Acute Kidney Injury
Workshop
Joel M. Topf, MD FACP
Nephrology
@Kidney_Boy • Joel.Topf@gmail.com
Acute Renal Failure
Joel M. Topf, MD
Introduction
Acute renal failure is “The House Moment” of nephrology. The patients go from normal functioning kidneys to zero function and at that point they either recover with no significant sequelae or they die. At that branch point, between total recovery and death, is the nephrologist
and she is selecting IV fluids, deploying dialysis, and determining the balance of atoms in order to nudge the patient toward recovery.
Goals
• Definition and staging of AKI
• Intra-renal AKI
• Etiologies of inpatient versus outpatient
acute renal failure.
• Understanding the Urinalysis
• Pre-renal azotemia
• Acute interstitial nephritis
• BUN:Cr ratio
• Ischemic versus toxic ATN
• Hyperkalemia
• FENa
• EKG Changes
• FEUrea
• Treatment
• Post-renal
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Acute Renal Failure
Joel M. Topf, MD
Table of Contents
History of acute kidney injury therapy .....................4
Definition of AKI ...........................................................4
Use KDIGO to stage the following cases of AKI ......6
Differential Diagnosis ..................................................7
Pre-renal azotemia ........................................................8
Diagnosing Pre-Renal ...................................................8
Questions on Pre-renal Azotemia ...............................11
Post-renal insufficiency ................................................13
Treating Post Renal AKI ...............................................14
Questions on Post-Renal AKI ......................................15
Intrarenal acute renal failure .......................................16
Diagnosis ........................................................................16
Clinical Syndromes .......................................................17
Questions on the Urinalysis ........................................18
Ischemic acute tubular necrosis .................................19
Toxic acute renal failure ...............................................19
Contrast Nephropathy .................................................20
Acute Interstitial Nephritis ..........................................21
Hyperkalemia ................................................................23
EKG Changes with hyperkalemia ..............................24
Treating hyperkalemia..................................................24
Question on hyperkalemia ..........................................25
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Acute Renal Failure
Joel M. Topf, MD
History of acute kidney
C. 15
injury therapy
In 1945, a 67-year-old woman in uremic
coma presented to Dr Kolff. He initiated
dialysis and she regained consciousness after
11 hours of therapy. This was his 17th patient after 16 consecutive treatment failures.
She lived another 8 years and ultimately
died of community acquired pneumonia.
D. >20
Definition of AKI
The study of AKI has been hampered by a
proliferation of definitions for AKI.
!
Dr. Haas in his laboratory with the first human dialysis machine in 1928.
Extracorporeal dialysis for humans was first
tested in the 1920’s by Dr. Haas. He treated 6
patients, all of whom died.
In 1943, Willem Kolff,
working in Nazi-occupied Holland, created the second human dialysis machine; and in 1943 he
dialyzed his first patient. This young
man with acute
nephritis died during
the therapy.
Question: If you invented a novel and unproven technology for the treatment of a
usually, but not universally, fatal condition,
how many consecutive failures (patient dies
during therapy) would you let occur before
you considered the technique a failure?
The classic text-book definition of acute renal
failure is “ An acute and sustained decrease
in renal function.” Unfortunately this accepted definition is hampered by ambiguity:
How acute? How sustained? How should
renal function be measured? Is the degree of
renal impairment important?
As clinical scientists studied AKI they needed specific case-definitions of AKI and each
researcher created their own. At last count
there were over 35 separate definitions of
AKI. This created chaos where one study
couldn’t be compared to another and has
hampered progress in the field of AKI.
KDIGO, the international nephrology guideline organization has established a consensus definition and staging system (1, 2, 3) for
AKI.
The KDIGO system replaces two other similar systems, the RIFLE criteria and AKIN
system.
A. 5
B. 10
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Acute Renal Failure
Joel M. Topf, MD
KDIGO
Change in Cr
Oliguria
Definition
≥ 0.3 mg/dl within 48 h or
≥ 1.5 times baseline, within seven days
urine volume < 0.5 mL/kg / hr
for 6 hours
1
1.5-1.9 times baseline or
increase ≥ 0.3 mg/dL
< 0.5 mL/kg/hr for 6-12 hours
2
2.0-2.9 times baseline
< 0.5 mL/kg/hr for more than
12 hours
3
3.0 times baseline or Cr > 4 mg/dL or
initiation of renal replacement therapy
< 0.3 mL/kg/hr ≥ 24 hrs or
anuria for > 12 hrs
The KDIGO system has been validated:
Validation means that as the AKI stage goes up the patient is sicker. This study shows an increase in both hospital mortality and length of stay with increasing AKI stage.
