
- 30:24in Vaseline factor actually drive,
- 30:26but we're talking bout full body volume
- 30:28depletion and diagnosing previewed.
- 30:29All the answers in the history
- 30:31exam the exam can be deceiving
- 30:33'cause you can't look neater,
- 30:34vascular status of the lab test here.
- 30:36I will talk about these more imminent in a
- 30:39bit more detail view in crappy ratio over 20.
- 30:41This is not anything
- 30:42that windows no here but.
- 30:44That ratio is elevated here because
- 30:46you re is gonna be passively reabsorbed
- 30:48along with sodium and water after it's
- 30:50been filtered by approximately urea
- 30:52passively or when your soda when you're
- 30:54prerenal involving completed or hyper
- 30:56fusing your kidney become sodium.
- 30:58Avid reabsorb more that sodium in
- 31:00water and urea comes along with it,
- 31:02so you're viewing rises out of
- 31:04proportion to create any not
- 31:06reflecting and changing GF are,
- 31:07but we're reflecting increased reabsorption.
- 31:09Similarly,
- 31:09when you're producing the kidney and the
- 31:12Kitty perceives that your volume depleted,
- 31:14physiologically sodium equals volume,
- 31:15that's one.
- 31:16How come you could do all that
- 31:17when you seen residents in the war
- 31:1920 great teaching points,
- 31:21sodium equals volume for the body.
- 31:23So if your kidneys being hyper refused,
- 31:25it thinks that your volume depleted.
- 31:26Whether you are.
- 31:27You aren't things that your volume pleated,
- 31:29therefore thinks you're so depleted,
- 31:30and since it wants to help you
- 31:32out and most intelligent organ in
- 31:34the body is going to do that.
- 31:36So sorry,
- 31:37absorbing sodium become more sodium Abbott.
- 31:39And that leads into the FINA.
- 31:41One of our favorite tests.
- 31:43So what is that actual data on the female?
- 31:47So this is the first paper, really.
- 31:50This was described 1976 classic.
- 31:52Earlier,
- 31:52an apology patient paper was
- 31:5417 patients in Newton JAMA.
- 31:55If only we can do that these days.
- 31:58So these 17 patients in order to be
- 32:00at the FINA use and so therefore the
- 32:03actual approved indication for FINA,
- 32:05they had to be all uric.
- 32:07They had enough in any diuretics
- 32:09that have no history of CKD,
- 32:10and they're not had did not
- 32:13receive any Ivy fluids.
- 32:14Is that how it's used today?
- 32:17Of course not.
- 32:18The FINA has metastasized
- 32:19throughout the hospital to use,
- 32:20and everyone with increasing crowding,
- 32:22which doesn't mean it will get to 2nd,
- 32:24doesn't mean you can't use it.
- 32:26In these situations it means
- 32:28you have to keep these in mind,
- 32:30interpreting it, but just know
- 32:31that the official guidelines for an
- 32:33official setting in which it was first
- 32:35discovered was in this very strict,
- 32:37very minimalist patient group.
- 32:40So these are the patients here
- 32:41in this very first study.
- 32:43So firstly you can see these are
- 32:45the crannies is all very serious
- 32:47API translator 9 this was not
- 32:49the patient went from 1 to 1.4,
- 32:51they they waiting pretty long
- 32:53time before ordering.
- 32:54This big difference here between
- 32:56in between prerenal an ATM.
- 32:58I miss you.
- 32:59Just showing something we see
- 33:01clinical practice of why we're using
- 33:03Pena and not just urine, sodium.
- 33:04She said urine,
- 33:05sodium should be low in someone
- 33:07who's prerenal and it is,
- 33:08but there's significant overlap here.
- 33:10So this test urine,
- 33:11sodium looking at their pre
- 33:13rotations through ATM.
- 33:14These are getting very severe
- 33:1518 patients and they still have
- 33:17low urine sodium and in many
- 33:18cases whereas Athena very nicely
- 33:20distinguish the two.
- 33:21So this gives you published
- 33:23in JAMA with your 17
- 33:24patients. How about in CKD? So
- 33:27this is one of the things that I think
- 33:29people don't don't think through very often,
- 33:32but it's important thing to realize is
- 33:34you kind of take this under the floors.
- 33:36Seeking patients were excluded
- 33:38from that personal study,
- 33:39and for many of the equally small
- 33:41evaluation papers in the late 70s,
- 33:43can we use it in seeking
- 33:45to answer that question?
- 33:46We need to take a little detour here
- 33:49and look at at Geo far and cracking the
- 33:52relationship between the two of us.
