NC 2020.08.14 Dr Asghar Renal Tubular Acidosis

October 16, 2020

NC 2020.08.14

Dr Asghar Renal tubular acidosis

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00:00Yes, I thank you very much for inviting me,
00:03so we're going to talk about. Tess.
00:07You may dispense initially with some of the.
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00:17Uh. There's no commercial support.
00:21This is the number you need to use.
00:25To get CME credit for this conference.
00:29August 14 conference I have no disclosure.
00:34So what I'm going to talk about initially
00:38is hyperchloremic metabolic acidosis or
00:40non anion gap metabolic acidosis were
00:43the problem is not in gay Navarre said,
00:47but in loss of base.
00:50Then I will talk about what
00:52we know about genetics,
00:54Amartya or theory is fairly rare.
00:57Disorder.
00:58But it actually shows a great deal of
01:01light or normal Physiology of acid base
01:04regulation by the kidney appear to give
01:07a wonderful talk a couple of weeks ago.
01:10This will, you know,
01:11sounds komplement summer thing that he said.
01:14Then I will move on,
01:16talk about the clinical, presentation,
01:18diagnosis and treatment all or here.
01:21No, the patient presentation is
01:24initially with an acidosis iir,
01:27low bicarbonate by high chloride,
01:30no one on ion, and the issue is,
01:34is it due to GI loss of bicarbonate diarrhea?
01:40Or is the arena origin were the problem?
01:43Is either loss of bicarbonate by the kidney?
01:47Or there's a defect in
01:50generational bicarbonate.
01:51By the kidney.
01:53To just remind you about Peter talked about,
01:57we have to initially reclaim about 5000
02:00milligrams of back hornaday any loss
02:02of bicarbonate is additional asset
02:04to the body disapper i'ma leave the
02:07job that's done by proximal tubule
02:10were shooting hydrogen exchanger,
02:12allows the back order to recover
02:14or two just point out there is
02:17carbon hydrates in the brush border,
02:20data type floor and one in the
02:23cytoplasm that allows it to be.
02:26A bulk removal of bicarbonate
02:2885% happens in proximate trivial.
02:31There's an exit pathway through
02:33electrogenic sodium carbonate bicarbonate
02:35exit lot and come back to that.
02:38So rest of reclamation occurs in loop
02:41of Henle again through the sodium
02:44hydrogen exchanger sorted by time
02:47you get to a core collecting duct.
02:50Most of the back corner of this
02:53all has been reabsorbed.
02:56Under job,
02:56here is a different job is really
02:59to regenerate about corner lossed
03:01in neutralization acid that has been
03:04part of your dietary intake is only
03:07about $70,000,000 a day in assembly,
03:10kilogram, individual.
03:10But it can add up over period of time.
03:14So every day we need to regenerate
03:1770 million colon, we do that.
03:20Partly by Tuttle acid phosphate
03:22within the major part of it,
03:25but much of it also by ammonium me.
03:28Look at that lipid more in detail
03:31because that's where.
03:33This becomes complicated if you
03:35look at this a convoluted tubule.
03:37Sorry acorda collecting duct,
03:39you have three different cells.
03:41One is the principle cell within
03:44ACH and Ron K.
03:45This is primarily to create the
03:48negative charge in the tribute.
03:50At the same time they absorb sodium in
03:53exchange for execution of potassium.
03:56As also the cell that has a
03:59koporin allowing water
04:00they absorption.
04:02Then there are intercalated cell type.
04:04A were showed him hydrogen exchanger
04:06is an aluminum side and the unknown
04:09exchanger dialogues chloride bicarb
04:11and exchange on the base for last.
04:14For this could be switched over
04:16with none in exchange or which is a
04:20different molecule called pandering
04:21on the Lumenal side and how to
04:24germinate EPS on the blood side.
04:27Remember that here we have
04:29correct on high risk type 2.
04:32That is important in the cytoplasm.
04:35Allow this reaction to go.
04:37Turn it about coordinate to
04:40move hydrogen to be secreted,
04:42or the opposite with academic secreted
04:45sorptive than it is to deliver Columbia.
04:51Now to make sure. A.
04:54Molecule in the major buffer.
04:56The past allows us to actually respond to.
05:01Acid loading or respond to the
05:03acid I beat in a day is not taxable
05:06asset that only changes mildly
05:09depends on the phosphate intake.
05:11It really is primarily armonia
05:13iamonia excretion can go up
05:16tenfold from 40 milligrams a day,
05:18which is normal to 400 mill class.
05:21It doesn't have to do that again to
05:24remind you what Peter described in detail.
05:27Is that ammonium ion is actually
05:30generated in proximate, trivial.
05:32As NH 4 plus,
05:34this comes from the glutamine
05:36molecule going through a fairly
05:38complex cellular reaction.
05:40If it's true, different pathways,
05:42but and you end up with ammonium ion being
05:46generated in the Approximate Tribune,
05:49there is a sharp pathway in the
05:51loop of Henle so that ammonia
05:54could replace potassium and then
05:57be changed to ammonium gas,
05:59which is then secreted into the.
06:02Collecting dark with hydrogen now
06:04coming out of intercalated cell,
06:07making ammonium ion,
06:08trapping it and out of the ammonium.
06:11That's made here about 100% of
06:13what comes out of here is it is
06:16coming on approximate reviewer.
06:18There is a limit of absorption
06:21ammonia back to the circulation.
06:23Any ammonia that goes back to
06:25circulation it could be 20 percent.
06:2840% of that will then react
06:31with the bicarbonate generated.
06:32Influx or trivial to make urea molecule
06:35so internal net total body event.
06:38It really is the ammonia in the URL
06:41that tells you how much bicarbonate
06:44was added to the blood, if any.
06:47By common is lossed in the urine.
06:50Obviously you're not aesthetic.
06:52Scription is lowered by that amount.
06:55No one knew information that
06:58actually has been interesting,
07:00because we always assume that
07:02ammonia industry being a gas,
07:04it will cross the cell membrane
07:07without any problem.
07:09But it turns out actually unique
07:12transporter for ammonia board
07:14on the Lumiere side side,
07:16as well as on the urinary side so that
07:19you have a transporter that transport
07:22on your across the cell membrane.
07:26Into the urinary space, so that then
07:29that could actually trap hydrogen,
07:32therefore plus is generated,
07:33ends up in New York and this end
07:37experiment showing that in mice
07:39being loaded with the transporter or
07:42without transfer and transport is much
07:45choruses glycoprotein molecule without it.
07:50Without it,
07:50the transportation is much lower level
07:53than with the transporter being available.
