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ACUTE KIDNEY INJURY
JAMES R. JOHNSTON, MD
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I’d like to thank the organizers for inviting me to talk about acute kidney injury. I would point out
that the University of Pittsburgh Medical Center is a hot bed of activity in acute kidney injury and we
have two of the world’s experts in acute kidney injury here in the role of Dr. Saul Oleski who is
Chief of the Nephrology Division a the VA and also John Kelman in the Critical Care Department.
And it’s sort of humbling for me to give a talk about this when I work with people that are really
defining the field.
Nonetheless I will give it my best try. My disclosures are a few, I will assure you that I hold less
than 10,000 dollars stock in each of these companies and that if I owned 1% interest in Pfizer I
would not be giving this lecture. I give no promotional talks, haven’t done that for years nor am I a
consultant. I just own stock.
Today’s roadmap, we’re going to do a general overview of acute kidney injury, I’m going to talk
about some of the definitions that we currently use, the magnitude of the problem which has changed
quite a bit and also a general approach. So that if you really were pressed for time you could leave
after this first part of this talk, I will have covered most of the basic principles. Later on, we’re going
to talk about the other items that are shown here.
Dr. Crate asked me when I told him I was giving this talk if there was anything that was really new in
acute kidney injury and I had to tell him no and he laughed and said I didn’t think so. But there are a
couple of things that have changed and I think we’ll go over those. So acute kidney injury is defined
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broadly as a rapid change in glomerular filtration rate, this change occurs over hours to weeks, most
nephrologists will tell you that in the modern era it’s over hours to days and it results in the retention
of nitrogenous waste products. We measure BUN and creatinine and we’ve been measuring urea
since 1825, it was the first one that was measure and it’s still the one that’s measured. There are 800
uremic toxins and the reasons we measure urea and creatinine is because they’re cheap and they’re
easy to do.
The definitions, non-oliguric is more than 500 ml of urine per day. Oliguria is less than 400 to 500
mls per day. And anyone that’s ever rounded for me knows why oliguria is defined as this level of
400 to 500 and the division people are smiling because they know this definition too. 500 is the
minimum amount of urine that you need with two perfectly functioning kidneys to excrete the solute
load that you take in, in one day. So that when you fall below 400 to 500 you start to accumulate
nitrogenous waste products and therefore fall into the category of azotemia where you accumulate
these nitrogenous waste products.
Anuria often known as bladder sweat is something where you fall below 100 to 50 mls of urine per
day and then finally uremia is the condition you get whenever you start to have symptoms that arise
from azotemia.
We usually detect acute kidney injury whenever blood urea nitrogen starts to increase usually about
10 to 20 per day, serum creatinine increases, this varies. If it’s somebody that’s as nonmuscular as
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me my creatinine might only go up about .8 per day. If you were looking at Arnold Swarztenegger
during his time not as governor but as Mr. Olympus, Mr. Olympia whatever it was, he might have
probably gone up at a rate of about 2 to 2.5 ml per deciliter per day simply because he had so much
muscle mass.
The other thing that we most frequently get called for is that the urine output falls and this is really
the most unreliable indicator of acute kidney injury. In 50% of the cases, the urea and the creatinine
are going up even though the urine output has not fallen below the level of 500 mls per day.
The other thing that you need to understand about the markers are that I can go in and have both of
my kidneys completely shut down and go from normal GFR down to nothing in a matter of minutes
to hours. And yet the marker that we look at in this particular case which is creatinine will go up
very, very slowly even though renal function has completely stopped. The usual rate which we talked
about is about .5 to 2.0 milligrams per deciliter per day and we use that as nephrologists as an
indicator of how long the patient has had acute kidney injury. If we’re lucky enough to know that the
patient had normal creatinine a few days ago and then we’re called to see the patient and they have
no urine output and their creatinine is 3, we will go back two days based on a average increase of 1
milligram per deciliter per day and say that the insult happened about 2 days ago. It will vary
depending on the severity of the insult. But the prime thing that I wanted to point out about this
marker serum creatinine is it really lags behind the loss of GFR and therefore is a poor marker.
There’s a big search right now in nephrology to find other markers that are a little bit more precise
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in determining the time of the insult, statin C and Indol which is a urinary expiratory product have
been looked at but these are not ready for prime time yet.
You can have errors in the urea that fool you into thinking that there is acute kidney injury present
when it really isn’t. And these are due to increased urea production without decreased excretion and
those include increased protein intake. It’s very common for us in the intensive care unit to see
someone that’s getting nitrogen feeds and have their BUN go up very, very much despite the fact that
their degree of renal insufficiency is not that great. GI bleeding, you break down membranes of the
red blood cells, you break down the hemoglobin itself, that generates urea. Catabolic states, being
septic, being on corticosteroids cause increased muscle breakdown and that increases urea generation
and then you can have catabolic drugs such as tetracycline that increase urea production as well.
