Acute Kidney Injury 2013

acute renal failure
…from basics to the latest advances
Joel M. Topf, MD
Clinical Nephrologist
http://pbfluids.com

Dr. Haas invented the first dialysis machine designed
for humans and in 1928 he treated 6 patients.

Dr. Haas invented the first dialysis machine designed
for humans and in 1928 he treated 6 patients.
All of them died. 

In 1943, Willem Kolff’s, working in Nazi
occupied Netherlands created the
second human dialysis machine from
a washing machine, juice cans and
sausage casings.
In 1943 he dialyzed his first patient, a
young man with acute nephritis.

sausage casings.


sausage casings.
 

sausage casings.
 
 Dr. Haas

sausage casings.
 
0 for 22

sausage casings.
In 1945, a 67-year-old woman in
uremic coma presented to Dr Kolff.
 
0 for 22

sausage casings.
In 1945, a 67-year-old woman in
uremic coma presented to Dr Kolff.
 
Regained consciousness after 11
hours of hemodialysis.
0 for 22

0
20
40
60
80
Mortality(%)
75
45
Sepsis Other Causes
Mortality by Etiology
 Commonly quoted
mortality of 70% is
for dialysis requiring
ICU patients
 For hospital acquired
ARF: 20%

 Patients with primary diagnosis of AKI have
higher mortality when they are:
 admitted on week-ends
 admitted to smaller hospitals
James et al. Weekend Hospital Admission, Acute Kidney Injury, and Mortality.
Journal of the American Society of Nephrology (2010) vol. 21 (5) pp. 845-851

ICU associated AKI is
characterized by a
d e l a y b e t w e e n
a d m i s s i o n a n d
d e v e l o p m e n t o f
acute renal injury

Risk
Injury
Failure
Loss of function
End-Stage Renal disease
rifle criteria for
stratifying arf

Risk
 Increase in Cr of 1.5-2.0 X baseline or
 urine output < 0.5 mL/kg/hr for more than 6 hours.
Injury
Failure
Loss of function

Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury
 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.
Failure
Loss of function

Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure
 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.
Loss of function

Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr >
24 hrs or anuria for more than 12 hours
Loss of function
 persistent renal failure (i.e. need for dialysis) for more than 4
weeks.

Loss of function: Need for dialysis for more than 4 weeks
 persistent renal failure (i.e. need for dialysis) for more than 3
months.

Loss of function: Need for dialysis for more than 4 weeks
End-Stage Renal disease : Need for dialysis for more than 3
months

nice criteria. do they work?
 20,126 consecutive
admissions to a
university hospital
 Excluded kids
 Kidney transplant and
dialysis patients
 Patients admitted for <
24 hours
 Using RIFLE:
 Risk 9.1%
 Injury 5.2%
 Failure 3.7%
Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.

nice criteria. do they work?
 20,126 consecutive
admissions to a
university hospital
 Excluded kids
 Kidney transplant and
dialysis patients
 Patients admitted for <
24 hours
 Using RIFLE:
 Risk 9.1%
 Injury 5.2%
 Failure 3.7%
No Renal failure
82%
Failure
4%
Injury
5%
Risk
9%
Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.

>3xBLCr
Cr>4
HospitalMortality

nice criteria. do they work in the icu?
 University of Pittsburgh
has 7 ICUs
 5,383 patients
 Excluded dialysis
 Subsequent admissions
 Frequency of acute
Kidney failure:
 No AKD 1,766
 Risk 670
 Injury 1,436
 Failure 1,511
Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

nice criteria. do they work in the icu?
 University of Pittsburgh
has 7 ICUs
 5,383 patients
 Excluded dialysis
 Subsequent admissions
 Frequency of acute
Kidney failure:
 No AKD 1,766
 Risk 670
 Injury 1,436
 Failure 1,511
No Renal failure
33%
Failure
28%
Injury
27%
Risk
12%
Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

