Transcript Acute Renal Failure

Acute Renal Failure
in the ICU
Review of Anatomy and
Physiology
Glomerulus
-forms ultrafiltrate of
plasma
Review of Anatomy and
Physiology
Proximal Tubule
-reabsorbs isosmotically
65-70% of
-reclaims all the glucose,
amino acids, and
bicarbonate
Secretes protein bound
drugs
Review of Anatomy and
Physiology
Loop
-reabsorbs 15-25% of
filtered NaCl
-Creates the gradient for
the countercurrent
multiplier
Review of Anatomy and
Physiology
Distal Tubule
-reabsorbs few percent
-fine tunes- volume,
osmolarity (ADH), K
(aldosterone), acidbase
Background
• ARF- an abrupt reduction in renal function
sufficient to result in azotemia.
Case Presentation
• 88 yo wf with MMP including: CHF, NIDDM,
HTN, COPD, and CAD, presents with 3 day h/o
subjective fevers, chills, headache, night sweats,
flank pain, dysuria, and mild confusion.
• Vitals t 103 p120 rr13 pox 98% RA
• Exam – Right flank tenderness
• 140/100/50
--------------3.0/30/1.1
Presentation (cont)
• ER course
– CXR negative
– As patient appeared “ill”, arrangements made
for ICU admission for treatment of presumed
urosepsis
– Prior to admission- given Toradol 40mg IM for
her headache. Narcotics avoiding 2nd to
concern of clouding the picture regarding her
mental status changes
Glomerular Filtration Rate
• Direct measure of renal function
– reduced prior to the onset of symptoms of renal failure
– impairment of GFR correlates with structural
abnormalities seen on biopsy
• Normal GFR is approximately 120cc/min
– Decreases with age- by age 80, GFR 80
– Asymptomatic metabolic abnormalities
(hyperphosphatemia, hypocalcemia, anemia,
hyperparathyroidism, osteoporosis) begin at a GFR of
< 50 cc/min
– Dialysis usually initiated at GFR < 10 cc/min
Glomerular Filtration Rate
• Difficult to directly measure
– as a result in clinical practice we usually
estimate from serum creatinine or creatinine
clearance.
GFR vs. Serum Creatinine
- For early disease, serum
creatinine is a poor marker of
GFR
35
-lose of 50% of function without
a change in Cr
30
Serum Creatinine
- example- transplant donor
25
-For late disease, serum creatinine
is a poor marker of GFR
20
-large change in creatinine is a
minimal change in GFR
15
- example- Cr change from 3
to 4 is a change in GFR of
only a few cc/min (3cc/min in
this pt)
10
-Serum creatinine only valid in
steady-state
5
0
120
100
80
60
40
Glomerular Filtration Rate
20
15
2
-ie immediately after a
bilateral nephrectomy–
serum creatinine initially
normal
Creatinine Clearance
• Effort to improve on the poor results
obtained by using serum creatinine
• Creatinine is generated from muscle
metabolism of creatine
– Therefore proportional to muscle mass
• Age
• Sex
• Weight
Creatinine Clearance
• Most commonly used equation is the Cockcroft
Gault Equation
– Attempt to account for variable muscle mass
• ((140-age) * weight (kg) ) / (72 *serum creatinine)
• *.85 for females
– Derived from approximately 100 white Canadian males
without renal disease
• Yet we extrapolate to everyone
• As a result– average error 15%
– can be >50% off in 10% of cases
– Not uncommon to have a normal serum creatinine with a GFR as
low as 20 cc/min
Our little old lady
• Her baseline serum creatinine = 1.1
– “Normal” per the computer values– therefore
ER didn’t think twice about administering
NSAID
– Cockcroft-Gault
• Calculated CrCl of 27cc/min– or consistent with
moderate to severe renal failure
– 24hr post Toradol, Scr increased to 1.5
• CrCl decreased by 25% to 20 cc/min
NSAID associated ARF
• Primarily hemodynamically mediated
• Renal physiology
Afferent
Efferent
Glomerulus
NSAID associated ARF
A diseased kidney or a patient with effective
volume depletion (CHF, cirrhosis, dehydration,
etc) relies upon prostaglandins to dilate the
afferent arteriole to maintain adequate
perfusion/GFR
Prostaglandins
Afferent
Efferent
Glomerulus
NSAID associated ARF
NSAIDS block prostaglandins
-In musculoskeletal injury this limits vasodiliation and
resultant swelling around sites of injury
-but unfortunately also blocks PGs in the kidney
Prostaglandins
Afferent
Prostaglandins
NSAIDS