The same could hold true for our other marker, creatinine. You can get increased release from
muscle so that if you’re in – we’ll go back to London during the blitz and a building falls on you and
you have muscle damage from that, you release free form creatine kinase from the muscle cells that
causes creatinine to go up. You can have interference of secretion of creatinine, excuse me, from
proximal tubules due to interference from trimethoprim or cimetidine. And you can also have
interference with the lab tests. We still use the Jaffe assay here, the Jaffe assay has been used for
about 130 years. If the patient has a high glucose, if they’re on cephalosporin, if they have keto-acids
present like with PKA or if they’re on antifungal like flucytosine that can cause a fault elevation in
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the creatinine. So you have to know the medications that the patient is taking in order to adequately
interpret this.
This is one of the areas that catches you’re attention when you do a literature review on this. When I
gave this talk ten years ago I mentioned that the incidence of acute kidney injury in the hospital was
about 1% to 3%. It’s now 5% to 8% in the United States for all hospital admissions. Some of this
may be because of better coding, in other words people are coding for acute kidney injury but if you
look at the absolute numbers based on a variety of studies, it does seem like it’s increasing. It now
is recognized that it complicates about 65% of intensive care unit admissions. This means that in an
institution like ours where we have 160 intensive care unit beds, that we see an awful lot of acute
kidney injury. It is frequently iatrogenesis imperfecta as in the doctors trying to dry someone out,
giving them medications that aren’t adjusted for the degree of renal insufficiency and so on. And out
of this large number of patients about 30% with acute kidney injury are going to require some sort of
renal replacement therapy. So what does this mean? Well this is a plea to the house staff, it means
that there’s job security for nephrologists, you will always have a need to have a nephrology
department come in and take care of your acute kidney injury, it is our most common consult for
nephrology. I am very fond of the Pittsburgh consult for acute kidney injury which is needs dialyzed.
Only in Pittsburgh, never happened in Boston.
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The other thing is that at any given time at Presby there are 80 to 110 patients being seen on
nephrology services and for those of you that have rounded on the nephrology you know that they’re
busy services and roughly one half of those will have acute kidney injury at any given time.
The risk factors for acute kidney injury are the ones that we’re already familiar with, advanced age,
race African-Americans are much more prone to this, men are much more prone to this, decrease
renal blood flow due to volume depletions, medications especially the calcineurin inhibitors in this
institution and sepsis with preferential decrease in renal blood flow into the kidney despite the fact
that total peripheral resistance goes down, resistance in the kidney goes up. Diabetes which is a
preexisting kidney damage and cardiac hepatic renal disease all of which will predispose as well.
One of the things that I find interesting is that a recent exposure to nephrotoxins and we have an
expert on nephrotoxins in the audience for contrast nephropathy, Dr. Wiseborg has done quite a bit
of work with this. But if you’re exposed to nephrotoxin on Friday and then you’re exposed to another
nephrotoxin on Monday, your risk of having acute kidney injury from the second nephrotoxin
exposure is increased more than from the second nephrotoxin exposure, so they are additive.
The complications are what we – I have learned to respect congestive heart failure, a multitude of
electrolyte abnormalities and one of my favorite topics and the reason I’m a nephrologist is because
very single system in the body is affected by uremia from hair growth and skin health all the way to
platelet dysfunction, pericarditis, cardiac function, seizures encephalopathy, acquired immune
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deficiencies, nausea, vomiting and anemia, it just goes on and on. Just as a warning for those that
may round with me and oh, gee, a couple months, I go through every body system on rounds and it’s
up to the attendees to be able to tell me what they know about it.
So our first question, which of the following best describes the mortality rate in acute kidney injury,
20%, 40%, 60% or variable depending on the setting?
Six responses, okay. Okay, we give credit to the 50% that know how to take exams, the answer was
obvious because it was the only verbal answer, all the rest were numeric and it was also the longest
answer. So you could have answered this question without knowing anything about it. But the
answer is that’s it’s variable depending on the setting. And it’s not good. If you look at mortality
rates in the general series a lot of them uncontrolled, there are about 5 separate definitions for acute
kidney injury in the literature, 50% general mortality, 70% mortality in the ICU series whenever you
have acute kidney injury. And if you go and do a comparison of sepsis and acute respiratory failure,
acute kidney injury is of equivalent importance in terms of mortality in the intensive care unit. So
it’s something you have to take care of.
This gives you an idea about the setting. So for our preeclamptic patients that we have down at
Magee and we’re having a run on them this month, your mortality is about 15%. If you have an
aminoglycoside or you have a contrast induced AKI your mortality is about 30% and if you look at
patients that have sepsis your mortality varies but it’s around 60 to 90%.
