Acute kidney Injury - Budapest Nephrology School

Acute kidney injury
Jan T. Kielstein
Deaprtment of Nephrology and Hypertension
Medical School Hannover

Acute kidney injury
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of AKI / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

Acute renal failure
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of ARF / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

Acute renal failure
Acute Kidney Injury

Acute kidney injury network: report of an initiative to
improve outcomes in acute kidney injury
MEHTA et al Crit Care Med, 11:2, R21, 2007
General Definition:
Acute kidney Injury (AKI) is defined as functional or
structural abnormalities or markers of kidney damage
including abnormalities in blood, urine or tissue tests or
imaging studies present for less than three months
Diagnostic criteria for AKI :
an abrupt (within 48 hours) reduction in kidney function :
• absolute increase in serum creatinine of either > 0.3 mg/dl
(>25 micromole/L) or a percentage increase of 50% or
• a reduction in urine output (documented oliguria of < 0.5
ml/kg/hr for > 6 hours)

AKIN Criteria
MEHTA et al Crit Care 11:R31, 2007
Stage Serum creatinine Urine output
1 Rise of serum creatinine > 0,3 mg/dl or
> 150–200% from baseline
2 Rise of serum creatinine 200–300% from
baseline
< 0.5 ml/kg/h for at least 6
hours
< 0.5 ml/kg/h for at least 12
hours
3 Rise of serum creatinine > 300% from baseline < 0.3 ml/kg/h for at least 24 h
or anuria > 12 h
Not everybody that pees has healthy kidneys!

ARF - definition, outcome measures, animal models, fluid
therapy and information technology needs
BELLOMO et al Crit Care Med 8(4):R204-12, 2004

Only 50 % of patients with AKI regain their renal
function completely
CERDA et al. Clin J Am Soc Nephrol 3:881-886, 2008
10 %
50 %
10 %
30 %

Acute kidney injury
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of AKI / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

Hospitalization Discharge Diagnoses for Kidney Disease -
United States, 1980--2005
CDC MMWR 57(12);309-312, 2008
1.8
36.5

Acute Renal Failure in critically ill patients (n=29,260)
A multinational, multicenter study
UCHINO et al. JAMA 294:813-818, 2005
Overall mortality:
60.3 %

Effect of acute renal failure requiring renal replacement
therapy on outcome in (17,126) critically ill patients
METNITZ et al Crit Care Med 30: 2051-2058, 2002

Acute Renal Failure in critically ill patients (n=29,260)
A multinational, multicenter study
UCHINO et al. JAMA 294:813-818, 2005

AKI has an effect on other organ systems
SCHEEL et al Kidney Int. 74(7):849-51, 2008

Acute renal failure
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of AKI / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

Lack of renoprotective effects of dopamine and furosemide
during cardiac surgery
LASSNIGG et al. J Am Soc Nephrol 11(1):97-104, 2000

Diuretics, mortality and non-recovery
of renal function in ARF
MEHTA et al. JAMA 288: 2547-2553, 2002
Lasix without volume
is like thinking
without a brain
JTK

Meta-analysis: low-dose dopamine increases urine output
but does not prevent renal dysfunction or death
FRIEDRICH et al. Ann Intern Med 142:510-24, 2005
“Renal dose Dopa”
Works and the earth
is a disc
JTK

Intensive insulin therapy in critically ill patients
van den BERGHE et al. NEJM 345: 1359-1367, 2001

A randomized prospective trial to assess the role of saline
hydration on the development of contrast nephrotoxicity
TRIVEDI et al. Nephron Clin Pract 93(1):C29-34, 2003
Patients received either:
•saline at 1 mL/kg per hour
for 12 hours pre and post
procedure or
•nothing
incidence of ARF
3.7% 34.6%

Acute kidney injury
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of AKI / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

SDMA is an early marker of change in GFR after
living-related kidney donation
KIELSTEIN et al. Nephrol Dial Transplant. 26:324-8, 2011

Serum neutrophil gelatinase-associated lipocalin - NGAL
The Troponin of the Nephrologist
DEVARAJAN et al Nephrology 15, 419–428, 2010

Circulating miR-210 Predicts Survival in Critically Ill
Patients with Acute Kidney Injury
LORENZEN / KIELSTEIN et al Clin J Am Soc Nephrol. 6:1540-6

Timing of renal replacement therapy initiation in acute
renal failure: a meta-analysis.
SEABRA et al. Am J Kidney Dis. 52(2):272-84, 2008
Urea : 21 – 67 mmol/l 27 - 71

Timing of renal replacement therapy initiation in acute
renal failure: a meta-analysis.
SEABRA et al. Am J Kidney Dis. 52(2):272-84, 2008
5 randomized prospective studies
1971 - 2006

Timing of renal replacement therapy initiation in acute
renal failure: a meta-analysis.
SEABRA et al. Am J Kidney Dis. 52(2):272-84, 2008

Serum neutrophil gelatinase-associated lipocalin at
inception of renal replacement therapy predicts survival in
critically ill patients with acute kidney injury
KUEMPERS et al. Critical Care 2010, 14: R9