Efferent
Afferent
Efferent
Glomerulus
Glomerulus
NSAID associated ARF
Normal baseline renal function
Prostaglandins
Afferent
Afferent
NSAIDS
Efferent
Efferent
Glomerulus
Glomerulus
Because there is no baseline PG production, NSAIDS
have no effect on renal function in patients with
normal volume and renal function
NSAID associated ARF
Baseline abnormal renal function or baseline
PG dependent
Cirrhosis, CHF, renal
disease or volume depleted
Prostaglandins
Prostaglandins
Afferent
NSAIDS
Afferent
Efferent
Efferent
Glomerulus
Glomerulus
Because there is baseline PG production which is
blocked by NSAIDS, the effect is a resultant increased
creatinine
NSAID associated ARF
Baseline abnormal renal function or baseline
PG dependent
• In this case the creatinine bump is analogous to
angina
– It is a manifestation of decreased renal blood flow
• If addressed in the early stages, it is associated with no
permanent damage
– Discontinuation of NSAIDS will usually lead to a complete
reversal of an increased serum creatinine
• If allowed to persist, can result in irreversible renal damage
– Unfortunately, the only way to know the damage is irreversible it
to wait until it occurs
• Impact of ASA qd?
Little old Lady
• ARF noted and no further NSAIDS given
• On admission, she was noted to be have
hypertension. Given her history of CHF,
addition of an ACE-I was felt indicated.
Lisinopril 20mg po qd added to her
regimen.
• The following day, her serum creatinine
was back to 1.5. Why?
ACE-I and renal function
• Like NSAIDS, the bump in serum
creatinine is primarily hemodynamically
mediated
Afferent
=Ace-I effectanalogous to
removing the end
cap from the hose
Efferent
Glomerulus
ACE-I and renal function
• Unlike NSAIDS which bump the creatinine
by starving the kidney for blood, ACE-Is
bump the creatinine, but in the process
actually increases renal blood flow.
Afferent
=Ace-I effectanalogous to
removing the end
cap from the hose
Efferent
Glomerulus
Little old Lady
• As patient trending toward hypotension, ACE-I
d/cd. Creatinine decreased back to 1.3.
• Urine culture positive for GNR sensitive to cipro
or bactrim. To minimize the development of
flouroquinolone resistance, ICU avoids levaquin
and prescribes Bactrim for presumed urosepsis
• The next day the patient’s serum creatinine has
again increased to 1.5
• What happened?
Bactrim and Serum creatinine
• Creatinine is removed from the body by
glomerular filtration and by active transport
in the proximal tubule
– In patients with normal renal function,
approximately 10% of the daily load is secreted
– As renal failure progresses, the proportion can
increase to up to 50%
Bactrim and Serum creatinine
• Bactrim competes with creatinine for the limited number
of active transporters
– Once saturated- every molecule of bactrim transported is one less
molecule of creatinine secreted– resulting in increased serum
creatinine WITHOUT A CHANGE IN RENAL FUNCTION
• Minimal bump if low serum creatinine (recall you can lose 50% of
function without a change in serum creatinine). But a large bump is
serum creatinine already elevated (because depend on transporter to
remove up to 50% of creatinine and on steep part of curve)
creatinine
creatinine
bactrim
bactrim
creatinine
creatinine
bactrim
creatinine
bactrim
creatinine
bactrim
creatinine
creatinine
creatinine
bactrim
creatinine
bactrim
Tubule
Blood
bactrim
bactrim
bactrim
Urine Space
Little old Lady
• Remains febrile so switched to levaquin and
gentamicin. Forty-hours later, Scr now
elevated to 2.2 and associated with oliguria.
• Was it gentamicin nephrotoxicity?
Aminoglycoside Nephrotoxicity
• Aminoglycosides are non-protein bound
and freely filtered at the level of the
glomerulus. Renal excretion is the major
route of elimination.
• Accumulate in the tubules where they cause
toxicity
– Injury visible by EM and light microscopy
Gentamicin Nephrotoxicity
• No hard and fast rule regarding toxicity
– Dependent upon duration and total dose
– Risk factors- old age, volume depleted,
hypomagnesemia
– Extremely rare before 72hours. Earliest onset typically
at 5-7 days.