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This is an old study by Chertow from 1995, what he looked at is the incidence of mortality here on
the Y axis and then the year so we really started doing dialysis for acute kidney injury back in the
1950’s. It was a chosen population tended to be relatively young and few people and you saw the
mortality was about 30%, as we started to broaden and have increased access to hemodialysis and
peritoneal dialysis more and more people were enrolled into these studies and we got up to about a
60% mortality in 1990.
The mortality as been seen, has improved since that time, there have been a number of studies
looking at it as well, Ukino in 2005 published what is one of the largest studies of acute kidney
injury, there are 29,000 patients in this study. We’re finally catching up to the cardiologists so that
we can have clever names for our studies, this is the BEST-kidney trial beginning and ending
supportive therapy for the kidney. What they looked at, their definition of acute kidney injury was
anybody that required renal displacement therapy and of that group 60% died. If you required
CRRT or if you required intermittent hemodialysis, you did not do well. The PICARD study, again a
nice little name, the program to improve care in acute renal disease which was published in 2004,
showed that a 37% mortality which showed a real effective case mix. And amongst the five centers
of study, 618 patients, the mortality ranged anywhere from 24 to 62 percent. I will guarantee that
here at our institution where we are a quaternary center we are going to be much more staying to the
high side of mortality because we see a patient population that is much more acutely ill and has many
more comorbidities and we’re a referral center.
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So the basic diagnostic approach for this as always is history and physical with a strong emphasis on
medications and preexisting conditions. The second component of this is an emphasis on volume
status. I used to win bets at the Brigham by finding edema on patients that the house officers
couldn’t. One of the areas that is frequently not examined is the small of the back in a bed ridden
patient or their hips. You have to look at those areas to see whether they’re not volume overloaded
or not.
You also have to look at the urine sediment and electrolytes both the chemistries in the blood and the
chemistries in the urine and acute tests that are important. Imaging studies in this day and age can
be limited more or less to the ultrasound and then some invasive tests. Fluid challenges, fluid
challenges have to be limited because of the increased incidence of abdominal compartment
syndrome which is directly related to excess volume resuscitation. Checking the CVP and the last
resort is doing a biopsy and I really don’t think we do enough biopsies at this institution to really
settle the issues.
The therapy is – if its broke fix it.
Adjust renally excreted medications, correct fluid and
electrolyte imbalance and nutrition. And of all the things that we have done over the last 40 years for
acute kidney_ injury these things are the most important things that you can do is to feed your
patient. At least 20 to 30 kilocalories per kilogram per day and at least a protein intake of 1.5 grams
of protein per kilogram per day. You really don’t need any more than that. And then renal
replacement therapy with continuous modalities, intermittent hemodialysis and peritoneal dialysis is
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up there because it was one of the modalities I used here as a house officer quite frequently. But it’s
really not used anymore for renal replacement therapy in the acute setting.
There are a variety of different ways of estimating renal function, Cockcroft-Gault is one, again the
formula is present pretty much on everybody’s iphone if they have the typical drug sources that are
available with their med tables and such. And the MDRD estimate, the MDRD estimate is not
validated in a lot of populations, it’s not validated in the elderly population. And these are more
useful whenever the patient presents to the hospital and you have some idea about what their baseline
renal function is. If you do not have an equilibrium state and you’re trying to calculate what GFR is,
you’re not going to know. Think back to that diagram that I showed you where you lose your renal
function in one day, you have no urine output, your creatinine is 1. Well by the MDRD you’d have
normal renal function but you don’t. Next day if you had a creatinine of 2 you still don’t have any
renal function but you MDRD would tell you that you have 50 percent renal function. So these have
to be looked at with a great deal of patient information and clinical acumen in order to get the
appropriate estimate of renal function and _____ dose your renal medication.
Consult nephrology early. Interestingly enough we do take care of dialysis patients and acute kidney
injuries pretty well. We’re actually better at the lab at looking at the urine, that’s been done in a study
by O’Hare a couple years ago. And we can intervene and help prevent acute kidney injury from
getting worse so please call us early.
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Your major etiology of acute kidney injury are the ones that we all learned a long time ago, kidney
doctors haven’t gotten much smarter is pre-renal where the kidneys are intact and underperfused.
There’s intrinsic renal where there is parenchymal damage to one or more of the components of the
kidney, these could include the blood vessels, the glomeruli, the tubules from being efficient and
then there can be post renal which is obstruction to urine flow.
And that leads us to the next question which is what is the most common type of acute kidney injury.
Is it prerenal acute kidney injury, is it acute tubular necrosis, is it obstruction, is it AKI
superimposed on chronic kidney disease or is it acute interstitial nephritis? We did better, this time
we got ten and prerenal was the answer that was picked. And this is sort of a nasty question for me
to ask you because the trick right answer is acute tubular necrosis. But most of your cases of acute
tubular necrosis develop because of prerenal azotemia.