- 33:54And this is using.
- 33:55I know them that scratching his debts
- 33:57later using before someone in chat rooms
- 34:00were using MLS here for math reasons.
- 34:02So looking at someone in the steady state,
- 34:04so if we're on the wards and we
- 34:06give you just take em setting.
- 34:09Know demographics,
- 34:09no patient information,
- 34:10no nothing,
- 34:11just account 7 and ask you to roughly
- 34:13rough estimate the Geo far right.
- 34:15You'll tell us that it is roughly.
- 34:20Never do that. Just no, no. Security
- 34:27happy formulas no MBR dies,
- 34:29just that comes out.
- 34:32New Cockroft Gault.
- 34:34We don't have age.
- 34:36Crash right one over the credit roughly,
- 34:38and This is why that is.
- 34:40And this has some relevance,
- 34:42so normally you are in a steady state.
- 34:44Your GF arcea 100 milliliters minute,
- 34:45if one milligram per I know,
- 34:47milliliter of blood here,
- 34:49which means you're clearing
- 34:50100 milligrams of it.
- 34:51Your company is at 0, however,
- 34:53because you're also producing under
- 34:55demanding producing 100 or clearing 100 year
- 34:58in a steady state you're cracking is 1.
- 35:00If your GF are drops if your
- 35:02Sheriff RS50 now you're filtering 50
- 35:04milliliters minute initially a crap.
- 35:06You still 1 milligram per milliliter,
- 35:08and so you're clearing 50
- 35:10milligrams a minute.
- 35:12However, because you develop CK,
- 35:13you haven't changed a crafting productions,
- 35:15so you're still making 100 a minute.
- 35:17You're not only clearing 50 minutes,
- 35:18so you're going to positive balance.
- 35:20You're making more than your clearance.
- 35:21Recreating starts to rise,
- 35:23and it's going to rise and
- 35:25rise until it gets to two.
- 35:27So now you're still filtering
- 35:2850 milliliters a minute.
- 35:29But now with two milligrams per milliliter?
- 35:31So clearing now once again
- 35:33100 milligrams per minute.
- 35:34You're making 100.
- 35:35You're clearing 100 back in steady state.
- 35:37However,
- 35:38the cost of a crafting going up to two.
- 35:41And that continues on down the line here.
- 35:44Such that all way down,
- 35:46if you're crafting your GF are drops
- 35:4820 mcraney rising so it's five.
- 35:50Once again you're making 100 or clearing 100,
- 35:52but at the cost of grounding rods after five.
- 35:55So two things to take away from this one
- 35:57is is the difference in the change in
- 35:59GFR for any given change in creating?
- 36:02This goes back to why we care about small
- 36:04changes that branding and diagnosing API.
- 36:06So to go from four to five here is only a
- 36:09change of five in your GFI from 25 to 20.
- 36:12Very little if you go from grinding.
- 36:14You'll get a call sometime.
- 36:16Someone who had monitoring just
- 36:18kind of watching the granting
- 36:19float around in the floor.
- 36:21Since going from 8:00 tonight and panic
- 36:23in the streets, there's nothing at all.
- 36:25No change.
- 36:26Volunteer Fire.
- 36:27Everyone wanted 2 the same absolute change.
- 36:29You lose 50.
- 36:30Miller should have far,
- 36:31and in fact we go from 1 to 1.3.
- 36:34You go from G FR100G apart 75.
- 36:36So go from 1 to 1.3 lost
- 36:381/4 of your Geo part,
- 36:4025 milliliters in it which
- 36:41by very small changes.
- 36:43Especially when started someone
- 36:44starting a low baseline.
- 36:45Are actually indicative of very
- 36:47large changes in GF are and why we
- 36:49actually think that these very small
- 36:51changes in terms of diagnosing API
- 36:53plausibly has physiologically significance.
- 36:55OK, so hold that thought
- 36:57here very roughly,
- 36:59so went back to to FINA and see KD.
- 37:02So let's say your baseline kragnes three,
- 37:05which means your GF are roughly rough.
- 37:08103 is about 30 three so you have CK di.
- 37:12Normally when your GF eyes 100 you're
- 37:14building 100 milliliters a minute.
- 37:16You're sodium is under 40 millivolts amended,
- 37:18and your normal feet is about
- 37:20one your excreting 1% of your
- 37:22filters Williams every minute.