Serum neutrophil gelatinase-associated lipocalin at
inception of RRT predicts survival in critically ill
patients with acute kidney injury
KÜMPERS et al Crit Care 14(1):R9, 2010

Timing of renal replacement therapy and clinical outcomes
in critically ill patients (n=1,238) with
severe acute kidney injury.
BAGSHAW et al. J Crit Care. 24(1):129-40, 2009

Acute kideny injury
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of ARF / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

September 11 th 1945
•67-year-old Maria Schafstaat
•initial dialysis treatment lasted 690 min (i.e. 11.5 hours)
•blood flow was 116 ml/min
•urea reduction rate 69% (i.e. pre- and posttreatment urea
serum concentrations were 396 and 121 mg/dl)
•calculated urea clearance was 87 ml/min and Kt/V 1.40.
•patient went on to become nonoliguric, followed by
gradual recovery of urea clearance.
•patient survived her acute illness, left the hospital

EDD: the way Kolff treated ARF

Quantitating Urea Removal in Patients with ARF:
Lost Art or Forgotten Science?
HIMMELFARB & IKLITZER Seminars in Dialysis 13: 147–149, 2000
It is also uncanny how much this first
successful dialysis treatment resembles
slow, low efficiency dialysis (SLED) or
extended daily dialysis (EDD), now being
advanced as a new approach for renal
replacement therapy in patients with
acute renal failure.
Everything old is new again.

Arteriovenous Haemofiltration: A New and Simple
Method for Treatmentof Over-hydrated Patients
Resistant to Diuretics
KRAMER et al Klin. Wschr. 55, 1121-1122 , 1977

Practice patterns in the management of acute renal failure
in the critically ill patient: an international survey
RICCI et al. Nephrol Dial Transpl, 21: 690–696, 2006

Gentle
Effective
Nurse friendly
In€xp€nsiv€
User friendly
Safe
The GENIUS system

Biofilm in bicarbonate-based replacement
fluid circuits in CVVH
KANAGASUNDARAM et al. Kidney Int. 76: 682, 2009

Efficacy and cardiovascular tolerability of EDD in
critically ill patients: a randomized controlled study
KIELSTEIN et al. AJKD 43: 342-349, 2004

Creatinine [mg/dl]
Efficacy and cardiovascular tolerability of EDD in
critically ill patients: a randomized controlled study
KIELSTEIN et al. AJKD 43: 342-349, 2004
5
4
3
2
1
0
CVVH GENIUS
0 h 12 h 24 h

Efficacy and cardiovascular tolerability of EDD in
critically ill patients: a randomized controlled study
KIELSTEIN et al. AJKD 43: 342-349, 2004
UF volume
EDD 2.97� 0.55 L/12h
CVVH 3.28 � 0.39 L/24 h
Norepinephrine dose at 0 h
EDD 0.47 � 0.11
CVVH 0.47 � 0.14 μg/kg/min
Norepinephrine dose at 12 h
EDD 0.45 � 0.12
CVVH 0.42 � 0.13 μg/kg/min

Continuous versus intermittent renal replacement therapy
for critically ill patients with AKI: a meta-analysis.
BAGSHAW et al. Crit Care Med. 36(2):610-7, 2008

Back to the future: extended dialysis for
treatment of acute kidney injury in the ICU
KIELSTEIN / SCHIFFER / HAFER J Nephrol 23:494-501, 2010

Dialysing the patient with acute renal failure in the ICU:
the emperors clothes?
LAMEIRE et al Nephrol Dial Transplant 14:2570–2571, 1999
„We firmly believe that to ensure optimal
dialysis treatment for the ARF patient in the
ICU, the skills and the experience of the
physicians and nurses who perform dialysis
are more important than the applied dialysis
modality.“

Acute kideny injury
1) Definition of acute renal failure / kidney injury
2) AKI – a deadly syndrome
3) Prevetion of AKI / What does (NOT) work ?
4) Timing of renal replacement therapy
5) Modes of renal replacement therapy
6) Dose of renal replacement therapy

Practice patterns in the management of acute renal failure
in the critically ill patient: an international survey
RICCI et al. Nephrol Dial Transpl, 21: 690–696, 2006
They don’t know what
they are doing

Intensities of Renal Replacement Therapy in Acute Kidney
Injury: A Systematic Review and Meta-Analysis
JUN et al. C-JASN 5: 956–963, 2010

Hypophosphatemia as a surrogate marker for inadequate
drug dosing ?
The VA/NIH Acute Renal Trial network NEJM 359:7-20, 2008
The RENAL Replacement Therapy Study Investigators NEJM 361:1627-38 ,2009

Dosing regimen from the vinyl age
for RRT of the i-Pod era?
CAVH
Cuprophane

Effect in higher RTT on mortality and its relation to the
number of septic patients in the study
Kielstein, unpublished
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Recommendations
Renal replacement therapy for AKI:
• WHEN ? ?.....maybe “early”
• WHAT?
– Method ?.....HD / CVVH / EDD
– Membrane synthetic/(doesn't matter)
• HOW ? medium dose range ?
• WHO? Nephrologist !!!

Its better to pee slowly than
to dialyse fast!