I just reviewed in the ____ Fourth Edition of Comprehensive Kidney – Comprehensive Clinical
Nephrology and he still refers to this diagram which is from a study in Spain by Liano in Kidney
International in 1996, shows that ATN was the number one cause back in 1977 and 1980 prerenal
40.6 and a variety of smaller causes. 1991 if you look at this prerenal is 21% and ATN was 45%.
Acute-on-chronic has gone up with an older patient population and obstructive has gone up with an
older population as well and they accounted for more.
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If you look at some of the more recent data what you’ll find is that sepsis in the Uchino study,
remember 29,000 patients studied in this particular paper, sepsis was associated with acute kidney
injury 50% of the time. Major surgery primarily cardiac surgery was the second major cause. Low
cardiac output, hypovolemia and medication, these were the top five in that study. Other causes were
the hepatorenal syndrome, trauma, cardio-pulmonary bypass, the abdominal compartment syndrome
which is really achieving much more attention because blood flow to the kidney is very, very
sensitive to increase pressure in the abdominal compartment. And the current definition for this if
you are to do bladder manometry is 150 mls of saline in the bladder, that the kidney is at risk with a
manometric reading of 12 and you’re definitely going to get damage with a manometric reading of
greater than 20. So that’s something that if you have someone with abdominal surgery who is had
aggressive volume resuscitation you should be doing bladder manometry in order to look for this
particular condition.
Rhabdomyolysis is very common, we have a lot of trauma here at ____, I found at that we have 5000
trauma cases a year here, rhabdo is very frequently associated with trauma and obstruction in our
older population, more of a problem at the VA than down here.
So let’s go through prerenal acute kidney injury. Again, this is a car it doesn’t have any gas. The
kidneys are fine, functionally intact but underperfused. There’s a variety of reasons why you can
have this, you can have true volume loss secondary to hemorrhage or ascites volume redistribution in
that particular case. Or you can have decreased perfusion of the organs from the aorta associated
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with poor pump at volume distribution. You can also have inappropriate renal vasoconstriction and
we see this most often with a calcium urine inhibitors. The causes are multifold, they all result in a
general or localized reduction in renal blood flow. The biggest one is here, GI renal, blood losses,
skin losses, you can lose as much as a liter of sweat in an hour if you’re exercising in a hot humid
environment and if you don’t properly volume expand you can get into acute kidney injury with that
or if you overdo it you get into what’s runners hyponatremia where they drink too much dilute
solution. You can have decreased effective circulating volume due to heart, liver or kidney
problems. You can have medications especially the nonsteroidals, ACEs, radio contrast is a
vasoconstrictor. The hepatorenal syndrome, sepsis causes blood flow redistribution, large vessel
disease a rare cause, an embolism, cross clamping with aortic dissections or aortic aneurysm repair,
renal artery stenosis, small vessel disease with vasculitis, all which cause ischemic acute kidney
injury.
One of the most important tools in looking for this prerenal state is the fractional excretion of sodium
which simply stated is the fractional excretion is the excreted sodium over the filtered sodium, this is
the formula again it’s present in most of your – I hesitate to say PDA’s but your cell phones and
smart phones and such, you can call this up quickly so you don’t have to remember it. And if you
substitute urea up here, you can also get the fractional excretion of urea which can be used to assess
the prerenal state in someone that is on a diuretic. If it’s less than 30% that’s indicative of a prerenal
state as well.
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Again, medications and volume losses are important. The volume exam is critical. Make sure you
measure orthostasis if you can for a patient in the intensive care unit, this can be tough. Skin turgor
is important for your patients that are between the ages of 15 and 45 and don’t have much sun
damage, you can check skin turgor on the forehead. For the patients that have decreased or greater
than 45 say 45 to 65 you can check skin turgor on the sternum and the last group and please go in and
if you’re going to feel the thigh of an 80-year old woman, let her know that you’re going to feel her
thigh to check her skin turgor and that you’re not being fresh. It’s really important for good patient
relationships.
But skin turgor if you have decreased skin turgor in a patient who has not had a detected disease such
as cancer that’s indicative of about a 5% decrease in total body volume. Feel the eyeball turgor and
it’s decreased, push on the eye and it’s like pushing on dough, that’s 10% volume decrease. Look for
signs of CHF and sepsis. Because the kidney is not damaged the urine sediment is bland. The urine
chemistries will reflect an underperfused kidney, so it will be sodium retentive, less than 20 for urine
sodium, a fraction excretion of sodium less than 1% and Uosm not greater than 500. This also tells
you that tubular function is intact. That there’s no damage to the tubular at this particular time. You
can get a BUN to creatinine ratio of greater than 20 to 1, I know that that’s practically taught and I
find that that’s not very useful in this day and age. You have to many other things that are affected
the urea.
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So the therapy is to correct the underlying disorder. It’s to gradually replace volume losses, treat the
cause of the volume loss, treat the hepatic, cardiac or renal disease and stop offending medications.