Fujii T, Uchino S, Takinami M, Bellomo R. Validation of the Kidney Disease Improving Global
Outcomes criteria for AKI and comparison of three criteria in hospitalized patients. Clin J Am
Soc Nephrol. 2014;9(5):848-54.
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Acute Renal Failure
Joel M. Topf, MD
Use KDIGO to stage the following cases of AKI
A 32 year old African American hair model with a baseline creatinine of 1.4 receives a contrasted CT scan to determine the source of bleeding following a
hysterectomy. Her creatinine 2 days later is 2.2. Her urine output over the last 8
hours is 640 mL.
A 28 year old Asian bank employee is in a motor vehicle accident. He goes for
emergency splenectomy and repair of a liver laceration. Despite aggressive use
of blood products and crystalloids he has been anuric since a foley was placed
14 hours ago.
A 62 year old white female who models for a national nursing home chain has
a PMHx of arthritis and hypertension. She presents to her primary care doctor
with symptoms of fatigue since starting ramipril for her blood pressure. Her
medications include ibuprofen 800 mg three times a day, chlorthalidone 25 mg
once a day, simvastatin 40 mg once a day and ramipril 10 mg once a day. Her
labs show a creatinine of 3.2 (baseline 1.2) and a potassium of 6.6. She states
she urinated a “normal amount” prior to coming to the office.
A 55 year old Hispanic comedian is admitted for decompensated heart failure.
His baseline creatinine is 1.4. On admission his creatinine is 2.2. He is given
furosemide and responds well. His oxygen requirement decreases, most of his
edema improves but his creatinine has gone up to 3.2. His urine output in the
last 8 hours is 460 mL.
A 82 year old nursing home resident with known diabetic nephropathy complains of an inability to walk. On exam he has an S3 gallop, rales in his lungs
and pitting edema in both legs and back. Labs show a creatinine of 4.8, a
potassium of 7.4 and a bicarbonate of 14. His baseline creatinine is 3.4. No
urine output has been recorded and the patient is unable to estimate his recent urine output.
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Acute Renal Failure
Joel M. Topf, MD
Differential Diagnosis
Acute renal failure can be divided into three broad etiologies: Pre-renal azotemia, intrinsic renal failure and post-renal azotemia (obstructive uropathy).
Using these categories one is able to quickly
narrow the differential diagnosis of acute
renal failure and determine the likely natural
history of the condition. Pre- and post- renal
AKI usually are quickly reversible and easy
to treat. They are often obvious from the history.
When the etiology of AKI is not obvious it is
helpful to be aware of the incidence of the
etiologies in various clinical settings. Multiple studies have shown that patients with
AKI upon presentation to the hospital have
different causes of AKI than patients who
develop AKI while in the hospital. Another
clue to the etiology can be the age of the patient. Pascual, et al. showed that as patients
age post-renal etiologies and pre-renal etiologies of AKI become more common at the
expense of decreasing intrarenal causes.
Question: Why might the elderly have more pre-renal
azotemia? Why do they have more post-renal failure?
100%
80%
17%
12%
11%
7%
56%
11%
20%
48%
39%
60%
40%
20%
29%
30%
65-79
>79
20%
0%
<65
Prerenal
Postrenal
Inpatient/Hospital
acquired AKI
Intrarenal
Unknown
Outpatient
acquired AKI
4%
38%
58%
17%
11%
72%
Prerenal
Intrarenal
Postrenal
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Acute Renal Failure
Joel M. Topf, MD
Pre-renal azotemia
No BP; No pee pee.
Volume depletion from any etiology decreases renal perfusion. If the body is unable
to compensate this will decrease GFR.
Heart failure and cirrhotic patients are both
edematous. These patients have total body
sodium excess but the amount of fluid in the
arterial blood compartment, the “effective
circulating volume” is decreased. This results in pre-renal azotemia.
As perfusion falls the kidney compensates in
an attempt to maintain a stable GFR. There
are two primary strategies to maintain GFR:
1. The first is vasodilation of the afferent
arteriole. Local prostaglandin production
triggers this response.
2. The second strategy is efferent vasoconstriction via the action of angiotensin II.
This increases intraglomerular pressure,
forcing more RPF down the glomerular
drain.
Both of these strategies increase intraglomerular pressure to maintain GFR. If
these strategies are successful, the GFR remains constant, the creatinine doesn’t rise
and the patient is not pre-renal. They are prepre-renal.
Question: What drugs antagonize the kidney’s ability for afferent vasodilation?
For efferent Vasoconstriction?
Diagnosing Pre-Renal
There are three tests you need to be facile
with to separate pre-renal azotemia from
intrinsic AKI:
1. BUN:Cr ratio
2. Fractional excretion of sodium
3. Fractional excretion of urea.
In volume depletion the kidneys become
sodium avid and retain BUN out of proportion to creatinine. This allows physicians to
make quantitative assessments of volume
depletion and make an accurate diagnosis.