No AKI Risk Injury Failure
0
5
10
15
20
25
30
RRT
LOS
ICU LOS
Mortality

AKIN criteria
 refinement of RIFLE criteria
 smaller change in Cr 0.3
 time constraint of 48 hours for the diagnosis of
AKI
 anyone requiring dialysis is stage 3 AKI

RIFLE v AKIN
RIFLERIFLE
R
Cr increased by
50-100%
I
Cr increased by
100-200%
F
Cr increased by more
than 200% or Cr > 4
L
Need for dialysis for >
4 weeks
E
Need for dialysis for >
3 months

RIFLE v AKIN
RIFLERIFLE
R
Cr increased by
50-100%
I
Cr increased by
100-200%
F
than 200% or Cr > 4
L
E

RIFLE v AKIN
RIFLERIFLE AKINAKIN
R
Cr increased by
50-100%
1
Cr increased by 0.3 or
50-100%
I
Cr increased by
100-200%
2
Cr increased by
100-200%
F
than 200% or Cr > 4
3
than 200%, Cr > 4, or
renal replacement
therapyL
than 200%, Cr > 4, or
renal replacement
therapy
E

AKIN vs RIFLE
120,123 critically ill patients in
57 ICUs in New Zealand and
Australia

AKIN vs RIFLE
Australia
64%
16%
14%
6%
RIFLE
63%
18%
10%
9%
AKIN
None
Risk / 1
Injury / 2
Failure / 3

AKIN vs RIFLE
Australia
64%
16%
14%
6%
RIFLE
63%
18%
10%
9%
AKIN
None
Risk / 1
Injury / 2
Failure / 3
2.24
3.95
5.13
2.45
4.23
5.22
Risk / 1
Injury / 2
Failure / 3
mortality odds ratio vs no AKI

oliguria: sensitive or specific?
 oliguria is a biomarker of ARF
 Used in the definition of RIFLE and AKIN
 How good is it at predicting AKICreatinine

 ICU patients and tracked hourly urine
outputs
 oliguria: <0.5 ml/kg/hr
 primary outcome: how predictive was oliguria
for subsequent AKI as defined by creatinine
 239 patients, 723 days, 23 cases of hospital
acquired AKI

duration of oliguria AKI the next day No AKI next day
None 5 443
≥1 hour 18 257
≥2 hours 15 194
≥3 hours 13 125
≥4 hours 12 95
≥5 hours 7 75
≥6 hours 5 50
≥12 hours 4 9

T h i s d e l a y i n t h e
development of AKI is
an opportunity.

T h i s d e l a y i n t h e
development of AKI is
an opportunity.
Often AKI is the result
of a second hit. Don’t
hit your patient.

risk factors for AKI
 CKD
 Age >75
 Peripheral vascular
disease
 Heart failure
 Liver disease
 Diabetes
 Nephrotoxins
 NSAIDs
 Aminoglycoseide
 Hypotension
 Hypovolemia
 Cardiac disease
 Iatrogenic
 Sepsis

etiologies of arf
 Seventy percent have concurrent oliguria
 < 400 mL/day
 < 0.5 mL/kg/hr in children
 < 1 mL/kg/hr in infants
 Complicates 5-7% of hospitalizations

Community acquired
49.7%
Hospital acquired
50.3%
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.

hospital acquired acute renal failure
Sepsis
7%
Other
2%
CHF
4%
Unknown
3%
Other
7%
Obstruction
2%
Hypotension
11%
Volume Contraction
21%
Post-Op
15%
Contrast
11%
Medication
16%

hospital acquired acute renal failure

differentiation of prerenal from
intrinsic renal disease

Excreted Na
Filtered Na
Fractional excretion of
sodium:

Excreted Na = Urine Na x Urine Volume
Calculating the Numerator

Calculating the Denominator
Filtered Na = Serum Na x GFR

GFR = Urine Cr x Urine Volume

Serum Cr

GFR = Urine Cr x Urine Volume

Serum Cr
Filtered Na = Serum Na x UrCr x UrVol

Serum Cr

Excreted Na
Filtered Na
FENa =

Excreted Na
Filtered Na
FENa =
FENa =

Excreted Na
Filtered Na
FENa =
Urine Na x Urine Volume
FENa =

Excreted Na
Filtered Na
FENa =
Serum Na x UrCr x Urine Volume

Serum Cr
FENa =

Excreted Na
Filtered Na
FENa =

Serum Cr
FENa =
Urine Na
Serum Na x UrCr
Serum Cr
FENa =

Excreted Na
Filtered Na
FENa =

Serum Cr
FENa =
Urine Na
Serum Na x UrCr
Serum Cr
FENa =
Urine Na x Serum Cr
Serum Na x UrCr
FENa =

FENa the easy way
 FENa is a small number 0.1% to 3%

FENa the easy way
 So the calculation will be 0.001-0.03 prior to
converting to percent by X 100

FENa the easy way
 So make the fraction small by putting the small
numbers over the big numbers

 Sr Na
FENa the easy way

 Sr Na
Sr Na
FENa the easy way

 Sr Na
 Sr Cr
Sr Na
FENa the easy way

 Sr Na
 Sr Cr
Sr Na
Sr Cr
FENa the easy way

 Sr Na
 Ur Na
 Sr Cr
Sr Na
Sr Cr
FENa the easy way

 Sr Na
 Ur Na
 Sr Cr
Sr Na
Sr Cr x Ur Na
FENa the easy way

 Sr Na
 Ur Na
 Ur Cr
 Sr Cr
Sr Na
Sr Cr x Ur Na
FENa the easy way

 Sr Na
 Ur Na
 Ur Cr
 Sr Cr
Sr Na
Sr Cr x Ur Na
x Ur Cr
FENa =
FENa the easy way

Why is the feNa high in ATN
 Normally tubules reabsorb 98-99% of the
filtered sodium

serum Na x GFR x minutes in a day
urinary Na excretion
filtered sodium

filtered sodium
140 x 0.1 x 1440
180

filtered sodium
20160
180

filtered sodium
0.8%

filtered sodium
0.8%
 So does ATN cause the tubules to fail to
reabsorb the 99%?

filtered sodium
0.8%
 So does ATN cause the tubules to fail to
reabsorb the 99%?
NO

false positive FeNa
 Contrast nephropathy
 Acute glomerulonephritis
 ATN with heart failure
 ATN with burns
 ATN with cirrhosis

 ATN with burns
Low FeNa not pre-renal

 ATN with burns
Low FeNa not pre-renal
these are cases of ATN where the
tubules effectively hold on to sodium

filtered sodium but now the GFR is 30 not 100
 The fena reflects the behavior of the tubules
that are undamaged. Tubules affected by
ischemia have a GFR of zero.

serum Na x GFR x minutes in a day
urinary Na excretion

140 x 0.03 x 1440
180

6048
180

2.9%

Acute renal success
 GFR is normally 100
mL/min
 Total plasma volume
is only 3 liters
 without massive
fluid reabsorption,
30 minutes to filter
all the plasma

Acute renal success
 GFR is normally 100
mL/min
 Total plasma volume
is only 3 liters
 without massive
fluid reabsorption,
30 minutes to filter
all the plasma
Tubuloglomerular feedback

Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54.
fractional excretion of urea
 Based on the physiologic increase in urea
reabsorption with pre-renal azotemia
 Normal FE Urea is 50-65% in well hydrated
individuals
 In prerenal azotemia this falls below 35%
 Not affected by diuretics
Sr Na
Sr Cr x Ur Na
x Ur Cr
FENa =

Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54.
fractional excretion of urea
 Based on the physiologic increase in urea
reabsorption with pre-renal azotemia
 Normal FE Urea is 50-65% in well hydrated
individuals
 In prerenal azotemia this falls below 35%
 Not affected by diuretics
Sr Urea
Sr Cr x Ur Urea
x Ur Cr
FEurea =

Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229
FEurea in the differential diagnosis
of atn
 102 patients with ARF
 Gold standard was consultants full analysis
and retrospective analysis of response to
treatment.
 Divided the cases into:
 ATN
 Prerenal without diuretic
 Prerenal treated with diuretics

0
25
50
75
100
Sensitivity(%)
92
50
91 90
Pre-Renal, No diuretics Pre-Renal, Diuretics
FENa
FEUrea

outcomes
Nephrology Dialysis Transplantation 23 2235-41, 2008
Clin J Am Soc Nephrol 3: 881-886, 2008

Acute kidney injury
as a cause of CKD
 3,679 diabetic veterans
 baseline creatinine 1.1, average age 61
 primary outcome: development of CKD 4
 secondary outcome: all-cause mortality
 1,822 hospitalized
 530 developed AKI at least once
 88% AKIN 1
 12% AKIN 2, 3

 39,805 Kaiser Permanente
 Hospitalized 1996-2003
 all had pre-hospitalization GFR <45
 among those who developed ARF (50%
increase in Cr and dialysis)
 26% died in the hospital
 among survivors:
 GFR 30-44 42% required permanent dialysis within a
month of discharge
 GFR 15-29 63% required permanent dialysis within a
month of discharge

26%
5%
20%
49%
ARF in hospital
Death in Hosp Died after d/c Alive, No dialysis ESRD
5%
4%
90%
2%
No ARF in hospital

34.7%
27.6%
28.4%
45.2%
14.4%
77.0%
Death during Hospital
ESRD after D/C
GFR 30-44 GFR 15-29 GFR <15

even the lucky ones, not so lucky
Survivors of ARF, not dialysis dependent
No ARF
dialysis-freesurvival

used to be...
No dialysis.
No foul.

Acute renal failure is a risk factor
for progression of CKD
Acute renal failure is a risk factor
for progression of CKD

therapy
Internist management
Patient empowerment
Renal replacement therapy

Internist management
 Monitor I’s and O’s,
daily weights
 Frequent labs
 BMP, phosphorous,
albumin, U/A
 Consult nephrology
 Avoid hypotension
 Dose adjust for
renal failure
 Follow-up after d/c
for high risk of CKD
 Avoid
 Iodinated contrast
 Aminoglycosides
 ACEi/ARB
 Thoughtful fluid
management

Patient empowerment
 talk to patients about what to do if they
become acutely ill
 increase fluid intake
 decrease diuretics
 monitor blood pressure

Dialysate
140
5.8
108
17
76
7.8
145
2
110
35
0
0
Conventional Dialysis: combination of diffusive and convective
Clearance
140
5.8
108
17
67
3.8
Blood
Ultra-filtrate

136
5.8
108
17
67
3.8
Isolated Ultrafiltration: CHF Solutions
Minimal clearance

136
5.8
108
17
67
3.8
136
5.8
108
17
67
3.8
Minimal clearance

136
5.8
108
17
67
3.8
136
5.8
108
17
67
3.8
80 mmol KIsolated Ultrafiltration: CHF Solutions
Minimal clearance

136
5.8
108
17
67
3.8
136
5.8
108
17
67
3.8
80 mmol K
5.8 mmol/L
Minimal clearance

136
5.8
108
17
67
3.8
136
5.8
108
17
67
3.8
80 mmol K
5.8 mmol/L
= 13.8 litersIsolated Ultrafiltration: CHF Solutions
Minimal clearance

Ultrafilter 3+
liters/hour
Replace all ultrafiltrate
with sterile fluid at ideal
plasma concentrations
136
5.8
108
17
67
3.8
140
2
108
30
0
0
CVVH
Convective clearance

Ultrafilter 3+
liters/hour
Replace all ultrafiltrate
with sterile fluid at ideal
plasma concentrations
136
5.8
108
17
67
3.8
140
4
108
30
0
0
CVVH

Post-filter replacement fluid
CVVH

Pre-filter replacement fluid
CVVH

CVVHDF
Convective and Diffusive

high dose dialysis
survival
Severity of illness (CCARF Score)

high dose dialysis
survival
Low dose

high dose dialysis
survival
High dose
Low dose

Ronco’s landmark dialysis dose
study
 425 patients with dialysis dependent acute
renal failure were randomized to one of three
doses of CVVH
 20 mL/kg/hr of effluent
 35 mL/kg/hr
 45 mL/kg/hr

20 mL/kg/hr
35 mL/kg/hr
45 mL/kg/hr
Ronco C, Bellomo R, Hormea P, Et al. Lancet 2000; 355: 26-30.

