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Joel M. Topf, MD
Clinical Nephrologist
http://pbfluids.com
the house
moment
Dr. Haas invented the first dialysis machine designed
for humans and in 1928 he treated 6 patients.
Dr. Haas
80
Commonly quoted 70
mortality of 70% is 60
Mortality (%)
for dialysis requiring 50
ICU patients 40
30
For hospital acquired
20
ARF: 20%
10
0
Sepsis Other Causes
37 year old AA female
Multiple GSW
Prolonged hypotension
Aorta was cross
clamped during
exploratory laparotomy
Anuric x 18 hours
Cr from 0.8 to 2.2
36 y.o. African American
women with menorrhagia.
Has prolonged bleeding
following fibroidectomy
Contrasted CT scan used to
determine source of
bleeding.
Cr rises from 0.8 to 2.2
Patient is non-oliguric
Two women.
Same age.
Same race.
I njury
F ailure
L oss of function
E nd-Stage Renal disease
R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
I njury
increase in Cr 2-3 X baseline (loss of 50% of GFR) or
urine output < 0.5 mL/kg/hr for more than 12 hours.
F ailure
L oss of function
E nd-Stage Renal disease
R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
F ailure
increase in Cr rises > 3X baseline Cr (loss of 75% of GFR) or
an increase in serum creatinine greater than 4 mg/dL, or
urine output < 0.3 mL/kg/hr for more than 24 hours or
anuria for more than 12 hours.
L oss of function
E nd-Stage Renal disease
R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
F ailure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr >
24 hrs or anuria for more than 12 hours
L oss of function
persistent renal failure (i.e. need for dialysis) for more than 4
weeks.
20,126 consecutive
admissions to a Risk
university hospital 9% Injury
5%
Excluded kids
Kidney transplant and Failure
4%
dialysis patients
Patients admitted for <
24 hours
No
Using RIFLE: Renal
Risk 9.1% failure
82%
Injury 5.2%
Failure 3.7%
Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.
>3x BL Cr
Cr > 4
Hospital Mortality
nice criteria. do they work in the icu?
University of Pittsburgh
has 7 ICUs
Risk
5,383 patients 12%
No
Excluded dialysis Renal
Subsequent admissions failure
33%
Frequency of acute Injury
Kidney failure: 27%
No AKD 1,766
Risk 670 Failure
Injury 1,436 28%
Failure 1,511
25
20 Mortality
RRT
15
LOS
10 ICU LOS
0
No AKI Risk Injury Failure
RIFLE is dependent on creatinine.
creatine is a functional marker of
organ damage
Functional
markers: old
and busted
biomarkers are foot prints of actual
organ damage
Biomarkers,
new hotness
functional versus biomarkers
Functional
Marker Biomarker
SGOT
Hypoalbuminemia
Liver damage Coagulopathy
SGPT
GGT
functional versus biomarkers
Functional
Marker Biomarker
SGOT
Hypoalbuminemia
Liver damage Coagulopathy
SGPT
GGT
Troponin I
Hypotension
Heart damage Arrhythmia
Troponin T
CK-MB
functional versus biomarkers
Functional
Marker Biomarker
SGOT
Hypoalbuminemia
Liver damage Coagulopathy
SGPT
GGT
Troponin I
Hypotension
Heart damage Arrhythmia
Troponin T
CK-MB
Creatinine
KIM-1
Kidney damage BUN
NGAL
Cystatin C
creatinine as a lagging indicator
Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.
Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.
Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.
Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.
Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.
Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.
N=389 N=256 N=103
100% other
17 12 11
80% 11 Post Renal
7 20
Pre Renal
21 29
60% Renal
30
40%
56 48
20% 39
0%
< 65 65-79 > 79
Ages
Sepsis
Volume 7%
Contraction
22%
Medication
16%
Post-Op
15%
Contrast
11%
hospital acquired acute renal failure
Pre-renal azotemia
No BP, no pee pee
differentiation of prerenal from
intrinsic renal disease
Use of FENa
Fraction of filtered sodium which is excreted in the
urine.
Patients with prerenal azotemia will be sodium
avid and minimize renal excretion of sodium
Fractional excretion of
sodium:
Excreted Na
Filtered Na
Calculating the Numerator
Urine Na x Serum Cr
FENa = Serum Na x UrCr
FENa the easy way
Sr Na
Sr Cr Sr Cr x Ur Na
FENa =
Ur Na Sr Na x Ur Cr
Ur Cr
FeNa. what is it good for?