– Presents with rising BUN/creatinine associated with
POLYURIA and other signs of tubular dysfunction
• Proteinuria, bicarb wasting, hypomagnesemia
Gentamicin Nephrotoxicity
• Why polyuria?
GFR of 120cc/min
equals 173 liters of
ultrafiltrate per day
Afferent
If nl urine output 1 liter
per day, tubules
reabsorb 172/173 liters
or 99.4% of the UF
Efferent
Glomerulus
Proximal Tubule
-reabsorbs 70-80% of total
volume
-reabsorbs all glucose,
protein, and bicarb
If tubule damaged (by
gentamicin or other
nephrotoxin), even a
2% decrease in
reabsorption results in
an extra two liters of
urine per day
Gentamicin Nephrotoxicity
• No specific therapy beyond stopping the
medication
• Consider non-nephrotoxic replacement. If must
have an aminoglycoside– tobramycin is less
nephrotoxic
• Will take days to weeks to resolve as the
gentamicin is gradually released from the tubules
– Used to therapeutic advantage in treating UTIs
Gentamicin Nephrotoxicity
• Peaks and Troughs
– “Peaks kill bugs, troughs kill kidneys”
– Not that simple
•
•
•
•
Mix of peaks, troughs, and overall duration
Peak studies derived using troughs of 6-7
Trough studies derived using very high peaks
My practice– if life threatening infection– aim for high troughs
(doesn’t do any good to preserve the kidneys and have the
patient die). Nephrotoxicity, if it occurs won’t be for many
days, by then you have either controlled the infection or lost
the patient.
– Experimental nephrotoxicity- canine studies
Gentamicin Nephrotoxicity
• QD dosing
50
45
40
35
30
25
20
15
10
5
0
Traditional
QD
42
30
18
6
Traditional
therapeutic range
Post-antibiotic effect
(concentration
independent killing)
Gentamicin Nephrotoxicity
40
Renal Insuff
QD
35
30
25
20
Traditional
therapeutic range
15
Post-antibiotic effect
(concentration
independent killing)
10
5
42
30
18
6
0
No antibiotic
coverage
Little old lady
• Continues to spike temperatures despite
multiple days of broad spectrum antibiotics.
What gets ordered next?
Little old lady
• Contrast CT scan to r/o peri-nephritic
abscess or other intra-abdominal process
• Serum creatinine 48 hours later 3.0
Contrast Nephropathy
-Reported incidence of acute renal failure is highly variable
(up to 50% depending upon the study)
-but renal failure in studies is typically defined as a
bump in Scr of 50% or 0.5 mg/dl
-clinically don’t care unless unless requires dialysisincidence of dialysis is much less
-Risk factors- diabetes, baseline renal dysfunction, chronic
renal insufficiency, relative volume depletion (CHF,
cirrhosis, ascites, nephrosis, diarrhea)
-Risk is OVERRATED
-Practically- unless serum creatinine >5.0-6.0 or diabetic with
serum creatinine >4.0, highly unlikely to experience
irreversible renal dysfunction or dialysis
Contrast Nephropathy
- Traditional teaching is that multiple myeloma is at
higher risk for contrast nephropathy– this is not
true
- Prevention of contrast nephropathy
- HYDRATION, HYDRATION, HYDRATION- NS vs.
½ NS- doesn’t matter
- Non-ionic better than ionic
- Minimize volume of contrast and use non-ionic contrast
- Mucomyst protocol--- Jury still out. Probably doesn’t
help.
Little old Lady
• No abscess noted
• Continues to spike temperatures s/p a week
on broad spectrum antibiotics
– What gets added next?
Little old Lady
• Amphotericin
– Polyene antibiotic that is the treatment of choice for the
majority of serious fungal infections.
– Works by attacking ergosterol in fungal membranes
• Acts like a MAC of human complement- literally “punches”
holes in the cell walls leading to osmotic cell death
• Cholesterol in mammalian cell walls is very similar
– Minor cross reactivity, increases with increased levels
– Where tissue is typically exposed to the highest drug levels in the
human body??
Amphotericin toxicity
• What tissue is typically exposed to the
highest drug concentrations?
– Kidney- especially the distal tubules where
urine concentration occurs.