07:56So clearly,
07:57again,
07:57just like urea,
07:59that we thought was always crossing
08:02membrane water is suddenly got
08:05all of these need their own fast
08:08facilitated transport across
08:10the cell into your own space.
08:12Now, what controls ammonia excretion?
08:15The major one base status,
08:18so acidemia the cell generates the
08:21motor ammonia approximate trivial,
08:23which ends up in the URL,
08:27but the other control is serum
08:30potassium again,
08:31that has to do with the fact
08:34that hyperkalemia is also should
08:37be intracellular acidosis.
08:39Hyperkalemia just the opposite,
08:41and this is basically review.
08:44Putting all the data together,
08:46showing that the higher the
08:48level up from potassium,
08:50the lower the level of urine ammonia,
08:53so does illustrate line relationship
08:56between the strong potassium ammonia
08:58that ends up in the universal
09:01ammonia generated in the proximal
09:03tubule from glutamine delivered
09:04to post on trivial from deliver.
09:07Just summarizing it that
09:09when there is a simialr,
09:11the signal from the liver to the kidney.
09:15By delivery of glutamine to the kidney.
09:18It's not really substrate limited reaction.
09:21There's always an operator mean that then
09:24allow generation ammonia based on at best
09:27shadows based on the potassium asados.
09:29The ammonia then preferential
09:31ends up in the urine.
09:32Some of it ends up in the Cortex back to the.
09:37From back to the plasma will
09:39relax a bit about coordination.
09:42Rated in Proxamol tribute to remind
09:44you again that cell pH and strong
09:47potassium or the major regulator
09:49of diammonium generated an ex
09:51created title as it can increase,
09:53but the increase really has to do with
09:56a PK or tactical asset for spayed and.
10:00Angel occurs as urine becomes
10:03more and more acid image.
10:05The highest amount is about 3 fold.
10:08For ammonia can increase by about 10:30.
10:12So come back to the initial
10:15initial classification.
10:16One could look at the ammonia as giving you a
10:20signal to were the problem is in development.
10:24Africa casino says if the ammonia
10:27is high in is probably GI loss,
10:30with kidney being normal.
10:32Norris, Molly,
10:33normally Placid in your making more
10:35ammonia to get rid of hydrogen ion
10:38and you're a back hallway.
10:41It is slow.
10:42It is probably renal either from loss of
10:45bicarbonate or from defecting by coordinate.
10:48Generation.
10:51No,
10:51unfortunately it doesn't measure ammonia.
10:53We have actually worked met
10:54with him a couple of times.
10:56I said,
10:57could you actually measure it
10:58so we don't have to deal with
11:01this very complicated concept?
11:02All your in onion gap?
11:04Or really you're in Korean gap.
11:06Not gonna spend much time on it,
11:09just to remind you it we only measure urine,
11:12sodium plasma question and chloride.
11:13We are really ignoring ammonium,
11:15which is a major carry-on in the URL.
11:18So if you don't measure that,
11:20that's what's missing in your end.
11:22Normally this reaction will be less than 0.
11:27In normal individual, could you confirm?
11:29Ultimately you are.
11:32If you have metabolic acidosis and
11:35kidney is normal kidney this morning.
11:37Normally the ammonia production goes up
11:40dramatically so that this becomes much,
11:43much lower than zero becomes
11:45more negative as it carry on.
11:48Not an animal gap,
11:50basically.
11:51If the problem is that the kidney
11:54cannot make ammonia,
11:55should ammonia production is low then this?
11:59Formula becomes positive the more positive.
12:03The lesser amount of Mone ya it is not
12:05a one point reaction relationship.
12:08It is basically a very quarter relationship.
12:11Here is a study done but battle
12:13here showing that if you look at the
12:16amount of ammonia urinal and yeah the
12:18more negative and you're a patient
12:21with diarrhea where they have a lot
12:24more Iamonia your depression with
12:26RCA with very little ammonia. It becomes.
12:29Positive here it becomes negative if
12:32you have a normal individual on conium
12:35chloride or the individual has diarrhea.
12:39So that's really the measure study
12:42showing the relationship between
12:44urine and gab and ammonia in the URL,
12:46and it's not a one to one relationship.
12:49Surely a qualitative election?
12:52The limitation is the fact that you cannot
12:55use this formula if the urine is alkaline.
12:59Other unknown in the urine bicarbonate.
13:02Or if there is presence of other anions,
13:05especially in the hybrid acidosis,
13:08but you have better hydroxy butyrate.
13:10I should acetate in the URL, you cannot use.
13:14This formula is only true about urine
13:18is acid in pH or a less than 6.5.
13:21Ann, if their clinical situation
13:23is such that there's no other non
13:27integer N or the normal animals.
13:29So you can use your smaller gap
13:32doesn't have that limitation here.
13:35The idea is to calculate your as
13:37well ality sodium plus potassium
13:40model by two plus urine, urea,
13:43nitrogen, urine, glucose,
13:44all of them in millimolar and then have
13:48the lab measure it was missing from
13:51this formula is NH 4 plus and is an ion.
13:55So image four will be your
13:57or smaller gap as measured.
14:00Management Calculator by two.
14:02If you do that,
14:03you have a reasonable one to one
14:07relationship between ammonia
14:08in the urine and or smaller.
14:10Job is not affected by presence of order.
14:15It can be affected if you have other
14:19smaller active material in your end.
14:22That's not very common man.
14:24It all is good example person's going
14:26to buy it or infusion turning up the
14:29account from my account into your
14:31end to use this formula is easier
14:33to use and it's more accurate years.
14:37Let me now move on to Jeanette Smartie,
14:40again with sight on understanding normal
14:43Physiology of acid base regulation.
14:46Again, initially going to cut proximate,
14:49trivial.
14:49And remember, here we have a sodium,
14:52hydrogen sodium hydrogen exchanger.
14:54Sorry on the Lumenal side and showed
14:57him by copper and bilateral side.
15:00Here we are looking at that cell,
15:03so initially going to look at is
15:06there any mutation in hydrogen
15:08sodium exchanger that should result
15:11in RTA in human being?
15:13There's a mouse model of that mutation.
15:17That looks like thanks a lot,
15:19Yeah,
15:20but there's no chase report in human
15:23yet for imitation in this molecule has
15:26been reported to cause RTA to several.
15:29Patient reported from Central America
15:32will assume a dominant proximal RTA,
15:34but when they looked at,
15:37this molecule was perfectly normal.
15:39They still don't know were
15:41there mutation is in.
15:43Maybe in a regulatory protein that relates.