BUN:Cr ratio
A BUN to Cr ratio over twenty is a reasonably accurate indicator of volume depletion.
This actually is an indication of the filtration
fraction at the glomerulus.
AT2
PGE
Filtration fraction =
GFR
RPF
The increased filtration fraction means that
the plasma proteins that are not filtered by
the glomerulus are diluted in less plasma
(because more of that plasma went down the
glomerular drain). This higher concentration
of plasma proteins exert greater osmotic attraction in the proximal tubules bringing
back more plasma water, sodium and urea.
Creatinine is actively secreted in the proxi!8
Acute Renal Failure
Joel M. Topf, MD
mal tubule and is not affected by this osmotic movement of water. The net result is normal creatinine clearance and decreased urea
clearance resulting in a rise in BUN out of
proportion to the rise in creatinine.
The calculation is easy to remember, doesn’t
require a calculator and is surprisingly accurate; however the test has some important
pitfalls. One can get a falsely elevated
BUN:Cr ratio with a GI bleed or in catabolic
patients due to steroids or sepsis. High protein tube feeds and recovery of ATN can also
lead to false positive elevations in the
BUN:Cr ratio. In some patients with pre-renal azotemia the BUN:Cr is falsely low due
to either liver failure or malnutrition. This
often is seen in alcoholics.
Fractional Excretion of sodium (FENa)
The fractional excretion of sodium is the excreted sodium divided by the amount of
sodium filtered at the glomerulus.
!
FENa
!
In pre-renal azotemia less than 1% of the
sodium is excreted. In intrinsic renal failure
more than 1% of sodium is excreted.
Calculating the FENa requires the simultaneous measurement of serum sodium and
creatinine and the urine sodium and creatinine.
FENa =
Urine Na x Sr Cr
Sr Na x Urine Cr
X 100
FENa false negatives (High FENa in Pre-renal azotemia)
The FENa is most accurate for patients who
are oliguric. The equation is inaccurate in
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Acute Renal Failure
Joel M. Topf, MD
patients who have recently received diuretics.
FENa false positives (Low FENa in ATN)
A low FENa can be found in conditions besides pre-renal azotemia. It also occurs with:
• Contrast nephropathy
• Rhabdomyolysis
• Acute GN
• Hepatorenal syndrome
• ATN with CHF
• ATN with cirrhosis
• ATN with severe burns
Remembering the FENa Equation
The FENa is a small number (especially
before you multiply it by 100. To remember the formula put all of the small numbers on the top and the big numbers on
the bottom.
FENa = small x small
big x big
Big or small?
1. Urine sodium
big
small
2. Urine creatinine
big
small
3. Serum sodium
big
small
4. Serum creatinine
big
small
The Fractional Excretion of Urea
The biggest weakness of the FENa is that it
fails in the face of diuretics. Patients who are
prone to pre-renal azotemia are often patients on diuretics. Think of CHF patients, or
oliguric patients in the hospital. So in the
very patients you would want to use the
FENa it becomes inaccurate. Enter the FE
Urea to solve this.
The equation for the FE Urea is identical to
the FENa except in everyplace there is a
sodium you replace it with urea. Instead of
1% as the line between pre-renal and intrinsic renal failure use 35%. A FE Urea less than
35% indicates pre-renal azotemia, a FE Urea
greater than 35% is indicative of intrinsic renal failure.
FE Urea =
Urine Urea x Sr Cr
Sr Urea x Urine Cr
X 100
Though the FE Urea was developed for use
in patients with previous exposure to diuretics it is just as accurate as the FENa in patients without diuretic exposure.
!
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Acute Renal Failure
Joel M. Topf, MD
Questions on Pre-renal Azotemia
Calculate the BUN:Cr ratio, FENa and FEUrea for the following patients and then interpret
each test as indicating a true positive, false positive, true negative, false negative.
58 year old white male admitted with an exacerbation of CHF. He is treated with IV diuretics and on the third hospital day the following labs are
obtained:
Serum
!
Urine
136 111
88
3.4
3.4
19
Characteristic
55
123
59
!
Value
Interpretation
BUN:Cr
FENa
FEUrea
An 82 year old nursing home resident presents to the ER with obvious dehydration. The patient has a blood pressure 80/50, is oliguric and has
cloudy, foul smelling urine in a Foley bag. The following labs are collected:
Serum
!
Urine
136 111
93
3.4
5.4
19
Characteristic
10
!