ACEs have to be stopped right away regardless of the cause of the acute kidney injury, if someone’s
creatinine starts to go up you should really stop the ACE inhibitors. Diuretics is one of the reasons
why we frequently get into problems, cardiac surgeons like their patients dry, liver surgeons like their
patients dry, transplant surgeons like their patients wet and you have to go in with that sort of
knowledge ahead of time so that you can make the argument cogently and again calcineurin
inhibitors that decrease renal blood flow primarily.
Now the major cause of acute kidney injuries tubular in this particular situation, this will follow
prolonged prerenal azotemia or a nephrotoxic insult. And one of the things to remember is that
there’s a gradual transition between the prerenal state and acute tubular necrosis. And you can find
this sort of crossover between the two especially where you have someone that has really very classic
acute tubular necrosis but they still have a very low urine sodium and a low fractional excretion of
sodium. Urine findings in this particular case tell you that they’re transitioning from one form to the
other. Generally by the time you have tubular damage, you probably should give a volume
challenge just to see what’s going on but most of the rest of the time it’s going to be supportive care.
It has been said that the end in acute tubular necrosis is a misnomer because if you long at renal
biopsies, our patients with ATM, the great majority of them do not have evidence of necrosis of the
cells. One of the terms that’s come up is vasomotor nephropathy which suggests that there’s an
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imbalance between the vasodilators and the vasoconstrictors affecting renal blood flow. And that that
decrease due to this state is the primary cause, they’re saying that this is an non-repairable cause of
decrease in the blood flow, that it’s due to an hormonal imbalance. One of the major things that
happens when this is prolonged is that the cells swell and die and that there are some structural
changes that occur and oh goodie, you left my slide out. I thought for sure this slide wouldn’t stay.
This is your normal proximal tubule which is the major site of damage in acute tubular necrosis, the
brush border, you have the integrins which are shown on the basolateral side and you have
membrane transporters at various places in the nuclei. When you make this ischemic and I used to
do this in the lab when I was a renal Fellow the brush borders goes away in 30 minutes, it’s gone. If
you make it hypoxic for a short period of time you’ll have no brush border after that.
The second thing that happens is that this is a transporting epithelium and it loses its asymmetry, you
now relocalize transporters that are supposed to bring sodium from inside the lumen out but instead
they get relocalized on the outside. And with this you no longer can effectively transport sodium
you start to get volume overloaded. There is accelerated cell death, increased apoptosis and necrosis,
eventually you will get sloughing of cells that will form tubular obstruction which may be one of the
major contributors to acute kidney injury in this model. And if you support the patient and are lucky
enough the kidney shows a fairly dramatic ability to repopulate itself, to grow back and come back to
normal. Usually not though with complete recovery. If you manage to survive the acute kidney
injury episode you’re going to have a variable degree of damage afterwards.
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The biochemical changes that have been identified are cytosolic calcium, reactive oxidative species,
effects on ADP, ATP metabolism, increased phospholipase, the changes in cell death and also
increased neutrophils coming into the area and causing inflammatory responses.
This is, should be now, permanently imprinted in your limbic system that history and physical is the
most important thing, you have to do a thorough exam and a volume status, medications. And when
a doctor goes in and does volume status, we go back a week or so. And we add up all the I’s and
O’s. We always make sure that we put in an extra 500 for insensible losses which is frequently
missed. If the balance is even, you say oh, the balance is even but if its over 7 days that patient has
lost 3.5 liters of insensible losses during that period of time - you have to account for. It may be
volume depleted because of that insensible loss.
Urine sediment is quite characteristic, you get these muddy brown granular casts. And urine sodiums
and urine chemistry reflect the fact that the nephron is no longer functioning. Urine sodium is
greater than 40, fractional excretions sodium goes up to 3% or greater and urine osmolarity is low
indicating that tubules don’t work.
Now this is, we see this about, this sort of classic ATN type of urine sediment probably about once a
week and we also see it with a variation on the theme like this one. And I will tell the house staff
that if you have a case and you think the patient has acute kidney injury, go down to the house staff
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lab on the 9th South Floor or come up and have somebody open the lab by the dialysis unit and go in
and look at the urine. And then take your cell phone and focus on the eye piece and get the image on
your cell phone screen and take a picture of it. There is an article in the New England Journal of
Medicine this summer about how to do that. And one of my Fellows Dr. Tan has been doing this a
lot. I don’t know whether the other Fellows are doing it or not but it’s one way that if you think this
patient has a red cell cast and you take a picture of it, you can come and show us and we’ll say yeah
it’s not a red cell cast. But at least we can see what you’re looking at and we can kind of get an idea
about what it is and vice versa, we can take pictures of it and show you what we’re seeing whenever
we look at the urine sediment. I was talking with Deb before this and it was really nice that we could
put this in the medical record and be on par with the gastroenterologist but it is a way of doing it.