– Therefore the cross-reactivity of amphotericin
for cholesterol is most severe in the distal
tubules of the kidney.
Amphotericin toxicity
• What are the
manifestations?
Distal Tubule
-reabsorbs few
percent
-fine tunesvolume,
osmolarity (ADH),
K (aldosterone),
acid-base
– All the distal tubule
functions- acid-base,
volume, potassium, Mg
• What can you do to
minimize?
Amphotericin toxicity
• Minimize toxicity
– NS loading
• Liposomal Amphotericin
Distal Tubule
-reabsorbs few
percent
-fine tunesvolume,
osmolarity (ADH),
K (aldosterone),
acid-base
– Decreased solubilizing
agent- which causes direct
nephrotoxicity
– Uptake primarily by the
RES cells- lower dose with
less net renal exposure
Little old Lady
Continues to spike through amphotericin and
progresses to frank hypotension with
pressures 60-80s for several hours
• Within 24hrs serum creatinine increased to
5.5, and continues to elevate 1 point per day
ATN
• Acute tubular necrosis
– Number one etiology of renal failure in the unit setting
– Usually 2nd to hypotension
– Manifest by isosthenuric urine, course and fine granular
casts in the urine sediment
– No effective therapy. Supportive treatment only
– Given no additional insults- usually reversible over a 46 week period
ARF in ICU
• Mortality severe
– MICU- 30-50%
– SICU- 50-75%
• Unchanged for 30 years- despite
tremendous advances in acute dialysis and
patient management.
• Why?
– Patients die with renal failure, not from it.
ARF in ICU
Management
• Conversion of non-oliguric to oliguric renal
failure
– Not a therapeutic maneuver– prognostic only
– Useful for assisting in volume management and
hyperkalemia, but no impact on ATN
– Nephrectomy analogy
ARF in ICU
Management
• Avoidance of dialysis – renal recovery will
be faster and more complete if dialysis is
not initiated
• Don’t exacerbate the situation
– No NSAIDS, contrast, avoid hypotension etc
ARF in ICU
Management
• Renal purpose is to maintain homeostasisvolume, acid-base, and electrolyte
• Volume
– Insensible losses 500-1000cc/day– if inputs less than
that– no volume issues
• KVO- even 10cc/hr (1 liter every four days—if HD only
removes one liter– that means an extra treatment each week
just for the KVO)
• Obviously maximally concentrate all IVs
• Sedation– use longer acting agent – volume of MSO4 is much
less than Fentanyl, BZ less volume than propofol
ARF in ICU
Management
• Renal purpose is to maintain homeostasisvolume, acid-base, and electrolyte
• Electrolytes (primarily K)
– Obviously don’t give exogenous K– hidden
sources include antibiotics, Lactated ringers,
unnecessary K in TPN
– Goal is < 60 meq/day for dialysis patient, none
for a ARF patient
ARF in ICU
Management
• Renal purpose is to maintain homeostasisvolume, acid-base, and electrolyte
• Acid-base
– Avoiding intake is not sufficient– body will generate
acid on a daily basis (2nd to protein catabolism)
• Bicarbonte will decrease approximately 2 qd– anything faster
means a superimposed acidosis
• Usually drops to a minimum of 10-12– then bone buffering
prevents further fall (pH 7.2ish)
• Could treat by giving bicarbonate– but a volume load
ARF in ICU
Management
• Renal purpose is to maintain homeostasisvolume, acid-base, and electrolyte
• Uremia
– Due to metabolism of proteins
• Urea itself it NOT a toxin– it is a surrogate marker for other
toxins which accumulate in renal failure
– Unfortunately, just like acids– cannot avoid problems
merely by avoiding input
• If you don’t have protein intake, body will simply metabolize
an equivalent amount of protein
– Therefore try to give an adequate amount (1gm/kg) to avoid
catabolism, but no extra
ARF in ICU
Management
• Drugs
– Renally-dosed
• Texts available, but general rule of thumb
• Loading dose is unchanged
• If protein bound, less likely to require renal dosing
ARF in ICU
Nursing implications
•
•
•
•
Avoid standing K or IVF orders
Dialysis access issues
Renally-dose medications
If on dialysis– try to arrange meds for after
dialysis
– Especially if medications normally cleared by the
kidney
• Blood draws can be performed with dialysis (if no
A-line present)