Value
123
53
Interpretation
BUN:Cr
FENa
FEUrea
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Acute Renal Failure
Joel M. Topf, MD
A 44 year old alcoholic presents to the ED with hemetemesis. On initial
labs the patient has a hemoglobin of 5 g/dL. The patient goes for emergency EGD and the bleeding is stopped. The next morning the patient has
the following labs:
Serum
!
Urine
136 111
98
3.4
3.8
19
Characteristic
62
229
22
!
Value
Interpretation
BUN:Cr
FENa
FEUrea
An elderly gentleman is shot multiple times. While planning the surgical
approach the surgeons order a contrasted CT scan. One day later the patient’s creatinine begins to rise. The patient remains non-oliguric. The
following labs are obtained:
Serum
!
Urine
136 111
64
3.4
3.4
Characteristic
19
Value
!
12
N/A
67
Interpretation
BUN:Cr
FENa
FEUrea
N/A
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Acute Renal Failure
Joel M. Topf, MD
Post-renal insufficiency
When the plumbing is clogged the kidneys fail.
Post-renal AKI is immediately intuitive.
When the urinary tract is blocked renal function falls. One of the most important aspects
to understand is how unilateral obstruction
placed after the patient attempts to urinate
and the post-void residual is recorded.
Post-Void Residual
< 50 mL................normal
Urinary obstruction review of systems:
Do you have nocturia? Has it changed?
Has the strength of your stream decreased?
Do you have double voiding?
Urinary frequency?
Hesitancy?
Do you need to strain (valsalva) to urinate?
100 mL .................Normal over 65
> 200 mL ..............very abnormal
Ultrasound is the “gold-standard” for the
diagnosis of obstructive uropathy.
Ultrasound is quick, non-invasive and painless. It is also highly sensitive and specific
for the correct diagnosis. Unfortunately there
Do you have urinary incontinence or dribbling?
works. In patients with two functioning kidneys, blocking a single kidney will not cause
renal failure. Renal failure requires either bilateral obstruction or unilateral obstruction
in a patient with a single functioning kidney.
The most common cause of bilateral obstruction in males is prostatic hypertrophy. In
women it is cervical cancer. When people
think of obstruction it is easy to solely think
of physical obstruction but a neurogenic
bladder from neurologic disease (MS) metabolic derangements (diabetic neuropathy) or
drugs can be occult sources of obstruction.
Urine output is usually, but not always, decreased in obstructive uropathy. In some patients the primary symptom of obstruction is
nocturia. Anuria is highly suggestive of bilateral obstruction.
The diagnosis can almost always be made
with a combination of a renal ultrasound
and Foley’s Catheter. Make sure the Foley is
a few situations where the ultrasound can
give a false negative result (i.e. a normal renal ultrasound in the presence of clinically
significant obstruction):
1. Concurrent volume depletion and obstructed may not show hydronephrosis on the ultrasound until after fluid
resuscitation.
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Acute Renal Failure
2. Patients early in the course of obstruction may not have developed hydronephrosis yet.
3. Large retroperitoneal tumors can encase the kidney and both cause the
obstruction and prevent hydronephrosis.
Joel M. Topf, MD
Treating Post Renal AKI
Treatment of post-renal acute renal failure is
usually simple once the diagnosis has been
made. Patients with neurogenic bladder will
have brisk recovery after a Foley is placed.
4. Retroperitoneal fibrosis (idiopathic or
post-radiation therapy) can prevent
hydronephrosis.
Also be careful of false positives. A dilated
collecting system is a normal finding in
pregnancy. Bladder scans can falsely report
high residual bladder volume in patients
with abdominal ascites.
One last finding which can suggest obstructive uropathy is: hyperkalemia out of proportion to the degree of renal failure. Often
patients with obstructive uropathy will have
severe hyperkalemia with mild to modest
renal failure.
Physical Obstruction
• Phimosis
• Stricture
• Prostatitis
• Trauma
• Blood clot
• Stone
• BPH
• Prostate / bladder cancer
• Cervical cancer
• Colon cancer
• Sarcoidosis
• Tuberculosis
• Pregnant Uterus
Involve urology for more complex mechanical obstruction. Interventional radiology
may be helpful by placing percutaneous
nephrostomy tubes in patients with recalcitrant obstruction.
Neurogenic Bladder
• Diabetes mellitus
• Spinal cord disease
• Multiple Sclerosis
• Parkinsons disease
• Anticholinergic drugs
• diphenhydramine
• Alpha-adrenergic agonists
• ephedrine
• pseudoephedrine
• Calcium channel blockers
• Opiates
• Sedative hypnotics
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Acute Renal Failure
Joel M. Topf, MD
Questions on Post-Renal AKI
A 58 year old white female is admitted on a Friday evening from her Gyn’s office with a diagnosis of vaginal bleeding. Initial labs show:
Serum
136 111
44
7.8
2.8
16
What is the likely diagnosis? What problems need to be addressed immediately?
