Acute Renal Failure:

a Practical Workshop

Joel M. Topf,MD
Clinical Nephrologist
Cell 248.470.8163
Office 313.886.8787
http://pbfluids.blogspot.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 at-
oms in order to nudge the patient toward recovery.

Goals
• Invention of dialysis • FEUrea
• Definition of ARF • Post-renal
• RIFLE Criteria • Intrinsic Acute Renal Failure
• AKIN Criteria • U/A
• Etiologies of inpatient versus • ATN
outpatient acute renal failure. • Contrast nephropathy
• Pre-renal azotemia • AIN
• BUN:Cr ratio
• FENa

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Acute Renal Failure Joel M. Topf, MD
Table of Contents
History of acute renal failure therapy .......................................... 4

Definition of ARF ............................................................................ 5

Rifle Criteria ..................................................................................... 5

AKIN Criteria ................................................................................... 6

Classify the following using the RIFLE Criteria ......................... 7

Differential Diagnosis ..................................................................... 8

Pre-renal azotemia ........................................................................... 9

Diagnosing Pre-renal ...................................................................... 9

Treating Pre-renal azotemia ........................................................... 12

Post-renal insufficiency .................................................................. 15

Treating Post Renal ARF ................................................................. 16

Questions on Post-Renal ARF ........................................................17

Intrarenal acute renal failure ..........................................................18

Diagnosis .......................................................................................... 18
Clinical Syndromes ..........................................................................21

Questions on the Urinalysis ........................................................... 22

Ischemic acute tubular necrosis ..................................................... 23

Contrast Nephropathy ....................................................................24

Acute Interstitial Nephritis ............................................................ 26

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Acute Renal Failure Joel M. Topf, MD
History of acute renal failure therapy

Dr. Haas in his laboratory with the first human dialysis machine in 1928.
Extracorporeal dialysis for humans was first tested in the 20’s by Dr.
Haas. He treated 6 patients, all of which 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 ne-
phritis 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?
A. 5
B. 10
C. 15
D. >20

4
Acute Renal Failure Joel M. Topf, MD
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 ther-
apy. This was his 17th patient after 16 consecutive treatment failures. She
lived another 8 years and ultimately died of community acquired pneu-
monia.

the Acute Dialysis Quality Initia-

Definition of ARF tive, this validated definition of
The study of ARF has been ham- ARF is called the RIFLE Criteria.
pered by a proliferation of defini- The second was developed by the
tions for ARF. Acute Kidney Injury Network
(AKIN) and is a minor modifica-
The classic text-book definition
tion of the RIFLE criteria called the
of acute renal failure is “An acute
AKIN Criteria.
and sustained decrease in renal func-
tion.” Unfortunately this accepted Rifle Criteria
definition is hampered by ambigu-
Numerous studies have vali-
ity: How acute? How sustained?
dated these criteria showing
How should renal function be
graded increases in hospital mor-
measured? Is the degree of renal
tality and morbidity with increas-
impairment important?
ing degrees of renal failure as de-
As clinical scientists studied fined by the RIFLE Criteria:
ARF they needed specific case-
A university hospital in Aus-
definitions of ARF and each re-
tralia1 looked at all admissions and
searcher created their own. At last
found a stepwise increase in hospi-
count there were over 35 separate
tal mortality as patients progressed
definitions of ARF. This created
through Risk, Injury and Failure.
chaos where one study couldn’t be
Importantly Failure had the same
compared to another and has
mortality regardless if it came from
hampered progress in the field of
a tripling of Cr or Cr > 4.
ARF.
The University of Pittsburgh2
Recently, two, related, defini-
found a similar step wise increase
tions have gained consensus accep-
in mortality when they looked at
tance. The first was developed by
their ICU patients.