15:47To this transporter,
15:48but it has not been proven.
15:51The major reason for genetic approximate
15:54ETA is actually a mutation in a
15:58sodium bicarbonate electrogenic
16:00transporter on the blood side.
16:03Basically transferring bicarbonate
16:05generated in the cell proximal
16:08tubule cell back to the circulation.
16:11This is also more recessive
16:14possible out there.
16:15And this patient usual
16:17presently showing status.
16:18They have carrot, cataract, theraband,
16:20croata party at the same time,
16:23and the obscene misclassification.
16:26So does a major.
16:28Genetic type of structure like here is
16:32in this sodium bicarbonate transporter.
16:37Now let's look at the.
16:40Cortical collecting duct where we are talking
16:42about the generation bicarbonate here.
16:45Obviously the whole situation and much more
16:48complicated the approximate trivial an here.
16:50The first molecule that was looked at
16:53how did and it appears it would do love.
16:56The work was done at Yale.
16:59Actually in Richfield,
17:00if translab were they looked at
17:03patients for mutation in this molecule,
17:05the molecule that is able to secrete
17:08hydrogen into the aerospace.
17:10Generate a one to 1000.
17:13Gradient between hydrogen concentration
17:16in Serum hydrogen concentration
17:19in the urine space.
17:22This molecule is a very
17:23large molecules can see.
17:25These are different subunits of air.
17:28Is primarily cytoplasmic the smaller area?
17:32Interest in membrane is called everyone.
17:36This is the V0 concept.
17:38This is where the ATP binding site is.
17:43We generate the energy for hydrogen
17:46to crossover into the universe face
17:49to secretly vision this molecule.
17:52Agility Pierce is a molecule data,
17:55so the mutation that has been recognized
17:59or patient bill or zoom or recessive.
18:0348 majority be sensorineural deafness.
18:07Not all but majority for the same
18:11molecule exist in the cochlea.
18:15In the V1 region.
18:16The B1 subunit is worth the initial mutation,
18:21but discovered in the 15 patient issue
18:24reported 13 had mutation in this subunit.
18:28Then the next mutation in the V0
18:32region in the a subunit of Visual Je.
18:37And as I mentioned,
18:39both of these are present in the cochlear
18:43hydrogenate EPS molecule in the near here.
18:47Most recently,
18:48hillebrant in Boston has reported a
18:53single patient now were not submitted B1.
18:57Or submitted a but submitted see.
19:00As being said,
19:02computation.
19:02This was a large series about looked at.
19:07One single patient had a submitted
19:10C Mutation causing this alati.
19:14Report it with a very interesting protein
19:17that's involved in traffic of heart rate,
19:21EPA's.
19:21Today membrane and this so called with
19:24you or 72 molecule is one other one Fox
19:282 that's also involved in this process.
19:31The point I'm trying to make is
19:34database still don't have all the
19:36genes that explains all the patient
19:39that we see I will show you some
19:42of the human studies but how many
19:44of them we understand genetically
19:46harmony or play meaning unknown but
19:49these three finding or the letters
19:51in to describing the jeans in.
19:53Popping up here.
19:56The next molecule I was looked at
19:58is obviously Ionone Exchanger One.
20:01That transfers bicarbonate for chloride.
20:05In the.
20:06The blood side of the portal collecting
20:09duct cells in the collector cell type way.
20:13Ann,
20:13this molecule is a very large
20:17molecule as shown here.
20:19The same molecule exist in the red cell,
20:22a one is shared between the kidney
20:24and dressed up in red cell is as
20:27a larger N terminus that anchors
20:29into the cycle's skeleton obdurate
20:31cell and maintain the
20:33shape of red cell the way
20:36that the Shepherd red cell is
20:38maintained is by an exchange of 14.
20:41Looking up to the door so lot of Psycho
20:45skeleton through the N Terminus.
20:47This enter Mrs.
20:49Shorter in the kidney and Exchanger.
20:53So that all the abnormalities of red
20:56cell as far as Cytosis, Orla, Cytosis,
20:59acanthocytosis really relates to a
21:02mutation in a one in the red cell, OK?
21:06Now then the.
21:08Patient have the renal one.
21:11And those cover that cells are
21:14actually separate population
21:16and show you why that is this.
21:18Or now the red cells that are due
21:23to Mutation in AE one in Russia.
21:26Now if you look at the Human Studies
21:29is a large normal dominant vessel,
21:33RTA primarily in this molecule,
21:36mutation or Gen 589.
21:38But there's also a group in Southwest
21:42Asia in Thailand, especially,
21:45but a mutation mutation in.
21:49The next molecule recognizing
21:51multiple in this one.
21:53Although patient will have water cytosis
21:56and this a lot here or compound heterozygous,
21:59there are two separate mutation.
22:01One in the EA, one of the kidney,
22:05the other man in the region color
22:08described that's involved in red cell shape.
22:11Here is this study just published.
22:13They looked at 15 patient.
22:16In Southeast Asia.
22:1813 of them only had a kidney problem.
22:22And these are the sight,
22:24these blue ones or the cycle
22:27mutation that they saw in the kidney.
22:30This one is such a mutation in red cell.
22:34Two patient patients 14 and
22:36patient 15 per compound.
22:38Heterozygous mutation in the red cell
22:40region as well as in the kidney.
22:43This one patient have seen actual
22:46documentation only reported endorsement,
22:48dyslexia.
22:48So so far there are patient
22:51had bought disease,
22:52but red cell and the kidney.
22:54They tend to be there all so far.
22:58Or complain because I guess the
23:00majority of this alot here had no
23:03red cell mutation and they just
23:05have this a lot easier and also
23:07just have Orla Cytosis or Esper
23:10Cytosis and noticed a lot here.
23:15This is one of two large studies looking at.
23:18Human studies,
23:19what are the mutations are comma?
23:22And as you can see, the imitation in ATP.
23:26180 PS is much more common.
23:29This is now this on this or mutation in 180
23:33PS accounting for about half the patients.
23:38The one in an exchange rate is
23:41much less common, only 10%.
23:44But here in this group of
23:47patients closer about 10%.
23:50Had mutation of unknown significance and a
23:54large number about 1/5 of them were unknown.
23:59A much larger study done
24:01internationally published a year ago.
24:04Unfortunately, 39% of them.
24:06This group were not a study.
24:09They were unknown basically.
24:11But here again,
24:13as you can see the mutation,
24:16ATP SB1.
24:23The mutation rate EPS were much more comma.
24:27This is the population at EPA.