When we see this, this patient has acute tubular necrosis, end of the argument. That’s what it is.
The kidney does demonstrate a really remarkable capacity to restore structure and function. Probably
only out matched by the liver and for those that do survive renal functional recovery will occur in
about 60 to 90% but not necessarily back to normal. One of the outcome studies that I reviewed for
this talk demonstrated that in the patients that survive their acute kidney injury, that fully 25% of
them develop end stage renal disease and had to go on dialysis. Another 25% percent of the survival
group ended up in a chronic nursing home situation. These data are incomplete because most of your
outcome end points are at the end of hospitalization and there’s no long term followup. But you
have to remember that acute kidney injury has long term effects on our patients. And I think that we
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generate a large number of the end stage renal disease patients in the Western Pennsylvania area
because of acute kidney injuries. Rod, I just did a shout out for you about acute kidney injury.
The intrinsic causes, we’re not going to spend too much time on because they’re relatively rare,
you’re really talking about an overall incidence of about 5%. Kidney doctors love them because
they’re unusual and they’re hard to treat. There’s a variety of causes, lupus is one of the ones that we
see quite frequently. IgA necropathy, Goodpasture’s we see a good bit of here, much more than I
would have thought. But they can be systemic or they can involve the kidney primarily. The
autoimmune diseases can be directed towards the glomerular basement membranes such as in the
case of Goodpasture’s. You can have antigen antibody complex disease such as in the case of post
infectious glomerular nephritis. In the presentation interestingly, respiratory illness is very frequently
an antecedent of vasculitis. So if someone has acute respiratory illness and starts to develop kidney
injury you have to be thinking of pulmonary renal syndrome. And then finally systemic disease flare
such as lupus is frequently associated with this.
This is a relatively cynical look at the diagnostic outline, the urine sediment you have to look for the
blood cell casts. You can do the renal Gropogram and it really is the renal Gropogram. This is sort
of a reflex for anthologist and a double stranded DNA to look for the lupus associated complements
to look for the five diseases that are associated with complement which are cryoglobulinemia,
atheroemboli, ______ post infectious and lupus, systemic lupus erythematosus and if you put those
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together they make an pneumonic comp, those are the ones that are usually associated with low
complements.
ASO and AHT for post strep, Hep B and Hep C titers, Hep C has been a growth industry for us
because of membranoproliferate GN associated with cryoglobulinemia and the gold standard for this
is renal biopsy. If you’re not getting a clearcut answer biopsy the patient. We now do our biopsies
under real time in the abdominal imaging lounge, they’re very safe and we can do them even on
acutely ill patients. So this is a plea to increase the number of biopsies you do.
I have never seen a red cell cast like this. This is pretty much a classic pigmented cast surrounded by
a plethora of red blood cells and one of the things to point out is it is indeed a cast, it’s not a clump.
This is clump, a cast has parallel borders and looks like a cylinder. These are the red cell casts that
I’m more used to seeing, again cylinder type of appearance, parallel sides and these very bland
looking cells on the inside, this is a clump, this is a cast.
This is one of the reasons why a nephrology Fellow would spend half an hour looking at a slide
whenever they are convinced that the patient may have a GN, it’s because if you find one of these
that patient has a glomerular nephritides and has to be biopsied. So it really pays you to look for
these.
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The last thing I’m going to talk about is obstructive renal failure which can be subtle or fulminant.
This part of my talk will have lots of stories in it. The etiology is it has to affect both ureters or it has
to affect the bladder outlet. Adults can have stones in both sexes as a cause. Men it can be benign
prostatic hypertrophy or prostate cancer. In women it’s nearly always a gynecologic malignancy. In
children it’s nearly always congenital specifically posterior valves.
As far as subtlety in patients when I was at the VA between 1992 and 1995, we had a guy that
walked into the ED up there and his chief complaint was I’m tired. And we said oh, that’s nice,
you’re tired. And we did the usual, we got the labs on him and any guesses to what his BUN was?
BUN was 400, his creatinine was 44. And his chief complaint was I’m tired. So we did a prostate
exam on him and his prostate was you know big. I’m not good enough urologist but I can estimate
within one gram of how big the prostate is and we put a Foley catheter in him and we were promptly
greeted with a huge diuresis and within two days his creatinine was down to 2. So I was thinking
over to you know what a big boy am I and I really solved this case and everything. Four days later
I’m at the VA still on service and another patient comes in to the ED with the chief complaint of –
guess what? I’m tired. And he gave us symptoms of urinary hesitancy in obstruction of about a
years duration and we measured his creatinine which was 34 and his BUN was 350 and we thought I
know what to do, I just had a case like this and we went and we tried to put a catheter in and we
couldn’t get it past the urethra through the os, it just was completely blocked. So we had to put
percutaneous nephrostomy tubes in him. And in this particular case I waited for the large rush of
urine to come out so I can amply rewarded with the European peeing boy fountain but I didn’t get
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JAMES R. JOHNSTON, MD
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that and he had to be on dialysis for 3 months. But at the end of that 3 months, he came off and he
was able to have a baseline creatinine of 2 and no longer needed dialysis support. He had prostate
cancer and they had to do a radical prostatectomy on him in order to fix his problem.