5
Acute Renal Failure Joel M. Topf, MD
RIFLE Criteria Change Oliguria Hospital AKIN
in Cr mortality Criteria

1.5-2.0 < 0.5 mL/kg/ Stage 1 (in-

23%1
Risk X base- hr for more crease in Cr
8.8%2
line than 6 hrs 0.3 mg/dL)

< 0.5 mL/kg/

2-3 X 44%1
Injury hr for more Stage 2
baseline 11.4%2
than 12 hrs

over 3 X < 0.3 mL/kg/ Stage 3 (in-

baseline hr > 24 hrs 52%1 cludes any
Failure
or Cr > or anuria 26.3%2 patient who
4 mg/dL for > 12 hrs receives RRT)

Loss of func- Need for dialysis for more than 4

tion weeks

End-Stage Need for dialysis for more than 3

Renal Disease months
1 Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.
2 Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

AKIN Criteria Loss and End Stage and only

These newer criteria come
from a different consensus group
and really respond to two criti-
cisms of the RIFLE criteria:
1st is that the last two cri-
teria, loss of function
and end-stage renal disease, are
actually outcomes, not measures
of severity of renal injury. Re-
searchers that have validated the
RIFLE criteria actually ignored
validated the first three criteria.
The AKIN criteria only divide
patients based on severity of
illness and do not grade patients
based on duration of debility.
The second criticism is
2nd that there is docu-
mented harm associated with
smaller degrees of renal failure
than are recognized with Risk.
Changes of creatinine as low as
0.3 mg/dL have been associated
with poor outcomes. The AKIN
6
Acute Renal Failure




Joel M. Topf, MD
criteria lower the threshold to sensitivity of the definition.
this low limit to maximize the

Classify the following using the RIFLE Criteria

A 32 year old African American hair model with a baseline creati-

nine 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 acci-

dent. He goes for emergency splenectomy and repair of a liver
laceration. Despite aggressive use of blood products and crystal-
loids he has been anuric since a foley was placed 14 hours ago.

A 62 year old model for a national nursing home chain has arthri-
tis 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 tid,
chlorthalidone 25 mg qd, simvastatin 40 mg qd and ramipril 10
mg qd. Her labs show a Cr of 3.2 (baseline 1.2), K of 6.6. 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.

An 82 y.o. nursing home resident with diabetic nephropathy falls.

On exam he has an S3, rales and pitting edema. 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 azo-
temia (obstructive uropathy).
Using these categories one is Another clue to the etiology
able to quickly narrow the differen- can be the age of the patient. Pas-
tial diagnosis of acute renal failure cual, et al. showed that as patients
and determine the likely natural age post-renal etiologies and pre-
history of the condition. Pre- and renal etiologies of ARF become
post- renal ARF usually are quickly more common at the expense of
reversible and easy to treat. They decreasing intrarenal causes.
are often obvious from the history.
When the etiology of ARF is 100%
not obvious it is helpful to be 17% 12% 11%
75% 7% 11% 20%
aware of the incidence of the eti-
ologies in various clinical settings. 50% 48%
56% 39%
Multiple studies have shown that
patients with ARF upon presenta- 25%
tion to the hospital have different 20% 29% 30%
0%
causes of ARF than patients who
<65 65-79 >79
develop ARF while in the hospital.
Prerenal Intrarenal
4% Postrenal Unknown

38%
Question: Why might the elderly have
58% more pre-renal azotemia?
Why do they have more
post-renal failure?
17%
Hospital acquired
ARF 11%