- 37:23You're extremely about .14
- 37:25milliliters minute of sodium,
- 37:26and this is what you need in order
- 37:28to stay in sodium balance and the
- 37:31Kitty prioritizes volume down,
- 37:32so the kidney,
- 37:33as you've seen from all these
- 37:35wonderful lectures over the summer,
- 37:37is all sorts of fantastic things
- 37:39with electrolytes and acid base.
- 37:40But sometimes the different functions
- 37:42that can be common conflict.
- 37:44And no matter how much you titrate up,
- 37:46regulate your different way.
- 37:47Kinases in such things, sometimes.
- 37:49Changes that are going to maintain
- 37:50volume balance are going to be
- 37:52disadvantageous for maintaining
- 37:53electrolyte or acid base balance,
- 37:55and sometimes the kidney has to
- 37:56prioritize and Prioritizes Volume balance.
- 37:58And since volume equals sodium,
- 37:59you can think of the kidneys prime
- 38:01directive is in maintaining sodium balance.
- 38:03That is what is better prioritize if
- 38:05it that means it has to mess up your
- 38:07chem 7 so it looks awful and epic.
- 38:10It will do so,
- 38:11so you want to maintain Sony bouts.
- 38:13In order to do so,
- 38:14you need to get rid about .1
- 38:16four milliters minimalism.
- 38:17These are rough made up numbers.
- 38:20They develop cecati in your GF are
- 38:22drops at 33 in your nephrologist house,
- 38:24so you have to reduce your sodium intake
- 38:26because you're filtering less blood.
- 38:28If you start excreting less sodium but
- 38:30you're still taking in the same amount,
- 38:32you're going to have a positive
- 38:33sodium balance.
- 38:34You're going to positive volume
- 38:35balance and you develop hypertension,
- 38:37which is why these patients
- 38:38as each progressive CD almost
- 38:39universally develop hypertension.
- 38:40Despite telling your patient
- 38:41to reduce their sodium intake.
- 38:43In fact, they.
- 38:45Often doritis or sodium intake,
- 38:47so they're taking the same on
- 38:49sodium as they were before.
- 38:51Everything said equal in
- 38:52their GF far is now 33.
- 38:53It's a third of what it was.
- 38:55Their serum sodium concentration
- 38:56hasn't changed their penis to 1%.
- 38:58So now there are links creating
- 38:59a third as much as they were
- 39:01before they change their building.
- 39:03A third as much blood with the same
- 39:05sodium concentration in the blood.
- 39:06Therefore they're excreting a third.
- 39:08As much sodium is over before over
- 39:10there taking in the same amount.
- 39:11So if they're taking the same amount
- 39:13but only excreting and 3rd as much,
- 39:15they're going to positive sodium balance,
- 39:17so they need to start excreting more
- 39:18sodium in order to stay stay sodium neutral.
- 39:21So if they only filter 3rd as
- 39:22much as they did before,
- 39:24but they need to excrete the same amount.
- 39:27Instead of extruding 1% of the filter though,
- 39:29they need to excrete.
- 39:31What percent?
- 39:39Three day yes, very good.
- 39:40It's not not trick math,
- 39:42so you're filtering only a third as much,
- 39:44but you need to excrete the same amount,
- 39:47so previously exceeding 1% got to the
- 39:48required amount of sodium excretion.
- 39:50Now we need to treat 3%,
- 39:52but it's only 1/3 as much,
- 39:54so that's being filtered in the first place.
- 39:57So, roughly speaking,
- 39:58roughly speaking, when you have sikidy,
- 40:00your FINA should be roughly about
- 40:02what you're creating is now.
- 40:03The thing with chronic kidney diseases,
- 40:05that means your kidneys have disease,
- 40:07so this doesn't work perfectly.
- 40:09This is by no means precise,
- 40:11but roughly speaking,
- 40:12if someone is baseline premise
- 40:14three and they come in at 7:00,
- 40:16if you check their FINA and
- 40:18it's a 2.5 close enough right?
- 40:20It's not that precise,
- 40:21but if it's 1.2 right normally, haha.
- 40:241.2 that's above 1 this this can't be prove,
- 40:27you know.
- 40:27For this given patient that is quite well,
- 40:30so you can determine you can
- 40:31use feed in setting of CKD,
- 40:33but you have to reconceptualize what
- 40:34the normal should be for that patient
- 40:36given their baseline in the back there.
- 40:38Trying to maintain sodium balance
- 40:39with a lower net amount of
- 40:41overall sodium filtration.