We have other cases where like in the case of my father, a Foley catheter was put in on the 7th floor
at Presby and they inflated the balloon in his prostatic urethra and he bled into his bladder and
promptly obstructed the Foley catheter and had acute kidney injury and urinary tract infection
associated with sepsis in two days. So you have to be aware that obstructions can be very quick or it
can be very subtle. In the first two cases that I presented to you, those patients had had urinary
obstruction symptoms for over a year and it was when we found these elevated levels that we finally
got them taking care of.
Lab is usually not very helpful, sediment is generally bland, urine sediment is all over, the sodium is
all over the place. If you catch it within the first 48 hours of the obstruction it will prerenal because
they have decreased their renal blood flow due to the increase hydrostatic pressure within the kidney.
If you catch them after 48 hours, tubulars are damaged and they no longer function. As far as your
imaging, your renal ultrasound is the best, it’s low risk. Keep in mind that it has a 10% false
negative rate and also keep in mind that whenever you are talking about your average Pittsburgher
who weighs 210 to 250 to 350 pounds, that your ultrasound has low sensitivity because of trying to
get through a pannus that’s 6 inches thick.
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JAMES R. JOHNSTON, MD
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So occasionally if you feel really strongly about and Dr. Zidell always felt strongly about it, would
make sure the urine was clean and then do a retrograde study if he felt that this was a problem.
How many of you have seen an IVP done in this institution in the last ten years? I haven’t. Most of
the time we’ll do an ultrasound. If the patient is too big we can do a noncontrast MRI or CT scan to
look and see if they’re obstructed. So this is where we have to turn down the pictures.
Give you a little course on ultra stenography. This is really a fun acute kidney injury to take care of
because your patients get better. So these are ultrasound of obstructive kidneys, this is the kidney
and this is the collecting system which is now black and when it’s black it means the soundwaves
go directly through it. Okay. There’s no reflection from this particular slide.
But one of the things you’ll notice is you have this post fluid accentuation and this is because the
fluid acts as a lens and tends to concentrate the sound waves and you get an increased echo back
from this area. So kidney obstructed, big collecting system, over here much the same, here’s your
kidney, collecting system is dilated and you get this post fluid accentuation, these are before and after
pictures. There you can see the kidney in sagittal section, you can see the collecting system and part
of the ureter, it’s blown up, kidneys here. This is after relief of the obstruction and now you see the
typical cortical margin and the typical medullary structures, no obstruction. The same thing here.
This kidney obstruction in the center indicated by the black. This is a rib shadow coming down
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JAMES R. JOHNSTON, MD
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across, sound waves can’t get through it so it’s shadowed and this is after relief of the obstruction
again with restoration of the medullary structures and the normal cortex.
The therapy for this is quite straightforward. If your obstructed relieve the obstruction. You can use
a Foley for urethral obstruction, you can do stents from below, you can do percutaneous nephrostomy
and one of the things to be careful about is the post obstructive diuresis.
One of my favorite cases here at Montefiore was up on the 10th floor and we were asked to see a
patient that was obstructed because of testicular carcinoma. We bypassed him, his renal functions
got better, his urine output went up and about 3 days after we’d seen the patient we had a consult for
please see same patient for diabetes insipidus. We thought okay, well this is interesting. And we
went back and what we found, by the way, your tubular function will usually restore itself after about
3 days. So this was 3 days out and we went up and we did the kidney doctor thing, we looked at his
I&O and he was getting 26 liters of fluid a day and he was peeing 25 liters of fluid a day. And what
had happened was, is that when you’re obstructed you accumulate urea and the nitrogenous waste
products which act as nonresorbable solutes. Also your tubules don’t work so that when you restore
blood flow and you start to filter again you make copious amounts of urine being driven by solute
diuresis and also by the failure of the renal function to return to normal. So you always want to
under replace these patients by about a liter. So if they make 5 give them back 4 and continue to do
that and eventually after 3 to 5 days they’re back to normal balance.
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JAMES R. JOHNSTON, MD
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What these guys did was take everything I had said to heart about acute kidney injury and they gave
him I plus O equals or intake equals output plus 500 and they kept replacing him more and more and
more until the poor nurse was hanging a liter an hour on this man, he was just merrily peeing it out.
So don’t chase the diuresis, remember that this is not something that you should do. Always under
replace patients recovering from obstruction.