72%
Prerenal
Intrarenal Outpatient acquired
8
Postrenal ARF
 Acute Renal Failure




Joel M. Topf, MD
Pre-renal azotemia
No BP; No pee pee. nine doesn’t rise and the patient is
not pre-renal. They are pre-pre-renal.
Volume depletion from any
etiology decreases renal perfusion. Question: What drugs antagonize
The decrease in renal plasma flow afferent vasodilation? Efferent Vaso-
(RPF), if uncompensated will de- constriction?
crease GFR. We call a decrease in Diagnosing Pre-renal
GFR, azotemia.
There are three tests you need to be
Heart failure and cirrhotic pa- facile with to separate pre-renal
tients are both edematous. These azotemia from intrinsic AKI: the
patients have total body sodium BUN:Cr ratio, the fractional excre-
excess but the amount of fluid in tion of sodium and the fractional
the arterial excretion of urea.
Doc, I’ve had diarrhea blood compart-
and vomiting for the In volume depletion the kid-
ment, the effec-
last three days and can’t neys become sodium avid and re-
keep a thing down. tive circulating
volume, is de- tain BUN out of proportion to cre-
creased. This atinine. This allows physicians to
results in pre-renal azotemia de- make quantitative assessments of
spite the overloaded appearance. volume depletion and make an
accurate diagnosis.
As RPF falls the kidney com-
pensates to maintain a stable GFR. BUN:Cr ratio
There are two primary strategies
for this:
Vasodilation of the affer-
1st ent arteriole via local PGE AT2
prostaglandin production.
Efferent vasoconstriction
2nd via angiotensin II.
These strategies increase intra-
glomerular pressure to maintain
GFR despite a fall in RPF; a higher
percentage of plasma is filtered. If
these strategies are successful, the GFR
Filtration fraction =
GFR remains constant, the creati- RPF
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Acute Renal Failure
Joel M. Topf, MD
A BUN to Cr ratio over twenty
is a reasonably accurate indicator
of volume depletion. It works be-
cause the BUN:Cr ratio actually
measures the filtration fraction at
the glomerulus.
The increased filtration fraction
means that the plasma proteins
that are not filtered by the glom-
erulus are diluted in less plasma
(because more of that plasma went
down the glomerular drain). This
higher concentration of plasma
proteins exert greater osmotic at-
traction in the proximal tubules
bringing back more plasma water,
sodium and urea. Creatinine is ac-
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 pro-
tein tube feeds and recovery of
ATN can also lead to false positive
elevations in the BUN:Cr ratio. In
some patients with pre-renal azo-
temia the BUN:Cr is falsely low
due to either liver failure or malnu-
trition. This often is seen in alco-
holics.
Fractional Excretion of sodium
(FENa)
The fractional excretion of so-
dium is the excreted sodium di-
vided by the amount of sodium
filtered at the glomerulus. In pre-
renal azotemia less than 1% of the
sodium is excreted. In intrinsic re-
nal failure more than 1% of sodium
is excreted.

tively secreted in the proximal tu-

bule and is not affected by this os-
motic movement of water. The net
result is normal creatinine clear-
ance and decreased urea clearance
resulting in a rise in BUN out of
proportion to the rise in creatinine.
The BUN:Cr calculation is easy
to remember, doesn’t require a cal-
culator and is surprisingly accu-
rate; however the test has some

10
Acute Renal Failure Joel M. Topf, MD
FENa false negatives (High FENa
in Pre-renal azotemia)
The FENa is most accurate for
FENa patients who are oliguric. The
equation cannot be used in patients
who have recently received diuret-
ics.
FENa false positives (Low FENa in
ATN)
Urine Na x Sr Cr
FENa = X 100 A low FENa can be found in
Sr Na x Urine Cr conditions besides pre-renal azo-
temia. It also occurs with:
Calculating the FENa requires the • Contrast nephropathy
simultaneous measurement of se- • Rhabdomyolysis
rum sodium and creatinine and the • Acute GN
urine sodium and creatinine. • 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.
small x small
FENa =
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

11
Acute Renal Failure Joel M. Topf, MD
The Fractional Excretion of Urea 35% is indicative of intrinsic renal
failure.
The biggest weakness of the
FENa is that it fails in the face of Though the FE Urea was de-
diuretics. Patients who are prone to veloped for use in patients with
pre-renal azotemia are often pa-
tients on diuretics. Think of CHF
patients, or oliguric patients in the Urine Urea x Sr Cr
hospital. So in the very patients FE Urea = X 100
Sr Urea x Urine Cr
you would want to use the FENa it
becomes inaccurate. Enter the FE
Urea to solve this. previous exposure to diuretics it is
The equation for the FE Urea is just as accurate as the FENa in pa-
identical to the FENa except in eve- tients without diuretic exposure.
ryplace there is sodium you replace (Carvounis, Sabeeha, Nisar, Et al.
it with urea. Instead of 1% as the Kidney Int, 2002 Vol 62. p 2223-
line between pre-renal and intrinsic 2229)
renal failure, use 35%. A FE Urea
less than 35% indicates pre-renal
azotemia, a FE Urea greater than

Treating Pre-renal azotemia

The kidneys are thirsty, give them a drink of water.
In pre-renal azotemia, nor- depleted, IV replacement will fix
mally functioning kidneys are re- the problem. In patients with clini-
sponding normally to volume de- cal hypervolemia and biochemical
pletion. This is not pathology; it is evidence of pre-renal azotemia the
physiology. If the patient is volume therapy is more nuanced.