A 78 year old white male with a history of mild prostatism has been self treating for a “sinusitis” for the last few days with over the counter medications.
He finally relents and comes to the doctor for “some antibiotics.” The PCP orders routine labs and sends him home. The patient receives a call that evening
telling him to go straight to the ED. The initial labs are to the right:
What’s going on?
Serum
143 111
68
5.4
4.9
17
A 32 year old returns to the ED because the pain from his previously diagnosed kidney stone has gotten much worse and he has developed nausea and
vomiting. A CT scan from earlier in the week revealed a 3 mm stone in the distal ureter and a 12 mm stone in the left renal pelvis. Before you arrive the ER
gets a stat U/S which shows hydronephrosis on the left.
!
Serum
Urine
136 111
52
4.8
3.6
22
!
31
156
29
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Acute Renal Failure
Joel M. Topf, MD
Intrarenal acute renal failure
Intrinsic acute renal failure comes in a number of flavors but this guide will only examine diagnosis and three specific etiologies: ischemic ATN, contrast nephropathy and interstitial
nephritis.
Intrinsic acute renal failure is the most comThe concentrated urine is seen in pre-renal
mon cause of acute renal failure among hosconditions. False positives are found in papitalized patients. Unlike pre- and post- retients with ATN in the background of CHF
nal failure there is typically no direct and
and cirrhosis and with pigmented nephropaeasy therapy. The role of the physician is relthy or acutely following contrast administraegated to supportive care as she waits for the
tion.
kidneys to recover on their own. However
The isothenic urine is seen with non-oliguric
the condition is quite severe with a high
ATN (including recovery of ATN) and adhospital mortality. Among all hospitalized
vanced CKD, including dialysis patients.
patients it is usually around 30%. For septic
Damaged tubules are unable to concentrate
patients in the ICU it can be as high as 70%
or dilute the urine. The tubules are on strike.
hospital mortality.
Protein: Proteinuria is characteristic of just
Even survivors are not entirely off the hook.
about any glomerular damage, from diabetes
The development of AKI is a large risk facto lupus nephritis. The finding of proteinuria
tor, and even may cause chronic kidney disis difficult to interpret because it is impossiease (CKD). Patients who survive AKI need
ble to differentiate if it is pre-existing disease
regular follow-up and screening for CKD.
or associated with the AKI. The absence of
proteinuria effectively rules out glomerulonephritis.
Diagnosis
The art of the Urinalysis
The cheapest objective test available is the
urinalysis. It is a liquid biopsy of the kidney
and can be quite informative. Don’t forget to
order the U/A! Don’t be the tool who orders
a FENa, FEUrea, renal ultrasound, but forgets the U/A.
The urinalysis is a two part analysis: a biochemical profile followed by a microscopic
exam.
Biochemical assessment
Specific gravity: look for two extremes: the
concentrated urine with specific gravity
greater than 1.020 and the dilute isothenic
urine (1.010).
Hematuria is assessed in both components
of the urinalysis. In the biochemical assessment, the assay measures heme and interprets this as blood. This will have false positives from myoglobulinuria from rhabdomyolysis or from hemoglobinuria associated with hemolysis. The biochemical assessment does not differentiate glomerular
blood from lower tract blood. Glomerular
blood and AKI are associated with acute
GN, interstitial nephritis. Positive heme
without RBC on microscopy indicates rhabdomyolysis or hemolysis.
Microscopic analysis
The microscopic analysis can identify a few
enormously helpful findings:
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Acute Renal Failure
Dirty brown casts are pathognomonic for
ATN. It is composed of dead tubular epithelial cells.
Joel M. Topf, MD
Hyaline casts are a normal finding. They are
prominent in acidic urine as found with:
loop diuretics and concentrated urine (first
morning urine). Also found following vigorous exercise.
Red cell casts are pathognomonic for
glomerulonephritis and usually trigger a
kidney biopsy.
Red blood cells. Found with glomerular
disease, tubular disease, foley specimens,
cystitis. Nonspecific finding that, like proteinuria, is more valuable when it is negative
to rule out most types of kidney injury.
Oval fat bodies: indicative of lipiduria
found with nephrotic syndrome.
Broad waxy casts are indicative of chronic
kidney disease.
Bacteria useful in the diagnosis of cystitis
and pyelonephritis.
WBC casts: found with pyelonephritis and
acute interstitial nephritis.
Clinical Syndromes
There are two non-specific syndromes which
are used to classify glomerular disease.
These can usually be identified by the history and physical and the U/A.