24:30Is these two 35% more in open
24:34iclone only accounted for about 15%.
24:37So hydrogen ATP is is a much more common
24:41reason for genetic RTA done an Exchanger,
24:44but there also a missing population
24:46where there may be a mutation of
24:49unknown significance or they have
24:51not been discovered that presenter.
24:58No. Much of the patient up hearing loss.
25:02Tend to be the group that
25:05have hydrogen ATP's mutation.
25:06A rare occasion bit on an exchanger have
25:10certain nerola so clinically in professional.
25:13Do you see a child has sensorineural
25:17deafness with RTA is highly likely
25:20that their problem is actually
25:23inheriting Atps region and not
25:25in our exchange of Reacher.
25:28But again, with a steady,
25:29maybe a large number Garland, No?
25:34What about renal function?
25:36What happens to patient lab genetic
25:40character? Overtime if we look
25:43at them when they are children.
25:45Most of them have sikidy
25:47type one 2/3 of them.
25:49I had abnormal renal function.
25:52But it means that the third of them.
25:55Have abnormal renal function.
25:57That's about 1/3 but the majority of security
26:01to a small number of security 3 or 4.
26:04When they become adult.
26:06This sub is.
26:07It changes now more than half or security
26:11to pasembur around 30% or security
26:14three or security for at this point.
26:18Rate of decline in GFR is actually
26:21quite low at .8 ML per year on average.
26:25But remember,
26:26G4 remains quite a stable until
26:28you're about 40 there Geoforest
26:30changing when you're quite young,
26:32so that by the age of 40 they already
26:35have lost significant allergy far.
26:38So the aging of the kidney
26:40occurs earlier than that.
26:42And here looking at comparison group
26:46or no more population in in his study.
26:50Looking at those with endangered
26:53form 840 and seeing who has.
26:56See KD of any type is much more common here.
27:01We talking about 76% of this RTA.
27:05Only 14% of this population.
27:08Otherwise normal euro population.
27:10But when we age,
27:12even overpopulation have some
27:14kind of renal disease.
27:1744%.
27:17Some of them are CKD, 234 etc.
27:21But almost 100% of the Salatia
27:24now have decreasing cheerful.
27:27So comparative populations at the
27:29same age that they have much more.
27:32The likelihood of Elon declined
27:34to have renal failure at
27:37the age of 40 and above.
27:41No, there is a type one or two
27:44together that you could imagine.
27:46It has to do with coronavirus type tool,
27:49but that's occurring.
27:51Anhydrase that is shared between Proximate
27:53Tribune and cortical collecting duct.
27:56Type 40 is only in the brush border
27:58and we have no brush border in the
28:02quarter collecting back and this is the.
28:05Give out why cell syndrome.
28:07These operational person
28:09with a super process.
28:11Cerebral calcification mental retardation,
28:13shortest others,
28:15visual impairment and conductive deafness
28:17at that point is also more excessive,
28:22and due to carbon hydrates.
28:25Deficiency typed.
28:29There also genetic hyperkalemic
28:31RTA to very quickly.
28:33These are called Hyper Aldo
28:36Pseudo Hyper Aldo Type 1.
28:39And these are two types.
28:40Either you have a problem in sodium channel.
28:44Is sodium channel that doesn't open.
28:47And his suit hyper Aldo Type 1.
28:51Inserting channel or a problem
28:53in mineral Corticoid Receptor.
28:55So middle court have no effect in both
28:59of these are low level is quite high,
29:03but although effect is minimal because
29:05added the channel is our normal order
29:09receptor America record as an access.
29:11These are children who have sought
29:14wasting hyper kaylie make failure
29:17to develop and become unable to
29:20Gnosis they usually are quite sick.
29:23At very young age,
29:251 depleted between a failure and very high
29:28under level but very poor response at all,
29:32not sure.
29:34Type 2 is boring syndrome.
29:38You have heard much more about it in
29:41the talk on potassium regulation,
29:43not expending time.
29:45These are individuals have problem.
29:48Add this sellable in the wink.
29:52System and as a result they have an
29:55open sodium chloride transporter.
29:58Typical hypertensive hyper Kelly make.
30:00With Lauren in normal,
30:02although a normal chair for their
30:06usually present where hyperchloremic
30:09telecaster doses with hyperkalemia.
30:12So there's some larger genetic sort here.
30:17If it's proximal RTA.
30:19So far in human being,
30:22the problem is in sodium bicarbonate
30:26transporter and disorders more recessive.
30:29If you are disallowed here.
30:31Most commonly is hydrogen ATP's mutation.
30:34Less commonly is an exchange of Mutation.
30:39If you have a mix proximally
30:41stone in human being is imitation,
30:44the calling on highways.
30:46It was type retail imic RTA.
30:49Type 1 mineral Corticoid Receptor
30:52Mutation or the inactive Mutation.
30:54Type 2 is a wing pathway mutation.
30:59Causing hypercalcemia where to
31:01have recording talk acidosis.
31:03The type tool,
31:04or hypervolemic hypertensive the type one
31:07or hypervolemic hypertensive sword waster,
31:11but they're very differently.
31:13Presentation when you talking
31:16bout hyperkalemic art here.
31:18So let's move on to clinical presentation
31:21and how do we see this patient in the clinic?
31:25Now to again give you a cartoonish
31:28view of how I visualize the problem.
31:33Here is a normal individual.
31:35Code filters, about 5000 milligrams,
31:37a back order today.
31:40And.
31:43Array absorbs all that $5000 back order 8.
31:47The urine pH. Your impatience, I said there's
31:51absolutely no backward into your end.
31:54Whenever you actually load them,
31:56bigger case drops below 5.2.
32:00In proximal RTA, at the beginning they
32:03have 5000 milligrams about court filter.
32:07Summary absorbed alot examining urine
32:11urine is Marshall Clinic Clinic.
32:15As the amount of Bicarb in this room falls,
32:18it matches with the real George with
32:21the ability in urine becomes asset.
32:24So you have variable urine.
32:26pH depends on the filter loads of
32:30bicarbonate. There's a lot here.
32:33There's a constant leak.
32:35In the back, carbonate and three
32:37in the back corner regeneration.
32:39A simple to look at it as if it's
32:42part of a unity internal bicarbonate.
32:45So no matter how much it fills her load,
32:48is it high or below?
32:50There's an obligatory loss of
32:52bicarbonate soda.
32:53Urine is always Auckland.
32:56In hyperkalemic type,
32:57which I will talk at the end, the problem
33:00is not in reabsorption of bicarbonate.
33:03The urine is always acid.