- 40:45That makes sense. OK bye cross fingers. So
- 40:48generally speaking not too much. Macy
- 40:50Highland castmates each other Theo sales
- 40:52in Rhode Island cats or your Tam or so
- 40:56proteins which are the backbone of all
- 40:58your casts that red so cast is red so
- 41:00stuck on commercial proteins so we have
- 41:03preview in your urine flow is sluggish,
- 41:05transvestite the clump together in forecast.
- 41:07That's why you see that.
- 41:10I will bring your casts.
- 41:13How can we see granular casts
- 41:15in premium doesn't isn't that
- 41:17indicative of tubular entry?
- 41:19Mobile that reduction in
- 41:22Jeep parts. It's not the
- 41:25same everywhere,
- 41:26so depending on where you're at,
- 41:29proximal tubule is hypoxic.
- 41:30It is begin with.
- 41:32You can have actual ATM. Yes.
- 41:37So here's your kidding.
- 41:38So you have a million
- 41:39nephrons in your kidding.
- 41:40But they're all not equal, right?
- 41:42This Is This? Is there up in the
- 41:44cortex or juxtamedullary there
- 41:45somewhere closer to that picture,
- 41:47somewhere further from Mass, which
- 41:48are an just like the animals in the farm,
- 41:51you know all that bronze vehicles.
- 41:52But some are more equal than others.
- 41:54Some are more vulnerable than
- 41:55other side Perfusion. So yeah,
- 41:57some of them are up here in your cortex,
- 42:01summer down in your medela.
- 42:03So if one is really slowly turning.
- 42:07There are not going to be a confused with
- 42:09the same aggression in the same time frame.
- 42:12So if you have some there particularly
- 42:14vulnerable and you're hyper confused
- 42:16that patient for a little bit,
- 42:17you may indeed have death of those
- 42:19bigger cells in those networks,
- 42:21and those supercells may Slough off and
- 42:22go into the tubule lumen and sit there
- 42:25long enough such that they degrade and
- 42:27the dead broken down granular debris
- 42:28of those slots too liberal cells is
- 42:30the granular debris that forms,
- 42:32are granular casts,
- 42:33and if you look in the urine at that patient.
- 42:36There you go, right?
- 42:37You're going to have the granular cast
- 42:40come out from those that tubular cells,
- 42:42and you might think I had this patient is 18.
- 42:45However,
- 42:45if that is only say,
- 42:475% of the patients nephrons,
- 42:49if you give them volume,
- 42:5095% of nephrons are structurally intact,
- 42:52they're going to respond to the re perfusion,
- 42:55and your cat is going to come back down.
- 42:58You're going to call this patient Prerenal,
- 43:00and that is the critical point.
- 43:02I think looking mother Rene's
- 43:03discussion of the mechanisms and
- 43:05diagnostic criteria behind criminal.
- 43:06But Really,
- 43:07you can't actually fully make the diagnosis
- 43:09of Prerenal before giving the volume
- 43:11challenge that they really cynical,
- 43:13known of the definition of Prerenal,
- 43:15is responsible matter what
- 43:16you think should happen,
- 43:18what their history was,
- 43:19what the presentation was.
- 43:20If you adequately restore renal perfusion,
- 43:22which is key,
- 43:23you may not have given up volume,
- 43:26maybe third spacing.
- 43:27If you added lira store Reno Perfusion
- 43:29and their cracking comes down Rapids
- 43:31their baseline, they had premium.
- 43:33If they don't, they don't.
- 43:34Regardless of what is happening
- 43:36structurally in there,
- 43:37how much damage is in the pupils?
- 43:39Responsive fluid is the definition
- 43:41that hallmark definition of
- 43:42provisional premium is not.
- 43:44A disease is a physiologic state and is
- 43:46defined by physiologic response to treatment.
- 43:48It cannot be defended,
- 43:49it could be very,
- 43:51very suspicious,
- 43:51but it cannot be definitively distinguish
- 43:53meitian probably volume trial,
- 43:55because you could have evidence of
- 43:57structure entry on both in Europe
- 43:59because it is a spectrum in between.
- 44:01What tips you from calling this person,
- 44:03for you know with 21% of nephrons damage
- 44:06and this one ATM with 26 percent is
- 44:09whether they respond to volume or not.
- 44:11Questions on that.
- 44:17So ATM, so the three kind
- 44:20of hallmark etiologies,
- 44:21beach and ischemic that Frittata accepted
- 44:23until time to talk much about this.
- 44:25But this is kind of really
- 44:28exciting for other people.
- 44:29Now this is not septic in there
- 44:32setting up hypotension ischaemia,
- 44:33this is normal Tensive ATMs.