Nephrotic syndrome: A non inflammatory
glomerular injury with massive proteinuria
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Acute Renal Failure
Joel M. Topf, MD
(proteinuria > 10x the upper limit of
normal). Patients are edematous but typically have normal blood pressure. Rarely associated with AKI.
proteinuria (though not as much as with
nephrotic syndrome) RBC casts (variable).
Clinically the patients have renal failure and
hypertension. This is an important cause of
AKI.
Nephritic syndrome: An inflammatory
glomerular injury. Patients have hematuria,
Questions on the Urinalysis
Match the U/A to the patient to the diagnosis
U/A 1
U/A 2
U/A 3
U/A 4
U/A 5
U/A 6
1.020
1.010
1.014
1.010
1.012
1.040
Protein
neg
2+
3+
4+
1+
neg
Heme
neg
neg
3+
1+
2+
neg
Micro
hyaline
casts
waxy casts
RBC Casts
SpGrav
oval fat
bodies
WBC casts
nothing
Patient
Dx
Patients
A. 26 y.o. AA female with rash, joint pain, anemia and a Cr of 3.4.
B. 64 y.o. white male who had a cardiac cath 6 hours ago.
C. 40 y.o. white female with a diabetic foot ulcer. She is on cefazolin for osteomyelitis She develops a fever, rash and AKI.
D. 38 y.o. with alcoholic cardiomyopathy. Patient is admitted for CHF. He develops hospital
acquired AKI on hospital day 3.
E. 37 y.o. black female with AIDS. She is poorly compliant with her HAART regimen and
presents with lower extremity edema.
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Acute Renal Failure
Joel M. Topf, MD
F. 62 y.o. white male with a 20 year history of diabetes, a Cr of 2.8 mg/dl and a 15 year history of proteinuria.
Diagnosis
1. Collapsing focal segmental glomerulosclerosis (FSGS)
2. Contrast exposure
3. Pre-renal azotemia
4. Acute interstitial nephritis
5. Lupus nephritis
6. Chronic kidney disease
Ischemic acute tubular necrosis
Disruptions in blood supply to the kidney cause acute renal failure.
The kidneys normally receive a rich blood
Any insult that causes a de- crease in blood
supply. In fact 20% of cardiac output, 1 liter
pressure can cause ATN. Bleeding, sepsis,
per minute, is devoted to perfusing the kidsevere volume depletion, ACEi and NSAIDs
neys. Despite this abundance of perfusion,
all can cause ATN. ATN will cause oliguria
almost all of this blood goes solely to the rein about 70% of cases. The remainder will be
nal cortex leaving the deep medullary tissue
non-oliguric. Patients will remain in renal
relatively devoid of oxygen. Much of the
failure usually for 4-14 days, though longer
medulla lives in continuous ischemia at the
courses may occur. Loop diuretics can be
very margin of viability. Brief interruptions
used to increase urine output but they fail to
of perfusion can push these marginal tissues
shorten the duration of dialysis. Patients
(the cells that line the renal tubules) into
who do not have a good response to IV dioxygen debt and cause them to die and
uretics have a much worse prognosis than
slough into the urine. Once perfusion rethose with a good diuretic response.
sumes the tissue regenerates and the kidney
function is restored.
Toxic acute renal failure
A number of nephrotoxins can cause acute renal failure
The very high renal blood flow means that
• Acute interstitial nephritis
the kidney is exposed to many toxins. These
• crystallization in the renal tubules
can disrupt normal renal function and cause
• antagonize proximal tubule creatinine
acute renal failure.
secretion.
Vancomycin and the aminoglycosides are
Nephrotoxins often work in concert with
famously nephrotoxic. Some agents like
other renal insults such as dehydration to
trimethoprim sulfamethoxazole can cause
multiple types of renal failure:
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Acute Renal Failure
Joel M. Topf, MD
increase toxicity. One of the most worrisome
nephrotoxins is iodinated contrast.
Contrast Nephropathy
You were just trying to make a diagnosis and you boxed the kidneys.
Iodinated contrast agents are responsible for
• Avoid using contrast when imaging the
12-14% of hospital acquired acute renal failpatient. Make sure the contrast is absoure. Patients with pre-existing chronic kidlutely needed. Assessing an aortic
ney disease and diabetes are at the highest
aneurism? No need for contrast. Looking
risk for this complication.
for a retroperitoneal hematoma? No need
for contrast. Kidney stone? No contrast.
Contrast nephropathy is usually defined as a
Oral contrast is safe. Angiograms can
0.5 mg/dL or 25% increase in serum creatisometimes be done with CO2 rather than
nine within 48 hours of administration of
iodinated contrast agents.
contrast. The creatinine usually starts rising
immediately after contrast is given and
peaks on day 4. Typically, the creatinine remains above baseline 10 days after contrast
administration. The acute renal failure is
typically non-oliguric and has a low FENa.