33:05The problem is purely in reclamation
33:08in regeneration, back, or relate.
33:11The problem is generation about pneumonia
33:13as required to regenerate bicarbonate.
33:16That's loss in daily basis from
33:19the food stuff that beat.
33:22So the urine pH should be helpful
33:26initially in separating one from the other.
33:29No,
33:29the classical is to do on window chlorite.
33:33Asked recently it has been proposed
33:36that because ammonium chloride
33:37is not very appetizing,
33:39many children become nauseated with it.
33:41You have to give a fair amount
33:44.1 gram per kilogram and do that
33:47a different one with Rosa might
33:50plus full record is on hasn't been
33:53forced missed initial study,
33:55but group in England,
33:56but they showed an in control.
33:59I'm gonna price Europeans blocks in
34:02every control normal individual hominum car.
34:05I'll order.
34:06It also dropped in their population when they
34:10were given source mods full of Corazones.
34:13And, uh,
34:14this a lot here,
34:16and none were I able to acidify,
34:19wait, I'm gonna chloride,
34:22or with Rosa my full Corazon.
34:25The only difference is that William
34:28chloride urine pH stays low for much
34:32longer time than with record design.
34:35And again, you're impatient could
34:37not drop to normal in either group.
34:40And it went on a chloride or Phillip
34:43Orizon Grossman,
34:44an ammonia generation is much higher
34:46if your chloride,
34:47and if we can further.
34:51This has not been proven to be under
34:54percent sensitive and percentage specific.
34:56Here's a study where,
34:58as you can see below,
35:00milk, right?
35:01In normal population all 40 were
35:05able to acidify.
35:07However, when they are given flu,
35:10cortisone for some I only 30.
35:12Three of the 40 for able to acidify.
35:16So it was not sensitive enough.
35:19Actually there were false positives
35:21which are shown here here.
35:23We are only 17 that really had
35:25a problem acidifying whatever.
35:2724 we throw some artful localism.
35:31In the population of the stone disease.
35:33In again,
35:34in England and a percent sensitivity
35:38was reported.
35:3924% specificity with a positive
35:42critic value or 70 four
35:455% negatively raquelle 100%.
35:47So if the person cannot acidify the urine.
35:52They proposed I should
35:54give ammonium chloride.
35:56If they are satisfied with reporters on,
35:58there's no need to do that.
36:00That's really,
36:01really the bottom line right now.
36:03My point is that they almost rarely need.
36:07Either the two test it should be able
36:10separated individuals clinically quite well.
36:12It's a rare patient that you
36:14have to actually acid Lord,
36:17forgive for some actual person.
36:20Potassium is low in both
36:22proximal RTA as well,
36:24just on normal to high in Type 4.
36:28This area,
36:29while is a very common presentation,
36:32has not been fully explained.
36:35Hypokalemia is definitely due
36:37to renal wasting of potassium.
36:39Is not corrected when you correct
36:43acidemia by giving sodium bicarbonate
36:46or other alkalinizing solutions.
36:49Do you not care?
36:51Wasting is partly due to loss of sodium
36:54potassium bicarbonate in the URL.
36:57Part of it in the subgroup of Abbott
37:00Russell induced RTA is due to leakage
37:03of potassium because of the whole that
37:06is created by Apple in the distal
37:09convoluted in cortical collecting duct.
37:13There is.
37:14Enact interest activity because
37:16of interstellar acidosis,
37:18and that causes more sodium
37:22wasting and potassium wasting.
37:24There's also increased add or if
37:27there's one dictation associated.
37:29We are not sure which ones are dominant
37:32event in the usual, just larger.
37:35Obviously if there was a defect in hydrogen,
37:38potassium ATP S which is part of.
37:42Quarter collection dashed bank.
37:44Would explain RTA and applique
37:47limia but there has been no mutation
37:51reported in human in this transporter.
37:54There is one toxin.
37:56Naturally, inhibitors transporter run a date,
37:59but that is not associated with
38:02hypokalemia or disloyalty at present time,
38:06so we are still are not totally sure.
38:10Why have a training base so comma so
38:14common in both proximal and distal RTA?
38:17Some other reasons are included in the slide.
38:22Now, what about your ammonia?
38:24Would that be helpful?
38:25It is annoying all types of RTA is not there.
38:29Core of the Physiology right
38:32ear and over the causes.
38:34Now you know Bologna.
38:36So you can actually say that
38:38it's easy to decide what RTA is
38:41initially by looking at Harmonial.
38:43True, la GI loss if it is low,
38:48you're in either loss,
38:50total loss of bicarbonate excuse me,
38:53or defecting back already generation.
39:01If it is due to loss of Microbially.
39:05If the urine pH lesson is about
39:075.3 and the patient is academic
39:10data disallowed here your patient
39:13is seen by color 14 urine pH is 6.
39:17You already have a diagnosis.
39:20You don't need to ask your low dissipation.
39:23However, if the urine pH is.
39:266. And if I can't, is 19,
39:31it could be either distal or proximal RTA.
39:35All you have to do.
39:37Is acidified individual to less
39:39than 14 decide which one it is?
39:42That's when I'm on in chloride.
39:44Or frozen my records not ask your cell phone.
39:50If potassium is normal or high.
39:52Most likely talking about Typo Rakia.
39:55So measuring the urine ammonia
39:58making strong potassium should.
40:00Lead you fairly close your final diagnosis.
40:03The only thing will remain is the urine pH
40:07obtained with strong potassium is low enough.
40:11To make a diagnosis definitively know enough,
40:14I think about carbon 1415 is a
40:16cut off if you're below that,
40:19you already have your diagnosis.
40:24Assume Alexia is present in Proxamol
40:27occasional present in this storm that let's
40:31call an absent in Type 4 RTA naturally,
40:35tax is very helpful.
40:38Is absent approximately.
40:40Almost always present in this style.
40:43An absence type for so a patient that
40:46you see in the clinic, the proximal RTA.
40:50If they have a stone disease,
40:52you have really question that diagnosis
40:54most likely to have this alot.
40:57Yeah, I mean if calcinosis or Natalie
40:59Tharsis type for you, are they in?
41:02No because of a classroom and
41:05almost over sub some renal failure.
41:08No, the reason for nephrocalcinosis
41:11nephrolithiasis has to do
41:13with during citrate.
41:15Which in proximity is normal and
41:18I would come back to why it is
41:21normal but slow in this a lot here
41:23and again it is relatively normal.
41:264 degrees of renal failure.
41:29Citri level drops very low failure,
41:31but it's normal for the gorilla
41:34failure intact for RTA.