- 44:35This is direct to builder in direct
- 44:37route activity from cytokines.
- 44:39This is microvascular disease.
- 44:41Setting up either infectious or
- 44:44noninfectious related sepsis that is really
- 44:46a third distinct ideology outside of
- 44:49ischaemia nephrotoxins So diagnosing atn,
- 44:51so history again this is one of the ones you,
- 44:54the chart, looking for all the
- 44:55exposures at the primaries.
- 44:57You missed microscopy FINA biomarkers.
- 44:58I'm very, very quickly at the end,
- 45:00but we're not going to have
- 45:02much time discussed today.
- 45:03Struggles is not watching this,
- 45:05so I can do that without being castigated.
- 45:07So what do we see in the urine?
- 45:09So these are your two epithelial cells.
- 45:12This is your classic kind
- 45:13of Sunnyside up egg here.
- 45:14If you're really lucky,
- 45:16you could even see a cast of these early
- 45:18on in the setting of API before they.
- 45:21Raid. Like that? It's lovely.
- 45:25Here's your classic granular casts,
- 45:27so market paper.
- 45:28I'll show in a minute.
- 45:30Mark Paradela others to study showing
- 45:32that the number of casts in the urine is
- 45:36indeed predictive of the diagnosis of atn,
- 45:38and outcomes the character
- 45:40appearance of the cast is not.
- 45:42Some of these are very light Brown.
- 45:45Somebody's really dark money Brown.
- 45:47There's no pathologic significance,
- 45:48so that the actual appearance of the casts.
- 45:52So this is now over 10 years ago.
- 45:55This is actually some data from
- 45:57this was as part of a Fellows
- 45:59Performance Improvement Project,
- 46:00which might actually be a good time
- 46:02to stop and mention that I'm still
- 46:04waiting to hear back from the email that
- 46:07spells performance improvement projects.
- 46:09Put on notice.
- 46:11So looking at the yard,
- 46:14looking patients with a Ki am
- 46:16looking not just RTS and Casper
- 46:19quantitating them 01 to five or more.
- 46:22I'm in developing a score.
- 46:24I'm looking at the light leading
- 46:26likelihood ratios to look at based
- 46:28on the number of granular casts are
- 46:30T cells diagnosis of Prerenal an atn,
- 46:32and then the likelihood ratio so you
- 46:35can see here as you go up numerically,
- 46:37the number of casts increase.
- 46:39The likelihood of being ADN decreases.
- 46:41Like could be Greenall Periodic
- 46:43an infinite likely,
- 46:44which is always a good one to have.
- 46:46Same with RT stuff.
- 46:51And then looking at again using these,
- 46:53combining the two of these into a score.
- 46:55Looking at the odds ratio of
- 46:57having ATM based on your score,
- 46:59if you're over two with their score,
- 47:01a massive odds ratio having agency,
- 47:03this is impact.
- 47:04Lotto cash it is predictable.
- 47:09So it looks like that.
- 47:11Then it's gonna be it.
- 47:12Yet when it's a fewer number,
- 47:14then you have to do the volume challenge.
- 47:15'cause whether they respond about
- 47:16how they behave is what gives
- 47:18him the diagnosis, not necessary.
- 47:19What they have histologically,
- 47:20'cause there is overlap.
- 47:22OK, so how about FINA
- 47:23with ATM? So Lloyd mentioned this also,
- 47:25but will go through the math a little
- 47:28bit here so the female with a tan
- 47:30is typically 2 to 3%. Why is that?
- 47:34Quest. The two kids are injured.
- 47:38The cameras are saltwater spills
- 47:40in the air, right? So you have.
- 47:42So you have an elevated feed because
- 47:44all those those two bills and all those
- 47:47transporters that doctor asgar inductors
- 47:49and went through can't function.
- 47:50You can't reserve the Saudis fill
- 47:53it in the air in your Phoenix album.
- 47:56Two energy limits, ability to reabsorb,
- 47:58so he also limits ability reserve water.
- 48:01Why is that? What is false?
- 48:04Also, we had this as one of
- 48:06the questions in Jeopardy.
- 48:07Where is the majority of glow of the groups
- 48:10or in the kidney and other than magnesium?
- 48:13Brola is 2/3 in approximately and that's
- 48:152/3 of sodium with energy 3 and then all
- 48:17the other Co transporters with glucose,
- 48:19amino acids and Phosphate
- 48:20and everything else.
- 48:21And water goes with it.
- 48:23And you have aquaporin channels
- 48:24there that are constituently there
- 48:26he's not responding to Ath there
- 48:28always there always open and so is.