12
Acute Renal Failure Joel M. Topf, MD
Calculate the BUN:Cr ratio, FE Na and FE Urea 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 fol-
lowing labs are obtained:
Serum Urine

136 111 88 55 123

3.4 19 3.4 59

Characteristic 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 10 123

3.4 19 5.4 53

Characteristic Value Interpretation

BUN:Cr

FENa

FEUrea
13
Acute Renal Failure Joel M. Topf, MD
A 44 year old alcoholic presents to the ED with hematemesis. 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 62 229

3.4 19 3.8 22

Characteristic 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 re-
mains non-oliguric. The following labs are obtained:
Serum Urine

136 111 64 12 N/A

3.4
19 3.4 67

Characteristic Value 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 ARF is immediately of a renal ultrasound and Foley’s
intuitive. When the urinary tract is Catheter. Make sure the Foley is
blocked renal function falls. One of placed after the patient attempts to
the most important aspects to un- urinate and the post-void residual
derstand is how unilateral obstruc- is recorded.
tion works. In
“Doctor, I have a hard patients with
time initiating a stream
two function- Post-Void Residual
and it only comes out like
ing kidneys, < 50 mL............. normal
a trickle.”
blocking a sin- 100 mL.............. likely abnormal
gle kidney will not cause renal > 200 mL........... very abnormal
failure. Renal failure requires either
bilateral obstruction or unilateral Ultrasound is considered the
obstruction in a patient with a sin- “gold-standard” for the diagnosis
gle functioning kidney. of obstructive uropathy.
The most common cause of Ultrasound is quick, non-
bilateral obstruction in males is invasive and painless. It is also
prostatic hypertrophy. In women it highly sensitive and specific for the
is cervical cancer. When people correct diagnosis. Unfortunately
think of obstruction it is easy to there a few situations where the
solely think of physical obstruction
but a neurogenic bladder from
neurologic disease (MS), metabolic
derangements (diabetic neuropa-
thy), 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 sugges-
tive of bilateral obstruction.
The diagnosis can almost al- ultrasound can give a false nega-
ways be made with a combination tive result (i.e. a normal renal ultra-

15
Acute Renal Failure Joel M. Topf, MD
sound in the presence of clinically hyperkalemia out of proportion to
significant obstruction): the degree of renal failure. Often
patients with obstructive uropathy
1. Concurrent volume depletion
will have severe hyperkalemia
and obstruction may not show
with mild to modest renal failure.
hydronephrosis on the ultra-
sound. Hydronephrosis may Treating Post Renal ARF
be visible following fluid re-
suscitation. Treatment of post-renal acute
renal failure is usually simple once
2. Patients early in the course of the diagnosis has been made. Pa-
obstruction may not have de- tients with neurogenic bladder will
veloped hydronephrosis yet. have brisk recovery after a Foley is
3. Large retroperitoneal tumors placed. Involve urology for more
can encase the kidney and both
cause the obstruction and pre-
vent hydronephrosis.
4. Retroperitoneal fibrosis (idio-
pathic or post-radiation ther-
apy) can prevent hydroneph-
rosis.
complex mechanical obstruction.
Also be careful of false posi- Interventional radiology may be
tives. A dilated collecting system is helpful by placing percutaneous
a normal finding in pregnancy. nephrostomy tubes in patients with
One last finding which can recalcitrant obstruction.
suggest obstructive uropathy is:

Physical Obstruction Neurogenic Bladder

• Phimosis • Diabetes mellitus
• Stricture • Spinal cord disease
• Prostatitis • Multiple Sclerosis
• Trauma • Parkinsons disease
• Blood clot • Anticholinergic drugs
• Stone • diphenhydramine
• BPH • Alpha-adrenergic agonists
• Prostate / bladder cancer • ephedrine
• Cervical cancer • pseudoephedrine
• Colon cancer • Calcium channel blockers
• Sarcoidosis • Opiates
• Tuberculosis • Sedative hypnotics
• Pregnant Uterus 16
Acute Renal Failure Joel M. Topf, MD
Questions on Post-Renal ARF

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 16 2.8

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 doc-
tor 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 below:
Serum

143 111 68
5.4 17 4.9

A 32 year old returns to the ED because the pain from his previ-
ously diagnosed kidney stone has gotten much worse and he
has developed nausea and vomiting. He has been taking OTC
pain medicine for this pain. 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 31 156