Miller, Schrier, Et al. Annals Int Med, 1978 Vol 89. p 47-50
Low
FENaFENa,
False Not pre-renal
Positive
Pre-renal Azotemia ATN tested too early
Contrast Nephropathy ATN with CHF
Hemoglobinuric ATN with cirrhosis
nephropathy ATN with severe burns
Myoglobinuric nephropathy Non-oliguric acute renal
Acute rejection failure
Cyclosporin and Tacrolimus Acute Glomerulonephritis
toxicity* ACEi in bilateral RAS or in
Hepatorenal syndrome RAS with solitary kidney
Acute interstitial nephritis NSAID induced ARF
FeNaFENa,
High false negatives
but pre-renal
Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229
FEUrea
FENa
100 92 91 90
80
Sensitivity (%)
60 50
FENa
40
FEUrea
20
0
Pre-Renal, No Pre-Renal, Diuretics
diuretics
therapy
Renal replacement therapy
Furosemide
Dopamine
Fenoldapam
hANP (Anaritide)
renal replacement therapy
Conventional Dialysis
Diffusive Clearance 67
136 108
5.8 17
3.8
0
145 110
2 35
0
Dialysate
Isolated Ultrafiltration: CHF Solutions 80 mmol K
= 13.8 liters
5.8 mmol/L
Minimal clearance 67
136 108
5.8 17
3.8
67
136 108
5.8 17
3.8
CVVH
Convective clearance 67
136 108
5.8 17
3.8
Ultrafilter 3+
liters/hour
High dose
survival
Low dose
35 mL/kg/hr
20 mL/kg/hr
70
60 10 9
Days
50 46 8
40 6
28
30
4
20
10 2
0 0
3 days/week HD Daily HD 3 days/week HD Daily HD
P=0.002
4.0 P=0.005
3.92
P=0.007
3.5 3.27
3.02
3.0
Odds Ratio
2.5
2.0
P=0.02
1.5
1.06
1.0
0.5
0.0
Apache III Oliguria Sepsis Alternate-
score day HD
59 59
60 60
P=0.03 P=0.008
50 50
39
Fraction (%)
Fraction (%)
40 40 34
30 30
20 20
10 10
0 0
CVVH CVVHDF CVVH CVVHDF
1 10
Odds ratio
*For purposes of analysis the two high-dose arms in Ronco were combined, as were the two low-dose arms in
Bouman. If these groups are removed the odds ratio is unchanged (1.94; P <0.001).
US trial
Prospective randomized, multi-center trial
27 institutions
primarily veterans hospitals
Dose finding study, modality agnostic
Conventional dialysis
SLED
CVVH
CVVHD
CVVHDF
interventions
Stable (intermittent
3 days a week 6 days a week
hemodialysis)
80% vented
Apache II score 26
(predicted mortality
55%)
BUN at initiation of
RRT 65
the definitive
viewed as
study defining
dialysis dosing in
critically ill patients with
AKI
H. David Hume
…the patient dies
from multi-organ
failure while in
exquisite electrolyte &
fluid balance .
Fluid balance?
Patients stratified by net fluid gain from
admission to initiation of CRT
higher mortality
more multi-organ
dysfunction
more likely to be
intubated
more inotropes
more sepsis
the OR 3%
suggests a
Retrospective review of
ICU patients
Diuretic responsiveness
determined survival
Increased urine
dopamine: still doesn’t work
Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.
P=0.235 P=0.163 P=0.068
40 38.7
35
Frequency (%) 30 27.5
25.3 25.3
25
20 Fenoldapam
16.25
15 13.8 Placebo
10
5
0
Dialysis or Death Dialysis Death
Frequency (%)
30
25.9 25
25
20 17.6
20
13 15
15
10 8.8
10
5 5
0 0
Dialysis or Death Dialysis Dialysis or Death Dialysis
Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.
Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.
prophylactic fenoldapam in sepsis
35 34
30
Frequency (%)
25
20 19.3 P=0.056
15 14 Fenoldapam
10 6.6
Placebo
5
0
Cr > 1.7 Cr > 3.5
Fenoldapam Placebo
atrial natriuretic peptide
30 minutes of ANP
before contrast
30 minutes of ANP after
contrast
Cr > 1.8
Randomized to placebo
or 1 of 3 doses of
anaritide
Creatinine increase of
0.5 or 25% defined RCN
Kurnik B, Allgren RL, Genter FC. Am J Kid Dis 1998; 31: 674-80.
50 47
45 43
504 critically ill patients
50
45
40
Hypotension (%)
35
30
p=0.008 25
20
15
10
5
0
Placebo Anaritide
97
100 100 100
90 90 P=0.51 90 P<0.001
80 80 80
Frequency (%)
Frequency (%)
Frequency (%)
70 70 70
56 60 58
60 60 60
50
P=0.22 50 50
40 40 40
30 21 30 30
20 15 20 20
10 10 10
0 0 0
Placebo Anaritide Placebo Anaritide Placebo Anaritide
Early treatment
50% increase in creatinine
Low dose anaritide
50 ng/kg/min vs 200 ng/kg/min
Anaritide run continuously until renal recovery or
dialysis.
Previous studies used 24 hour infusion
Protocol defined indication for dialysis
UO < 0.5 cc/kg/hr Pulmonary edema and
for 3 hours FiO2 >0.8
Cr > 4.5 K>6.0
Swärd K, Valsson F, Odencrants P, Et al. Crit Care Med 2004; 32: 1310-5.
N=61
Average Cr 2.3
100
90
80
Hypotension (%)
70
59
60 52
50
40
30
20
10
0
Placebo Anaritide
Swärd K, Valsson F, Odencrants P, Et al. Crit Care Med 2004; 32: 1310-5.
summary
Prognosis is grim
We now have a validated, consensus definition
R isk
I njury
F ailure
L oss of function
E srd
Outpatient and inpatient acquired ARF differ in
etiology
Hospital acquired disease is your fault
summary