Dr. Terling usually would laugh at me whenever I put this out about the indication for dialysis
because he thinks its too simplistic. But remember the English vowels AEIOU, they’re also the
Japanese vowels. A for acidosis, E for electrolyte abnormality, I for water soluble intoxication, I will
remind you that the Pitt students are back which means that people will be celebrating their 21st
birthday and we’ll be doing a lot of dialysis for acute alcohol intoxication. So it got to be one of the
major growth industries the next several months. O for volume overload and U for uremia, primarily
for uremia, platelet dysfunction and pericarditis.
Replacement therapy, PD is no longer used, intermittent hemodialysis, continuous renal replacement
therapy are two major ones. We nearly always use biocompatible membranes these days which cuts
down on hypotension during our treatment.
Dr. Palevsky directly addressed the issue of which is the best form and they looked at intermittent
hemodialysis and continuous renal replacement therapy, the largest study that’s been done on this
question to date and they found that if you gave an adequate dose in both cases that your outcome for
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JAMES R. JOHNSTON, MD
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equivalent between intermittent and continuous renal replacement therapy, I will tend to favor
continuous renal replacement therapy whenever I had a hemodynamically unstable patient.
But which of the following are effective in preventing acute kidney injury? Avoiding excess volume
depletion, correctly estimating GFR and adjusting drugs, avoiding nephrotoxins, 1 and 3 or 1, 2 and
3?
You guys are good. Alright you learned something. All 7 of you that answered the question. Okay.
It’s 1, 2 and 3. There are many, many things that have been studied to reduce risk. Do not give
diuretics if you’re trying – they actually worsen the chance of acute kidney injury because you
volume deplete the patient. Dopamine has been shown not to be effective and in some cases may
be harmful. Systemic atrial natriuretic peptide doesn’t work. Calcium channel blockers work if you
call the psychic hotline and say well my patient had acute kidney injury and if Cleo answers that, oh,
yes, your patient will have acute kidney injuries, if you give a calcium channel blocker and its been
demonstrated that that can decrease the incidence but you have to know that your patient is going to
do it. I don’t know, Steve is there large scale study been done looking at prophylactic calcium
channel blockers.
I know of one study in the Turkish transplant experience where they pretreat donors before they
donated and they had decreased rate of postop acute renal failure in the transplanted kidney. And
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JAMES R. JOHNSTON, MD
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then adenosine antagonists have been tried as well. We’ve also looked at thyroid supplementation
and the number of different things we’ve tried is protean.
One of the ones now that’s coming down the line is direct intrarenal infusion of ANP or BNP but
that’s not ready for primetime yet either.
So what I would like you to remember is that the best thing to do about acute kidney injury is to
prevent, correct volume depletion, expand your patients before they get dye contrast, avoid
nephrotoxins, adjust them appropriately, recognize presence of conditions such as chronic kidney
disease, acetylcysteine, does it help, does it hurt. I attended a talk at the ASN where the presenter,
one Dr. Weisborg said that last year there were more metaanalysis about contrast nephropathy then
there were studies on contrast nephropathy. No one knows if they help or not but you know that it
doesn’t hurt so we give it anyway.
And finally, low osmolality media probably does help. So in your contrast patients, volume expand
them ahead of time and try to use low osmolality contrast media.
I’m going to end the talk with a little plug for an acute kidney injury symposium which is being
help at the University Club on September 8, it’s going to be all day. We’ll go over basic physiology
and consequences of acute kidney injury and it will also be an opportunity to explore research
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opportunities at that time. And I think everyone is open to attend, right Tom, yes. And with that I’d
like to thank you and I’ll be happy to answer any questions.
Q:
There are a lot of studies of animal models, there are a number of different agents that have a
very positive beneficial effect on the course of acute kidney injuries. The problem with all these
studies is the agents are given at the time or prior to the initiation of acute kidney injury. One of our
challenges is to identify as early as possible when this is occurring and then to see if we can start
trying some of the therapeutic agents, if they’ll alter the course of acute kidney injury.
So you’re saying that we need a laboratory analog of Cleos from the psychic hotline?
Q:
Yes.
Q:
So let me ask a sort of a controversial management question. If you have somebody who has
oliguria acute kidney injury and your physical exam and data suggest that they are volume
replete, what – a not infrequent clinical practice is to try to administer diuretics to convert
them to nonoliguric acute kidney injury to make the acute management perhaps a little easier.
What’s your take on that?
Well I think most people would agree that if you convert to a nonoliguric form that their
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management is easier but if you look at the outcomes down the road, the mortality is exactly the
same. So if I do this I will do – and one of my favorite expressions is to sin and sin gravely. So if I
have somebody BUN of 50 and a creatinine – and they’re 70 years of age I’d give them 120 mgs of
Lasix. If they have a response I’d say that’s nice to have a response but I really tend not to continue
it. I just, it does make management easier but I don’t think it decreases mortality.
Other questions for Dr. Johnston, with that thank you very much.