People with contrast nephropathy have poor
prognosis. The rise in hospital mortality occurs even when patients do not require dialysis. In patients with the need for dialysis
the condition becomes truly devastating.
Mortality
62%
34%
31%
• Use isoosmolar or low osmolar contrast
agents. Some contrasts are more nephrotoxic than others. These two are the
safest.
• Minimize the dose of contrast. If the patient is going for a left heart catheterization, get the echo first so there is no need
for a ventriculogram to asses cardiac
function
• Make sure the patient is not volume depleted. IV saline is the most effective
weapon to reduce contrast nephropathy.
0.9 NS is more effective than 0.45 NS. To
maximize the benefit give as much hydration as the patient can tolerate.
• Stop drugs associated with increased
risk of contrast nephropathy:
7%
CN, +HD
CN
CN, no HD
!
No CN
• Diuretics
There are some precautions one can take to
reduce the risk of contrast nephropathy:
• Mannitol
• ACEi/ARB
• NSAIDs.
• N-acetyl cysteine and sodium bicarbonate are no better than placebo and normal saline respectively.
!20
Acute Renal Failure
Joel M. Topf, MD
Acute Interstitial Nephritis
A drug induced allergic reaction that takes the
kidneys down.
In most cases, the cause of acute renal failure
is obvious:
• The patient received contrast
• Patient develops hypotension
• The patient passes a liter and a half of
urine after someone thinks to place a Foley
• Creatinine falls after a night of IV fluids
Then there are the exceptions, the patients
whose renal function declines day after day
with no obvious source of renal failure. They
don’t respond to IV fluids. The patient
Most common drugs associated with
AIN
• NSAIDs
• Selective COX-2 inhibitors
• Penicillins
• Cephalosporins
• Rifampin
• Sulfonamides (Bactrim)
• Furosemide, bumetanide
• Thiazide-type diuretics
• Ciprofloxacin and other quinolones
• Cimetidine
• Allopurinol
• Omeprazole and lansoprazole
• Indinavir
• Mesalamine
!21
Acute Renal Failure
doesn’t have a history of contrast exposure,
no gentamicin on the MAR. These are the
cases where a cagey nephrologist is needed.
The differential diagnosis of occult AKI is
long and complex and beyond the scope of
this workshop. One etiology I would like to
highlight is acute interstitial nephritis (AIN).
AIN is an allergic reaction, typically to a
drug which results in acute renal failure. Patients need prolonged exposure to the drug
to develop their first case of AIN but the renal failure can recur within days on subsequent exposures to the drug.
Joel M. Topf, MD
The classic presentation is renal failure in the
presence of hematuria, pyuria, fever and
rash. The patients are almost always nonoliguric and serum potassium tends to be
low rather than high.
The classic drug-class responsible for AIN is
ß-lactam antibiotics but the list of drugs associated with AIN is long and varied (see
box).
Therapy focuses on stopping the offending
drug. Some retrospective data suggests that
high dose steroids are beneficial. The
steroids should be used early to be most effective. (Gonzalez E, Et al. Kidney International (2008) 73, 940–946)
!22
Acute Renal Failure
Joel M. Topf, MD
Hyperkalemia
One of the most concerning causes of morbidity with AKI is hyperkalemia. Hyperkalemia is a particular problem with obstructive uropathy, tumor lysis syndrome and
rhabdomyolysis.
Hyperkalemia can occur from three primary
sources:
1. Increased intake. This can be either enteral through potassium supplements
and diet or enteral as found in potassium
infusions, blood transfusions and TPN.
2. Movement of potassium from inside cells
to the outside of cells. The concentration
of potassium inside cells is about 140
mEq/L so tissue death releases a tremendous amount of potassium. This occurs
in tumor lysis syndrome, crush injuries,
and rhabdomyolysis.
3. Inability of the kidneys to excrete potassium. This could be due to generalized
renal failure or a specific inability to excrete potassium. The later occurs with
medications, diabetes, or obstructive
uropathy.
In general the first two causes result in transient hyperkalemia, as healthy kidneys are
able to up-regulate clearance of potassium
and excrete almost any dietary or endogenous load. Persistent, clinically significant
hyperkalemia always has at least a component of excretion failure.
Drug induced hyperkalemia
• ACEi
• ARB
• Aldosterone antagonists
• Digoxin
• Beta-blockers
• Heparin
• Triamterene
• Amiloride
• Trimethoprim
• Potassium supplements
• Ringer’s solution
• Penicillin G
• Amicar
• Succinylcholine
• NSAID
• Pentamidine
• Cyclosporine
• Tarolimus
!23
Acute Renal Failure
Joel M. Topf, MD
EKG Changes with hyperkalemia
Normal EKG
Initial finding is
peaked T waves
Widening of the QRS
complex and shortened
ST interval
A sinusoidal EKG
Treating hyperkalemia.