- 48:30Sodium gets reabsorbed,
- 48:31your interstitial modularity
- 48:31goes up a little bit,
- 48:33and waterfalls along with it.
- 48:35So if you have a TN approximately learn tree,
- 48:37you can't reserve that sodium and
- 48:39therefore you can't make that automotive
- 48:41gradient and you don't re absorb water,
- 48:43so you lose both saltwater so.
- 48:45What are the more different Volvo?
- 48:48The less sodium and water
- 48:50that you can be absorbed?
- 48:52And so the more extensive the atn,
- 48:55the higher the urine output.
- 49:02No. What I remember being asked this
- 49:05as a resident, someone asked me this
- 49:07and this I can almost pinpoint this
- 49:09one moment as I really thought this.
- 49:11I'm definitely going to probably
- 49:12since patient with ATM.
- 49:13Why are they all uric right there?
- 49:15Who Mary this is intact
- 49:17there still filtering?
- 49:18There are two bills are injured which
- 49:19would mean they should have polyurea.
- 49:21And I'm not talking about the post.
- 49:23Atn recovery based about weather in the grip,
- 49:25right? Why is someone Atn Stop Peeing?
- 49:28Mining, paradoxically,
- 49:29they should be being more.
- 49:32I and soaps.
- 49:33So the answer may be completely here.
- 49:37There's 2 two kind of mechanical reasons,
- 49:401/5 fun Physiology,
- 49:41beating reason and I meant to animate this,
- 49:45but.
- 49:45So the one reason that she's
- 49:47blocking here is obstruction.
- 49:48So when you have a 10,
- 49:50you have these granular caching debris.
- 49:52You can actually plug the
- 49:54tubules and you don't have you.
- 49:56Make filtrate doesn't get out,
- 49:57two is based on the tooth loss phenomenon,
- 50:00which is that when you have drop
- 50:01out of your stupid feeler cells you
- 50:04have these gaps form your junctional
- 50:06integrity and some of the filter
- 50:08that you make and then back to fuse
- 50:10out so you are making filtrate but
- 50:12it's leaking back in the two bills
- 50:14and being reabsorbed from the.
- 50:167th grade now.
- 50:20OK, So what do you wanna do about this?
- 50:24Well we have to do something
- 50:26because otherwise we would be dying.
- 50:29So as Lloyd said,
- 50:30your normal kidney on a daily basis
- 50:33filters about 180 liters of filtrate blood.
- 50:36I'm sorry which is incredible
- 50:38person right there,
- 50:39so just respect for getting 180 liters today.
- 50:43100 liters with the sodium concentration 140,
- 50:46which means you're filtering 25,000
- 50:48Milla moles of sodium a day.
- 50:51And you say how much?
- 50:53How much milligrams?
- 50:54In a millimole sodium is a mild
- 50:56valent cation trying to remember all
- 50:58the God rose number or something?
- 51:00So they were milligrams for Billable.
- 51:02And sodium is the molecular weight of
- 51:05sodium because it's plus one that's 23.
- 51:07So minimal sound 23 gives you
- 51:09this many milligrams powder.
- 51:1080 grams about 1.3 pounds of sodium.
- 51:12Your filtering pounds of sodium,
- 51:14massive amount of sodium,
- 51:15and if you add ATM in your
- 51:18FINA wasn't actually 2 or 3%,
- 51:20but through his fifteen 2040%.
- 51:21Very quickly you would die.
- 51:23You would be yourself to death from
- 51:26hypovolemic shock. Alright, so.
- 51:30Death from a Tia.
- 51:31Now thankfully,
- 51:31everyone gets ATM doesn't die and the
- 51:33reason for that is the third reason
- 51:35that you're in after drops other,
- 51:37those two mechanical ones.
- 51:39And then it's 2 blueberry feedback,
- 51:41so it probably actually chloride.
- 51:42But people always said sodium,
- 51:44and it's easy to think sodium,
- 51:46but realize it's probably
- 51:47actually write it censored,
- 51:48the macula densa whose job is really
- 51:51to maintain constant amount of renal
- 51:53perfusion regardless of blood,
- 51:54flowed wireless.
- 51:55We know profusion,
- 51:55and so they front aerial is going
- 51:57to modulate the renal blood flow
- 51:59based on the sodium chloride that is
- 52:02coming downstream and have too much
- 52:04sodium chloride gets the macula densa,
- 52:06it says right, where filtering too much.
- 52:08We need to construct a fan arterial.