Ronco
425 CVVH 20/h vs. 35-45 ml/kg/h*
Bouman
106 CVVH 20ml/kg/h* vs. 48 ml/kg/h
Schiffl
160 Alternate day vs. daily hemodialysis
Saudan
206 CVVH 25 ml/kg/h vs. CVVHDF 42 ml/kg/h
Total (fixed effects)
Total (random effects)
1 10
Odds ratio
Study
n
treatment groups
*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).
Kellum J. Nature Clin Practice Nephrol 2007 3: 128-9.

ATN trial
 US trial
 Prospective randomized, multi-center trial
 27 institutions
 primarily veterans hospitals
 Dose finding study, modality agnostic
 Conventional
dialysis
 SLED
 CVVH
 CVVHD
 CVVHDF

endpoint
 Primary Endpoint:
All-cause mortality at day 60.
 Secondary endpoints:
 In-hospital death
 Recovery of renal function (CrCl>20)
defined as complete if Cr was <0.5 over the baseline
 Duration of renal replacement therapy
 Dialysis free at 60 days
 Duration of ICU stay
 Return to previous home at day 60

results
563 enrolled in standard care
561 randomized to intensive therapy

 60% sepsis
 80% vented
 Apache II score 26
predicted mortality 55%
 BUN at initiation
of RRT 65
 half in the MICU
half in the SICU

This report currently should be viewed as
the deﬁnitive 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.

 Patients stratified by net fluid gain from
admission to initiation of CRT
Fluid in – fluid out
ICU admit weight X 100

 longer ICU stay
 higher mortality
 more multi-organ
dysfunction
 more likely to be
intubated
 more inotropes
 more sepsis
 higher PRISM score
More fluid. More sick.

Worse ﬂuid overload severity remained
independently associated with mortality (OR,
1.03; 95% CI, 1.01-1.05). The relationship
was satisfactorily linear and the OR suggests a
3% increase in mortality
for each 1% increase
in degree of ﬂuid overload
at CRRT initiation.

 80 kg adult
 Is and Os: 2,400 mL in (100 mL/hr) and
1,600 mL of urine (67 mL/hr)
 Positive balance of 800 mL. If after 3 days the
patient becomes oliguric with 200 mL of
urine output for two days (2,200 mL positive
per day) before initiating CRT.
 That patient would be up 6,800 mL or 8% of
bodyweight
 24% increase in mortality compared to
someone with matched ins and outs

 observational data from SOAP study of ICU
care in Europe
 198 ICUs
 24 countries
 147 patients
 1120 had AKI
 ARF defined as a Cr >3.5 or urine output <
500 mL

Moreover, this would suggest that
prevention or management of
ﬂuid overload is evolving as a
primary trigger/indicator for
extra-corporeal ﬂuid
removal, and this may be
independent of dose delivery or solute
clearance.
Critical Care 2008, 12:169

summary
 Prognosis is grim
 We have two validated, consensus definitions
 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
 AKIN
 Stage 1
 Stage 2
 Stage 3

summary
 FE of Urea is a validated way to separate pre-renal
from AKI even in the presence of diuretics
 Use of high dose dialysis regardless of methodology
offers no survival benefit
 Do not fluid overload your patient
 Dopamine doesn’t work

Acute kidney injury is not a
specialist’s emergency; it is seen
commonly in acute medicine
and, as such, it is essential
that all physicians have the
conﬁdence and skills to
identify and manage it.

Acute Kidney Injury 2013

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