Treatment of hyperkalemia follows the same conceptual framework as the differential diagnosis: intake, distribution and excretion.
The treatment of hyperkalemia needs to be
fastidious and follow-up is critical. Patients
with potassiums greater than 6 mmol/L
should have an EKG to look for typical EKG
changes. Patients with these changes should
be given calcium to stabilize the cardiac
membranes.
Hyperkalemia orders
• Stop all sources of potassium
• Stat EKG
• Consider transfer to telemetry
• Calcium gluconate 1g IVPB or IVP
• Calcium chloride 1g IVPB or IVP in
patients with central access
• Insulin 10 units IVP (note not subQ)
followed by 1 amp of D50 IVP follow serial blood glucose to avoid
hypo- and hyperglycemia
• Calcium chloride if the patient have central access
• Calcium gluconate if they only have peripheral access
This can be repeated every 5 minutes in order to correct EKG changes. Calcium should
• Albuterol 10-20 mg by nebulizer
• Sodium polystyrene 15-30g po
• avoid if sick GI tract
• Furosemide IV and saline. Use
twenty times the serum creatinine
as the dose in mg (max. 80 mg)
• Call or consult nephrology
• Assess and correct any causes of
hyperkalemia
!24
Acute Renal Failure
Joel M. Topf, MD
be used with caution in cases of digoxin toxicity.
0.0
0
Intake
15
30
45
60
To start lowering the potassium stop any
source of additional potassium. Review all of
the medications and make sure all IVs are
potassium free. Stop TPN.
Change in K
-0.3
-0.6
-0.9
Transcellular shift
This is the mainstay of acute management of
hyperkalemia. Beta-agonists (albuterol) and
insulin are the primary drugs which shift
potassium into cells. These drugs stimulate
the Na-K-ATPase and can lower the potassium by about 1 mEq/L in about in an hour.
Sodium bicarbonate is sometimes used to
lower the potassium. Multiple studies have
shown that this is ineffective and there are
theoretical concerns that it maybe harmful.
A banana has
about one mEq of
potassium per inch.
-1.2
-1.5
Time (min)
Insulin
Albuterol
Combination
Excretion from the body
Final correction of hyperkalemia requires
getting rid of excess potassium either
through the GI tract or via the kidneys. In
patients with functioning kidneys, a dose or
two of furosemide along with a generous
dollop of saline is usually enough to correct
the hyperkalemia. In patients with severe
chronic kidney disease or on dialysis use of a
cation exchange resin like Kayexylate is required to use the GI tract to excrete excess
potassium. If hyperkalemia occurs in a dialysis patient the nephrologist needs to be notified so a prompt decision regarding dialysis can be made.
Question on hyperkalemia
A 71 year old Asian man presents with acute renal failure due to
dehydration. Initial labs show a potassium of 6.7. The EKG shows a
QRS complex of 123 msec. A Previous EKG showed a QRS of 110
msec.
!25
Acute Renal Failure
How would you handle
Joel M. Topf, MD
this situation?
Answers
KDIGO 1
KDIGO stage 3
Obstruction due to cervical Ca, Address hyperkalemia
Obstruction due to OTC cold medicine on top of BPH
KDIGO stage 2
KDIGO stage 2
KDIGO stage 3
Question: Elderly with more pre-renal azotemia? Increased
CKD decreases the ability to concentrate urine predisposing to fluid loss. Co-morbidities require diuretics
Why do they have more post-renal failure? Increased BPH,
increased risk of Cx Ca.
BUN:Cr 14.4, FENa 2.8%, FEUrea 37%, ATN due to
NSAIDS, obstruction is not the cause b/c it is unilateral.
Questions on urinalysis
U/A 1: patient D, diagnosis 3
U/A 2: patient F, diagnosis 6
U/A 3: Patient A, diagnosis 5
U/A 4: Patient E, diagnosis 1
U/A 5: Patient C, diagnosis 4
U/A 6: Patient B, diagnosis 2
Question: What drugs antagonize afferent vasodilation?
NSAIDS
Efferent Vasoconstriction? ACEi & ARB
Remember the FENa Eq.
small, big, big, small
BUN:Cr 25.9, FENa 2.2%, FEUrea 8%, use of diuretics causes the false (–) FENa
BUN:Cr 17.2, FENa 0.7%, FEUrea 13%, malnutrition
causes false (–) BUN:Cr
BUN:Cr 25.8, FENa 7.9%, FEUrea 40%, GI bleed
causes false (+) BUN:Cr
BUN:Cr 18.8, FENa 0.4%, false (+) FENa due to contrast
!26