41:36Now citrate is filtered normally
41:40into the Proxamol Tribute.
41:44Is reabsorbed the amount that is utilized
41:47in the mitochondria has to do with cell pH?
41:51If the cell is ademic match of citrate,
41:55enter dramatic andreya grocery citric
41:58acid cycle to generate bicarbonate.
42:00But if cell is alkaline.
42:04The citrate ends up back in the serum.
42:07Some of it ends up into your hand.
42:12If there's a sadena in the cell,
42:15the urine citrate is very low.
42:18Note, almost all the citrate is reabsorbed
42:21in across similar in the patient.
42:24Has RTA but cell is not a city.
42:27Macon will come back to that.
42:29Then set the secrets ends up in the area.
42:32I know one individual beer citrate usual
42:35more than 300 milligrams as it cut off.
42:37That is normal.
42:38Another separator is them into your hand.
42:41If the cell has no more pH.
42:45Now this is what a stone can
42:48look like in this a lot here.
42:51These stores are almost
42:53always calcium phosphate.
42:55Not calcium oxalate.
42:56The reason being that the stone in these
42:59patients is becausw of defect in urine,
43:03pH and high calcium.
43:04In New York.
43:06This differently study done by the group
43:09and UCSF many years ago look at night
43:12to patient RTA and they had type 180,
43:16not type 2 distal proximal and 30 type 4.
43:20They look at border bone and the
43:23kidney 18 who had never calcinosis.
43:26Ordered this RTA.
43:27Ask you Malaysia and Rick.
43:30It was seen in track two only in this group,
43:34so bone disease is very different
43:36than the stone disease and that
43:39helps you a lot in the clinic in
43:41separating or theater being proxamol.
43:44Most of this stuff.
43:46Ask your opinion or dude
43:48acidaemia was also common intact.
43:50Four she can commonly have
43:52underlying liver disease.
43:53Here again looking at genetic RTA only and
43:56what they looked at Africell Stenosis.
44:00And this is percent of the
44:02patient and the calcinosis.
44:03It will almost 100% with 180P A's almost
44:07under percent had never calcinosis,
44:09but only 20.
44:11Persistent had naturally Cyrus.
44:13This is also true that almost all
44:16weird unexchanged effect have never
44:18calcinosis while only close to half
44:21of nucleotides is so difficult
44:24is much more common disallowed.
44:26Here it doesn't matter what you do too.
44:31But more common in patient
44:33will have 180 PSD effect.
44:38No preview why this alati's stone?
44:41You have hypercalciuria becausw of acidemia
44:44exchanging hydrogen for calcium in the
44:48bone and have low citrate in the URL.
44:50So calcium then buys phosphate is insoluble,
44:54and because you're in the alkaline
44:57calcium phosphorus stone is pH dependent
45:01and a precipitate forming system.
45:04In proximity air, that's been long debate
45:06about why and they have normal citrate.
45:09Well, that measurement actually
45:11has not been done that commonly.
45:13The reason is what Peter pointed
45:15out to in the last lecture,
45:17which is that this patient
45:19actually have an alkaline serum.
45:21There's the problem is they cannot.
45:24Can they not take the generated bicarbonate?
45:28From the cell into the
45:32blood doctor circulation.
45:34But in the effect isn't an exchange.
45:37So, so the cell becomes alkaline.
45:40Are they kept by Cortona be
45:42transfer or call me on the cell,
45:45prevent reabsorption citrate into the South?
45:48So the euro succeed in normal.
45:51This is the most studied in genetically
45:54Proctor RTA due to Mutation in this one.
45:58Is this mutation in this molecule again not?
46:03And reporting human being again,
46:05the problem is.
46:07Different and it may motor citrate
46:09may be different in the URL.
46:12Depends on where the problem is.
46:15At this point,
46:16the problem bicarbonate transfer
46:18is seldom is alkaline.
46:19These patients have low urine pneumonia.
46:22Becaused effect in this transfer
46:24abnormal restrain and there
46:26are your normal urine calcium.
46:28They don't develop a storm in the candy.
46:33Classification Approximal RTA basically.
46:35Primary is a familiar with sporadic
46:38such tender in the majority have
46:41basically a disease does involving
46:43the whole truckload tribute and
46:45they have really Fanconi Syndrome.
46:48Cystinosis Wilson.
46:49This is being genetic,
46:50but in the whole series of them
46:53in adult or we see often either a
46:56light chain disease or low casually
46:58situation with short term force,
47:01approximate review and most of
47:03them have drug you starting a
47:06drug induced box last year.
47:08Ifosfamide custom covering
47:10anhydrous inhibitors.
47:12This all again primary familiar,
47:15sporadic secondary systemic disease.
47:17The most common adult sugar,
47:20but others comma.
47:21Primal sources and lupus never
47:24calcinosis as a primary event.
47:27Secondary arterial obstruction,
47:28or the ones that we usually worry about.
47:32Income piloti is when you
47:34have normal electrolyte.
47:35Lifeless signify the individual's
47:37head load the individual next time,
47:40not acidify the urine and the problem is.
47:44That they begin with inability to.
47:49IK St Harrington iron you have interstellar
47:52sidosis they have low urine citrate.
47:56They developped africell
47:57cyanosis that quarter damage.
47:59Does Schumer kidney that then causes
48:03no you remone then they develop
48:06complete urine ammonia or decreases.
48:10This little function here looking show
48:13damage as a secondary event taking what
48:16is called incomplete or fear to complete,
48:18like here.
48:20In computer today is seen in children who
48:24have for sure valve defect in the urine,
48:27in the urethra and this patient
48:30when they have incomplete or K.
48:32Your height is lower than normal individual.
48:35You look.
48:36Complete RTA there.
48:37Much shorter than normal individual
48:40as reflected on the bike
48:42or and that they have no RTA normal
48:45height or TL Ng hide Ng bicorne.
48:48This basically tells that in kids.
48:51You have to maintain normal bicarbonate
48:54to make sure that they grow.
48:56That is basically the bottom line or
48:59immune disease can cause are here.
49:01That's what we see in adult sugar.
49:04The most common, the bottom line is complete.
49:08RCA is seen in about 3 to 5% or sugar
49:12in completed artists in about the third
49:14or patients with Sjogren's syndrome.
49:18In the largest population for
49:20right now with shoulder,
49:22the most common renal finding is RTA.
49:25Here's another very patient in China.
49:28Of those 95 outside RTA,
49:31the majority night 1095 dischord
49:34here four had franconi.
49:37Proximal part here,
49:39as well as a small #120I and they
49:43have severe is Sean nephritis.