- 52:10If you have a TNN bluely knockout,
- 52:12your resorption capacity,
- 52:13your proximal tubule, and this title wave
- 52:15of sodium chloride gets the Mcaden set.
- 52:18It says, yeah,
- 52:18and completely clamps off refinanced irial,
- 52:20and then basically goes senescent.
- 52:22So even though the Camaros isn't damage,
- 52:24there's nothing wrong with it.
- 52:25It still capable of filtering.
- 52:27It's not.
- 52:27It is turning itself off in order to
- 52:30save you from being yourself to death,
- 52:32and the more severe diffuse your ATM,
- 52:34the more nephrons are involved in more
- 52:36nephrons are turning themselves off.
- 52:38And that is why the more severe your atn is.
- 52:41Not the Morgan, just for
- 52:43the last year. Yeah.
- 52:46So everyone is asleep except for.
- 52:53Uh. Everybody or everybody you
- 52:55know he was in discuss with the
- 52:59person and identity everyone is.
- 53:02I'm not sure who's talking, but
- 53:06we can hear you. You did them.
- 53:10Leave it unknown who suck
- 53:13it alright so it's just
- 53:16really real failure. No,
- 53:17this is a real success, right?
- 53:20So then I thought this was Lloyd
- 53:22started last year, directed movies.
- 53:24I heard it from first I love it sectors
- 53:27as seen corrected the last year.
- 53:29I've actually comes from paper
- 53:31back in the 70s from John Boylan,
- 53:34acute renal success,
- 53:35beautiful paper at three or four pages.
- 53:37Great to look at.
- 53:39Looking at this in animal models,
- 53:41single nephrons, increasing infusing
- 53:42sodium chloride to the macula.
- 53:44Densa watching the aprons.
- 53:45Stop being atn in order to
- 53:47save yourself from being.
- 53:51So that's great and you see the
- 53:54patient on the Warsan you you
- 53:56write this write this in your note.
- 53:58It's really impressive.
- 53:59It sounds glorious.
- 54:00You're exposing Physiology.
- 54:01Everyone loves the Renal Fellows.
- 54:03the IP Fellows are just saying what
- 54:06antibiotic to use is so boring.
- 54:08You have all this beautiful Physiology
- 54:10your intellectual powerhouses,
- 54:11the hospital their residents are reading
- 54:13the notary interns like Oh my gosh,
- 54:15I want to be apologists eagerly looking
- 54:17forward to your recommendations to
- 54:19cure this physiological horror.
- 54:21And then you say,
- 54:22minimize nephrotoxins And optimize
- 54:24volume sets as though they were
- 54:26going to maximizing effort options.
- 54:28If you hadn't told them that
- 54:30it's embarrassing.
- 54:31This isn't true in animals though,
- 54:34and animals you can do things right.
- 54:36You can give harming whatever that is.
- 54:39If it's beneficial you can give.
- 54:42Extracts you can give garlic.
- 54:44This is from about three months of a
- 54:48pub Med search. Vitamin E, vitamin D.
- 54:51Keep giving stuff all sort
- 54:53of everything works.
- 54:54It says a tremendous number of
- 54:57things which either ameliorate or
- 54:59prevents atn and animal models.
- 55:01Bilberry extracts.
- 55:03This is just a few months milk fat globules.
- 55:09Then we get to the humans.
- 55:11Right and it doesn't work.
- 55:13So statins no. Ipoh, No.
- 55:18Next, definitely no.
- 55:20Steroids no, the question is why?
- 55:24Why is everything working
- 55:25out and not everything?
- 55:26Of course.
- 55:27Why are there so many treatments
- 55:29that seem to be affected?
- 55:31Animals and art in humans?
- 55:33And there's there's two reasons,
- 55:35and we got to finish with this, which is OK.
- 55:37It's not time to go this stuff.
- 55:39One is really the timing right?
- 55:41So the problem with creating is a
- 55:43filtration markers that it's delayed,
- 55:45right?
- 55:45So if we went and if someone
- 55:47fell asleep not then possibly
- 55:48would help during this talk,
- 55:50but if we wanted to get really aggressively
- 55:52punitive and he said, you know,
- 55:54you fell asleep during Reno rounds.
- 55:56We don't tolerate that.
- 55:57Yeah,
- 55:57we're going to cut you open and you know,
- 56:00clap your renewal rate with fires.
- 56:01This is like Maná fewer in the 50s.
- 56:04This is.
- 56:04Cough medicine and their families one right.
- 56:07You know what is your grounding tomorrow?
- 56:11Andrew library little muscle mass
- 56:16is 1.2. So so far it's not.