4.8 22 3.6 29

17
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 common cause of acute
renal failure among hospitalized
patients. Unlike pre- and post-renal
failure there is typically no direct
and easy therapy. The role of phy-
sicians is relegated to supportive
care as she waits for the kidneys to
heal on their own. The prognosis is
a classic good news/bad news:
Good news As patients recover
from their illness
the kidneys recover. Even among
patients that need dialysis for sup-
port during acute renal failure over
85% of survivors do not require
permanent dialysis.
Bad news If patients are sick
enough to require
dialysis, they often die. Commonly
quoted mortality for dialysis de-
pendent acute renal failure is 70%.
Some series of ICU patients with
sepsis quote a hospital mortality
rate of 80%.
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 wickedly informative. Don’t
forget to order the U/A, don’t be
“that guy” who ordered a FENa, a
FEUrea a renal ultrasound but for-
got the U/A.
The urinalysis is a two part
analysis: a biochemical profile fol-
lowed 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).
★ The concentrated urine is seen
in pre-renal conditions. False
positives are found in patients
with ATN in the background
of CHF and cirrhosis and with
pigmented nephropathy or
acutely following contrast
administration.
★ The isothenic urine is seen
with non-oliguric ATN (in-
cluding recovery of ATN) and
advanced CKD, including di-
alysis patients. Damaged tu-
bules are unable to concen-
trate or dilute the urine. The
tubules are on strike.
• Protein: Proteinuria is character-
istic of just about any glomerular
damage, from diabetes to lupus
18
Acute Renal Failure
Joel M. Topf, MD
nephritis. The finding of
proteinuria is difficult to
interpret because it is
impossible to differenti-
ate if it is pre-existing
disease or associated
with the AKI. The ab-
sence of proteinuria ef-
fectively rules out glom-
erulonephritis.
• Hematuria is assessed in
both components of the
urinalysis. In the bio-
chemical assessment, the
assay measures heme
and interprets this as
blood. This will have
false positives from my-
oglobulinuria from rhab-
domyolysis or from he-
moglobinuria associated
with hemolysis. The bio-
chemical assessment
does not differentiate
glomerular blood from
lower tract blood. Glom-
erular blood and AKI are
associated with acute
GN, interstitial nephritis.
Positive heme without
RBC on microscopy indi-
cates rhabdomyolysis or
hemolysis.
Acute Renal Success
One of the mysteries of ATN is why patients
are oliguric. If you look at a kidney biopsy of an
ATN kidney the glomerulus are completely
intact with no apparent pathology. The reason
these normal glomeruli are not filtering any
fluid may be an adaptive response to tubular
injury.
The healthy glomeruli collectively filter 100 mL
of plasma every minute. This means that all of
the plasma in the body is filtered every 30 min-
utes. Thankfully the tubules reabsorb 99% of
the filtered plasma and return it to the circula-
tion so the process can continue.
If glomerular filtering continues but tubular re-
absorption fails the kidneys would rapidly pee
the patient to death. The patient would lose a
liter of intravascular volume every 10 minutes.
To prevent this catastrophe glomerular filtration
is tightly regulated by tubular flow. At the peak
of the thick ascending limb of the loop of
Henle, as the tubule folds back to its originat-
ing glomeruli, sodium sensors regulate GFR. If
there is increased tubular sodium (indicating
an abnormally high GFR or a failure of tubular
reabsorption) then the sensors decrease GFR
by constricting the afferent arteriole. In ATN
sodium which is filtered at the glomeruli is not
reabsorbed in the proximal tubule. This results
in a flood of sodium at the peak of the TAL of
the loop of Henle. This sodium signals the af-
ferent arteriole entering the glomeruli to shut
the glomeruli down.
If the ATN is spotty this will shift blood flow to
glomeruli with intact tubules; if, however, the
ATN is more generalized then this will globally
decrease GFR resulting in oliguria.
This adaptive, tubular-glomerular feedback
explains why patients are oliguric with ATN.
19
Acute Renal Failure




Joel M. Topf, MD
Microscopic analysis • WBC casts: found with pye-
lonephritis and acute interstitial
The microscopic analysis can iden-
nephritis.
tify a few enormously helpful find-
ings:
• Dirty brown casts are pathog-
nomonic for ATN. It is com-
posed of dead tubular epithelial
cells.