49:45As you can see here,
49:48an autoimmune disease damage in their
49:51design and sometimes proxy material.
49:54This is 1 patient Bob seed
49:57insurance syndrome.
49:58They were missing harriton Atps
50:00pump compared to normal kidney.
50:03This is using a mouse antibody.
50:06Is that really true? In all patients.
50:10With defect in.
50:12Short term,
50:14this adult acquired art here
50:16is only one patient word.
50:18This asthmatic border in a larger
50:20study of 11 patient bought alignment
50:23that looked at problem in Harrison
50:2580 PS problem in Corona and highways.
50:29Probably none exchanger amazing
50:30thing is that a day don't with Alisa,
50:34Lottie with control being those that
50:37kidney disease and those who are
50:40normal there problem in all three areas.
50:43So in patients who have ordering
50:45units on the Fridays here,
50:47do the sugar and the problem is not only one.
50:51A specific transporter.
50:52The problems in the sun.
50:55All of activities related to urgent
50:58scription or actually abnormal beta.
51:00Alternate EPA's bait calling and
51:02I raised or bid on exchange.
51:06This is especially true Logan when
51:08they look at anybody to corner and I race.
51:11These are patients who are controlled.
51:14Real is location sugar without.
51:18Without RTA Shogun with RTA.
51:22Antique organ high rise higher in
51:24those who had RTA higher still in
51:28those who had strong hair without
51:30hair compared to control but higher
51:33begins with the last two books.
51:36And if you look at the amount of an
51:40antibody to covenant high waist shown here.
51:44Compared to buy Korean,
51:45serum or potassium in this room,
51:47there's a correlation between
51:49the amount and a body,
51:51and these two finding in the syrup.
51:54So in human being with us a lot, yeah.
51:57In a subgroup that everybody is
51:59coming on Holidays and that's the
52:02other group that have both proxamol.
52:04As well as this a lot here it is shorter.
52:06To secure this,
52:08start commonly had problem in all
52:11components of this or how to signature.
52:14Is a mouse model tried for the
52:18concept with human?
52:19Common highways anybody against them
52:22they cannot access the fighting on it.
52:25So to summarize, in order in munis lot,
52:28yeah, the problem is very general.
52:31In the cell, Tribulus Dozer,
52:33Proximal and this thought that comma,
52:35Nevada body carbon hydrates.
52:38Treatment in alkali therapy
52:41in this all is not difficult.
52:45.5 to one Mil Quality Julie enough.
52:48You have to also replace potassium.
52:51The motor alkali you need based
52:53on age it drops as the patient
52:55gets older here because you're
52:57growing the making the bone,
52:59they may require formula transport kilogram.
53:02When they become adult,
53:04one to two milligrams and laugh in
53:06Parola patient .5 to 1 milligram
53:09per kilogram is commonly enough,
53:11but you need to maintain normal
53:14bicarbonate in children to grow.
53:17Proximal is very difficult to treat.
53:19Treat online disease and high
53:21level of alkali commonly waste
53:23law by calling they give them.
53:25Then you need to replace the potassium.
53:28It has been commented on other potential
53:31treatment void will treat them given Karzai.
53:34All his tricks that you can use
53:37occasional vitamin D's use all
53:39of those to increase team or by
53:41coordinate impossible trivia.
53:43Very briefly, type a lot.
53:44Here is the most common that you will see.
53:48Name it doesn't with patient
53:49with chronic kidney disease.
53:51Remember they have a low back
53:53ammonia in the urine.
53:55They and they have a high serum
53:58potassium that is the market forecast
54:01for the commonly have decrease in GFR.
54:05And this patient is a very older
54:08study actually done a deal where
54:11they found that hypo Aldo was present
54:1580% hyper any 80% but 20% had no
54:18more running normal although unable.
54:24So the first large of this station have
54:26a problem in running although circuit.
54:29Either no more running low Aldo.
54:32Lauren in Palo Alto or a small
54:34group and or a normal although
54:36and lack of response in attribute.
54:39This has to do what you guys know very
54:42well that you need to make rain in JG.
54:45Operators has to go through
54:47this whole series of events.
54:49Including a little gland this morning
54:52to either potassium or to run in,
54:54and a fairly response in the tubular,
54:57you can interrupt the cement
54:59at many different places.
55:00I'm not going to go through that.
55:03You basically have drugs to block
55:05at every step in this one to cause
55:09arterial due to medication from a
55:11step one all the way to the end.
55:13Their medication right now that would
55:16do that. Easier to make a diagnosis.
55:19These are the lesser medication.
55:22Available to you on this slide.
55:25Here the treatment should be initially.
55:28Discontinue all the medication
55:29that impacts on potassium.
55:31Restrict dietary potassium.
55:33It doesn't enough.
55:35Diabetes is very common in this patient.
55:38Make sure they are well controlled diabetics.
55:42Then treat Metallica Sidosis.
55:44With my card or some alkali.
55:47One depletion.
55:48Worsens hyperkalemia versus Rick
55:50acid or salts trigger it.
55:53Now those work use loop diuretic use the
55:58side effect of diuretic hyper hypokalemia.
56:03Test to tree Topper chillemi
56:05a metabolic acidosis.
56:06If all of those fail,
56:09then think about using floor enough
56:11in the crossed some now takes like
56:14can be used to newer polymers
56:17available to control potassium,
56:19but you really need to use that.
56:22Really. Go back to very basic.
56:26Trade my streetable.
56:27An easy for the patient to manage
56:29excellent is not very pleasant.
56:32New parliament are quite expensive tools.
56:35Let me finish my summer.
56:36I do all the time.
56:38Everything that we know in acid base
56:41or the work of individual sub work
56:44for last two centuries trying to
56:47figure out what the hell is going
56:49on about to remember 2 individuals.
56:52One is Alright.
56:54An article that thing every not
56:57follow should read published in 1946
57:00in the article is only 80 pages long
57:03and want to read it available on the web.
57:06With beautiful drawing done by or
57:09bright and he described for the first
57:13time a group of patient with tubular
57:16insufficiency without polymer insufficiency.
57:20Who had had to commit,
57:22or Castillo says some had never
57:25calcinosis under for the Tarsis
57:28they had under uses the water.
57:30Spectacular response to alkali
57:32will disruption of natural casino
57:35says triple nephrolithiasis and
57:37he said this is not the norlite.
57:40Richard is not due to renal failure.
57:43This is a traveler disease
57:46not available of these days.
57:48Alright There's a beautiful table.