- 56:20It's not going to be 10.
- 56:21I mean because you're you're in a steady
- 56:23state because you're producing the same
- 56:25amount as your excreting in a matter.
- 56:27What happens, you're excretion.
- 56:28Your production is not going to say the same.
- 56:31Putting inside ICU stuff,
- 56:32so your credit can only go up a certain
- 56:35amount maximally based on how much
- 56:36are producing and when you have 18,
- 56:38even severe atn,
- 56:39it's nearly not complete cessation of GF.
- 56:41Are your credit is going to 1,
- 56:43three, 1.7 to 2 to 2.4 and
- 56:45Reno's gonna get insulted.
- 56:46But the problem is that the
- 56:48injury was four days ago.
- 56:49Alright,
- 56:49so this is coming to your your
- 56:51your cardiology patients had MI
- 56:53and four days after my giving
- 56:55them your 2B3 inhibitors in your
- 56:57Plavix and everything and nothing
- 56:58would work and they rent their
- 57:00garments and say none of these.
- 57:02We don't have any effective
- 57:03therapies for M eyes in animals.
- 57:05You know exactly when the
- 57:07install is happening right?
- 57:08And you can time it the
- 57:10treatment immediately.
- 57:10The 2nd is a heterogeneity so ATM
- 57:13just like Prerenal isn't a disease
- 57:14ATM is not a disease either.
- 57:16ATM is a histologic endpoint.
- 57:18The dead tubular cells with the endpoints
- 57:20of many different pathologic Cascades.
- 57:21You can imagine if your cells dying
- 57:23from ischaemia versus cytokinin,
- 57:25sepsis versus nephro toxicity and cisplatin.
- 57:27The actual pathways and interleukins
- 57:29and totally perceptors everything
- 57:30it takes to get there is extremely
- 57:33heterogeneous and you have one
- 57:34medication to try to treat that it's
- 57:36almost certainly not going to work.
- 57:38Trying to treat chest pain with
- 57:40the drug that chest pain from MI,
- 57:43to massage spasm from rip fracture
- 57:45from zoster from everything else.
- 57:46Give that zoster patient Plavix
- 57:48you're not going to see anything
- 57:50all chest pain together if you want.
- 57:52All. ATM together and give one drug.
- 57:55It's extremely likely you're trying to
- 57:57treat multiple conditions with one drive,
- 57:59where is an animal model.
- 58:00Again,
- 58:00you know the mechanism of a tenure inducing,
- 58:02and you could tell your treatment for that.
- 58:05So we really need is a rapidly detectable
- 58:07in physiologically specific tests.
- 58:08And we used to have a lot of
- 58:10emphasis on biomarkers in this talk,
- 58:13which I left it to do as well.
- 58:15We don't really have time for that.
- 58:17You probably are aware of
- 58:19the renal biomarkers.
- 58:20Hope yes.
- 58:20Not, not if you're not so yeah,
- 58:23you better be,
- 58:24but you send gal is the most prominent one,
- 58:27but their menu there's
- 58:29upwards of 30 now of markets.
- 58:30Generally speaking,
- 58:31these are things that are released
- 58:33to the actual tubular injuries.
- 58:35These are like trip onen myocytes.
- 58:37These are things leaking out of damage cells,
- 58:39so they should rise more rapidly than
- 58:41crabbing and see Rice specific to injury
- 58:44rather than the type of Profusion.
- 58:46This was incredibly,
- 58:47the still is very exciting.
- 58:48This was a lot more exciting,
- 58:50perhaps 10 or 15 years was first coming out.
- 58:53As with many new tests,
- 58:55it's been difficult to operationalize this,
- 58:56unfortunately.
- 58:57US monies are really available to,
- 58:58except for the network check,
- 59:00which is the the temp 1 Ellis LL.
- 59:03ID FD71, which is looking for
- 59:04a cell cycle arrest markers,
- 59:06is a little different and that was
- 59:08supposed to be approved for clinical
- 59:10use this summer that has been delayed
- 59:12with Covid and the company is going
- 59:14to bit radio silence on their
- 59:16data so it's a little concerning,
- 59:18but hopefully I'll be available soon
- 59:20in the US and then we would put that
- 59:23to use and then I was going to go
- 59:25into a again but I think I'll save
- 59:28that interest in time for desk.
- 59:30Who's giving a in top? So.
- 59:33That's it.
- 59:35Questions.
- 59:42Thank you doctor Belcher. OK,
- 59:46no that's good, thank you. Thank you.