• Hyaline casts are a normal find-

ing. They are prominent in acidic
urine as found with: loop diuret-
ics and concentrated urine (first
morning urine). Also found fol-
lowing vigorous exercise.
• Red cell casts are pathogno-
monic for glomerulonephritis
and usually trigger a kidney bi-
opsy.

• Red blood cells. Found with

glomerular disease, tubular dis-
ease, foley specimens, cystitis.
• Broad waxy casts are indicative Nonspecific finding that, like
of chronic kidney disease. 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.

20
Acute Renal Failure
Joel M. Topf, MD
• Bacteria useful in the diagnosis
of cystitis and pyelonephritis.
Clinical Syndromes
There are two non-specific syn-
dromes which are used to classify
glomerular disease. These can usu-
ally be identified by the history
and physical and the U/A.
• Nephrotic syndrome: A non in-
flammatory glomerular injury
with massive proteinuria (prote-
inuria (> 10x the upper limit of
normal). Patients are edematous
but typically have normal blood
pressure. Rarely associated with
ARF.
• Nephritic syndrome: An in-
flammatory glomerular injury.
Patients have hematuria, prote-
inuria (though not as much as
with nephrotic syndrome) RBC
casts (variable). Clinically the
patients have renal failure and
hypertension. This is an impor-
tant cause of ARF.
21
Acute Renal Failure




Joel M. Topf, MD
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

SpGrav 1.025 1.010 1.014 1.010 1.012 1.040

Protein neg 2+ 3+ 4+ 1+ 1+

Heme neg neg 3+ 1+ 2+ 1+

Micro hyaline waxy RBC oval fat WBC nothing

casts casts Casts bodies casts

Patient

Dx

Patients
A. 26 y.o. AA female with rash, joint pain, anemia and a Cr of 3.4 mg/dL.
B. 64 y.o. white male with a history of DM and CKD stage 4 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 ARF.
D. 38 y.o. with alcoholic cardiomyopathy. Patient is admitted for CHF. He
develops hospital acquired ARF 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.
F. 62 y.o. white male with a Cr of 2.8 mg/dl and 15 yr history of "protein"
on urinalysis.
Diagnosis
1. Collapsing focal segmental glomerulosclerosis (FSGS)
2. Early contrast nephropathy
3. Pre-renal azotemia
4. Acute interstitial nephritis
5. Lupus nephritis
6. Chronic kidney disease

22
Acute Renal Failure Joel M. Topf, MD
Which of the U/As is nephritic? Nephrotic?

Ischemic acute tubular necrosis

Disruptions in blood supply to the kidney cause a stereotypical acute re-
nal failure called ATN. This, to a large degree, is a misnomer as there is
little necrosis. A better name is acute kidney injury.
The kidneys normally receive a Any insult that causes a de-
rich blood supply. In fact 20% of crease in blood pressure can cause
cardiac output, 1 liter per minute, ATN. Bleeding, sepsis, severe vol-
is devoted to perfusing the kid- ume depletion, ACEi and NSAIDs
neys. Despite this abundance of all can cause ATN. ATN will cause
perfusion, almost all of this blood oliguria in about 70% of cases. The
goes solely to the renal cortex leav- remainder will be non-oliguric.
ing the deep medullary tissue rela- Patients will remain in renal failure
tively devoid of oxygen. Much of usually for 4-14 days, though
the medulla lives in continuous longer courses may occur. Loop
ischemia at the very margin of vi- diuretics can be used to increase
ability. Brief interruptions of perfu- urine output but they fail to
sion can push these marginal tis- shorten the duration of dialysis.
sues (the cells that line the renal Patients who do not have a good
tubules) into oxygen debt and response to IV diuretics have a
cause them to die and slough into much worse prognosis than those
the urine. Once perfusion resumes with a good diuretic response.
the tissue regenerates and the kid-
ney function is restored.