57:51In which she tries to separate
57:53proximal from distal,
57:55he makes a major mistake in
57:57the final outcome.
57:59Taking the approximal were
58:01due to increase in organic.
58:03I said production because these
58:05patients had a specific disease
58:08fanconi syndrome and they were
58:10wasting organic acid as well.
58:12We know that that's not really true.
58:16Albriton came with this pathway,
58:18exactly what I'm trying to teach today.
58:21That the problem is in decrease
58:24your among your expression.
58:25This causes custom results in from
58:28the bowling cause a simulation
58:30hypercalciuria discourse.
58:32Significant snow says not realizes this
58:36may cause a pickle simuel increase.
58:40Increase phosphate and becausw
58:43of calories is hyperkalemia.
58:45This is in 1947, that's what he said.
58:52Second page personal to remember Oliver
58:56wrong major article published in 1959.
58:59I've had a number of pages here.
59:02This is about 54 pages article.
59:06He is the one who created on a chloride test.
59:11It's a large number location.
59:1311 of those had RTA introduced owner protest
59:17separating proximate from this last year.
59:20Oliver Ron wrote his last first
59:25Article 1959 that's equal #7.
59:29He wrote his last article.
59:31In 2012 he was working on the
59:37same question it in 1959.
59:402012 You talking about 52 years chasing the
59:46same question he gave up and he died early.
59:51This is what All Blacks say in one
59:53of his talks, he said I've told you
59:56more about our soup process.
59:58Well, I know what I've told you is
01:00:01subject to change without notice.
01:00:03I hope I have raised more
01:00:05questions that give an answer.
01:00:08In any case, as usual.
01:00:10And not working necessary.
01:00:12That's a message to all the Young Fellows.
01:00:16Your many questions not
01:00:18answered by your faculty,
01:00:20or if there's a lot to be excited about.
01:00:23Thank you very much.
01:00:25I'm done.
01:00:26If there's any question would
01:00:28be happy to answer.
01:00:33NASCAR had a quick clinical question.
01:00:38Does a Ki kick in injury of influence?
01:00:45Acid handling. Very good question.
01:00:49There is a recent article published
01:00:52by the group at Northwestern.
01:00:55Where for the first time?
01:00:57They made that comment that
01:01:00shroom bicarbonate is not a good
01:01:02marker for how to Kennisis Asset.
01:01:05Well, that's the last.
01:01:08Attempt at maintaining and or bicarbonate.
01:01:11That you're looking.
01:01:12You're not looking at the
01:01:14events happening in the kidney.
01:01:15And they introduce the concept of
01:01:18urine citrate divided by urine,
01:01:20Creatinine E as a measure
01:01:22of the renal response to.
01:01:25I said like that's normal.
01:01:28Despite normal bicarbonate.
01:01:31That's the normal response.
01:01:33If that's abnormal and North Run
01:01:36by companies normal's still the
01:01:38kidney is facing a severe intercel
01:01:41acidosis by responding normally. Not.
01:01:44This study has not been done in HCI.
01:01:48So we do see definitely.
01:01:51Academia Inukai if you look
01:01:53at bicarbonate application,
01:01:54blood pressure is normal.
01:01:56Is it drop about 2 to 3 milligrams
01:01:59per day if their GF far is
01:02:02less than 10 ML per day?
01:02:04So that would mean that they're not making.
01:02:07Enough ammonia in your end to replace
01:02:10about cotton being loss at that time
01:02:12was the actual mechanism in HCI.
01:02:14I suspect it has to do again with ammonia
01:02:17production and attract ourselves.
01:02:19Tubulars are undamaged,
01:02:20be well to do that,
01:02:22but that is study has not been done any API.
01:02:26It's also difficult to do because
01:02:29everything is scheduled day by day,
01:02:31so they studied by more and his
01:02:33group Sequoia and the group just
01:02:36published is really in chronic
01:02:37in the disease that they propose.
01:02:40Urine, citrate, urine, creatinine,
01:02:41at least from creatinine,
01:02:43may be a good way of looking at
01:02:45the kidney response class anemia.
01:02:52NASCAR, yes. That there's that there
01:02:56should be a distinction between renal
01:02:58acidosis and renal tubular acidosis.
01:03:00In the there's no such thing as the go Mary,
01:03:04or that's it those.
01:03:07That's a very good question, I think.
01:03:10If the bottom line and patients will
01:03:13have any on gap between gas and or
01:03:17says because the fact that we love
01:03:20failure and you're unable to handle
01:03:23for Spain and sulfate organic assets,
01:03:25they also have a lower ammonia.
01:03:30RTA so in some way the bottom line
01:03:32is either you have a problem in the
01:03:36tribute becaused you have a problem
01:03:38in the function or you have a
01:03:41problem with keyboard while you have
01:03:43a normal renal function GF are but
01:03:46the trouble is not respond to that.
01:03:48Find the separation is helpful in
01:03:50terms of thinking about the patient.
01:03:53That you do see Fisher with perfectly
01:03:55normal creatinine level GF are or
01:03:58significant acid anemic and the question
01:04:00is that why is that they're looking
01:04:02at the onion gap is helpful as you do
01:04:05to increase production organic asset
01:04:07or is it a problem in the kidney in
01:04:10term of redirection back hardening?
01:04:12So I think Leslie cell floor
01:04:14but different logical level.
01:04:16Is it comes back to the same problem.
01:04:20Hi I have another question about this
01:04:22in a Ki not every once in awhile on
01:04:26consoles someone will notice that a
01:04:28patient with an AK I has no acidosis,
01:04:30that's non gap and a memory nonsense.
01:04:33Urine studies but if someone's not
01:04:35at their study I always kind of
01:04:38think that in the midst of them AKA
01:04:41I would not be the time to kind of
01:04:44evaluate someone for in RTS and that
01:04:46you know it should be should wait for
01:04:49the kidney to return to baseline.
01:04:52Steady state and then see is that correct?
01:04:55That's definitely correct.
01:04:57No question about that.
01:05:00If you have a patient was clearly
01:05:02change day by day.
01:05:03Commonly there are many other
01:05:05things happening and that's why I
01:05:07that's why you're in the hospital.
01:05:09That's going to make a decision
01:05:11about is that I think that really
01:05:14is not the time discussed.
01:05:16Idea time is when the patient is back
01:05:18to normal walking around the streets.
01:05:21Look at how they're handling your
01:05:23normal acid load and then deciding
01:05:25is that normal or not normal.
01:05:33Well, you're out of time.
01:05:35Thank you so much.
01:05:36I will see you guys next week.
01:05:38Thank you, bye.