23
Acute Renal Failure Joel M. Topf, MD

Contrast Nephropathy
You were just trying to make a diagnosis and you boxed the kidneys.
Iodinated contrast agents are Contrast nephropathy is usu-
responsible for 12-14% of hospital ally defined as a 0.5 mg/dL or 25%
acquired acute renal failure. Pa- increase in serum creatinine within
tients with pre-existing chronic 48 hours of administration of con-
kidney disease and diabetes are at trast. The creatinine usually starts
the highest risk for this complica- rising immediately after contrast is
tion. given and peaks on day 4. Typi-

24
Acute Renal Failure
Joel M. Topf, MD
cally, the creatinine remains above
baseline 10 days after contrast ad-
ministration.
People with contrast nephropa-
thy have poor prognosis. The rise
in hospital mortality occurs even
when patients do not require dialy-
sis. In patients with the need for
dialysis the condition becomes
truly devastating.
Hospital Mortality
75%
50% 34% 31%
25% 7%
0%
No CN
CN
CN, no HD
Thankfully one can spare pa-
tients this complication by taking
some simple precautions:
• Avoid using contrast when imaging
the patient. Make sure the con-
trast is absolutely needed. Look-
ing for an abscess? No need for
contrast. Looking for a retroperi-
toneal hematoma? No need for
contrast. Oral contrast is safe.
Angiograms can sometimes be
done with CO2 rather than iodi-
nated contrast agents.
• 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 con-
trast nephropathy. 0.9 NS was
shown to be more effective than
0.45 NS. To maximize the benefit
give as much hydration as the
patient can tolerate.
62% • Stop drugs associated with in-
creased risk of contrast nephropa-
thy:
★ Diuretics
★ Mannitol
★ ACEi/ARB
★ NSAIDs.
CN, +HD
• Consider using N-acetyl cysteine.
Mucomyst has a checkered past.
It likely is biologically active and
is not toxic. However, there is
scant data that it prevents mor-
bidity or mortality. I use 1200 mg
BID for 2 doses before and two
doses after contrast.
• Isotonic bicarbonate after initially
showing promise has recently
failed a large high-profile trial
and may offer no benefit to pre-
venting contrast nephropathy.
The correct mixture is three
amps in a liter of sterile water or
D5W.
25
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 the renal failure can recur within
acute renal failure is obvious: days on subsequent exposures to
the drug.
• The patient received
contrast clinical characteristics of 61 biopsy proven cases of AIN.
• Patient develops hy-
potension
• 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 The classic presentation is re-
of renal failure. They don’t respond nal failure in the presence of hema-
to IV fluids. The patient doesn’t turia, pyuria, fever and rash. The
have a history of contrast exposure, patients are almost always non-
no gentamycin on the MAR. These oliguric and serum potassium
are the cases where a cagey neph- tends to be low rather than high.
rologist is needed.
The classic drug-class respon-
The differential diagnosis of sible for AIN is ß-lactam antibiotics
occult ARF is long and complex but the list of drugs associated
and beyond the scope of this work- with AIN is long and varied (see
shop. One etiology I would like to box).
highlight is acute interstitial ne-
phritis (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

26
Acute Renal Failure Joel M. Topf, MD
Therapy focuses on stopping
Most common drugs associ- the offending drug. Recent data
ated with AIN suggests that high dose steroids are
• NSAIDs beneficial. The steroids should be
used early to be most effective.
• Selective COX-2 inhibitors
(Gonzalez E, Et al. Kidney Interna-
• Penicillins
tional (2008) 73, 940–946)
• Cephalosporins
• Rifampin
• Sulfonamides (Bactrim)
• Furosemide, bumetanide
• Thiazide-type diuretics
• Ciprofloxacin and other qui-
nolones
• Cimetidine
• Allopurinol
• Omeprazole and lansoprazole
• Indinavir
• Mesalamine

27
Acute Renal Failure Joel M. Topf, MD

Answers BUN:Cr 25.9, FENa 2.2%,

FEUrea 8%, use of diuretics
causes the false (–) FENa
RIFLE: no AKI,
AKIN stage 1 BUN:Cr 17.2, FENa 0.7%,
FEUrea 13%, malnutrition
RIFLE: Failure causes false (–) BUN:Cr
AKIN stage 3

RIFLE: Injury BUN:Cr 25.8, FENa 7.9%,

FEUrea 40%, GI bleed causes
AKIN stage 2 false (+) BUN:Cr

RIFLE: Injury
AKIN stage 2
RIFLE: Failure
AKIN 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.
Question: What drugs antagonize afferent
vasodilation? NSAIDS
Efferent Vasoconstriction? ACEi & ARB
Remember the FENa Eq.
small, big, big, small
BUN:Cr 18.8, FENa 0.4%, false
(+) FENa due to contrast
Obstruction due to Cx Ca,
Address hyperkalemia
Obstruction due to OTC cold
medicine on top of BPH
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

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