Pediatric Acute Kidney Injury Management Insights
Pediatric Acute Kidney Injury:
Supportive Therapies
Jordan M. Symons
University of Washington School of Medicine
Seattle Children’s Hospital
Stage-Based Management of AKI
Kidney Intl Supplements (2012) 2: 19-36
Natural History of Acute
Kidney Injury (AKI)
What Goes Wrong in AKI?
V
o
l
u
m
e
i
s
s
u
e
s
•
Volume overload
–
Pulmonary edema
–
Tissue edema
–
Congestive heart
failure
•
Hypertension (+/-)
M
e
t
a
b
o
l
i
c
i
s
s
u
e
s
•
Chemical imbalance
–
Hyperkalemia
–
Metabolic acidosis
–
Hyperphosphatemia
–
Hyponatremia
•
“Uremic” symptoms
Conservative Management of
Established AKI: Diuretics
•
Increase urine output
•
Improve fluid balance
•
Permit delivery of fluid to patient
–
Nutrition, other therapies
•
May augment loss of potassium
Do Diuretics Help in AKI?
Bagshaw CCM 2008 36(4)
8
n
o
n
-
r
a
n
d
o
m
i
z
e
d
s
t
u
d
i
e
s
6
r
a
n
d
o
m
i
z
e
d
s
t
u
d
i
e
s
2
.
B
u
t
n
o
i
m
p
r
o
v
e
m
e
n
t
i
n
c
l
i
n
i
c
a
l
o
u
t
c
o
m
e
s
1. Majority of
ICU patients
get diuretics
Management of Established AKI:
Pharmacotherapy
A
t
t
e
m
p
t
e
d
T
h
e
r
a
p
i
e
s
•
Diuretics
•
Mannitol
•
Dopamine
•
Fenoldopam
•
Glucocorticoids
•
Atrial natriuretic peptide
•
N-acetylcysteine (other
than contrast-induced AKI
D
e
f
i
n
i
t
i
v
e
T
h
e
r
a
p
i
e
s
•
Hmmmm . . . . .
Conservative Management of
Established AKI: Traditional Approach
•
Limit fluid intake
•
Limit input of retained substances
•
Augment losses (diuretics)
•
Try not to mess up
•
Wait and Hope
Kolff Rotating Drum
Kidney: 1940s
•
~20 meters of sausage casing (2.4m
2
)
•
Prime volume 2 liters
•
Clearance 140 – 170 ml/min
First 16 patients died
Goals of Renal Replacement
Therapy (RRT)
•
Restore fluid, electrolyte and metabolic
balance
•
Remove endogenous or exogenous
toxins as rapidly as possible
•
Permit needed therapy and nutrition
•
Limit complications
RRT Options in AKI
•
Hemodialysis, Peritoneal Dialysis, CRRT
–
Each has advantages & disadvantages
•
Modality choice guided by
–
Patient Characteristics
•
Disease/Symptoms
•
Hemodynamic stability
–
Goals of therapy
•
Fluid removal, electrolyte correction, or both
–
Availability, expertise and cost
Walters et. al. Pediatr Nephrol 2008
Time Remaining: 1:30
Blood Flow Rate: 300 ml/min
Dialysate Flow Rate: 500 ml/min
Ultrafiltration Rate: 0.3 L/hr
Total Ultrafiltrate: 1.5 L/hr
•
Blood perfuses
extracorporeal circuit
•
Machine mixes
dialysate on-line
•
High efficiency system
•
Requires vascular
access; anticoagulation
•
Technically complex
•
May be poorly tolerated
by critically ill patient
Hemodialysis
Peritoneal Dialysis
•
Sterile dialysate
introduced into
peritoneal cavity
through a catheter
•
Possibly better tolerated
•
Lots of pediatric
experience in chronic
setting
•
Low efficiency system
•
Risk for infection
Continuous Renal Replacement
Therapy (CRRT)
•
Common ICU modality
•
Technically similar to HD
–
SLOW: ?Better tolerated
by ICU patient?
–
CONTINUOUS: Preserve
metabolic stability;
maintain fluid balance for
oliguric patients who
require high daily input (IV
medications, parenteral
nutrition)
R
i
n
s
e
-
O
-
M
a
t
i
c
3
0
0
0
RRT for AKI:
Which Modality is Best?
Rabindranath et al., Cochrane Database of Systematic Reviews (2007)
No Difference in Survival
RRT for AKI:
Which Modality is Best?
Bunchman et al., Pediatr Nephrol (2001) 16:1067–1071
Years of study: 1992-1998
N=226; Mean age 6y; Mean wt 25kg
P<0.01 (HD vs other)
CJASN 2007 2:732-8
O
v
e
r
a
l
l
s
u
r
v
i
v
a
l
w
a
s
5
8
%
a
c
r
o
s
s
a
l
l
c
e
n
t
e
r
s
Impact of Volume Overload
“
V
o
l
u
m
e
O
v
e
r
l
o
a
d
i
s
t
h
e
E
n
e
m
y
”
Higher Dose: A Better Outcome?
Ronco, et al.
Lancet
2000
Group 1: 20ml/kg/hr
Group 2: 35ml/kg/hr
Group 3: 45ml/kg/hr
N=425
Intensity of Renal Replacement in AKI:
No Difference?
VA/NIH Acute Renal Failure Trial
Network, NEJM, 2008
RENAL Replacement
Therapy Study Investigators,
NEJM, 2009
High Dose of CRRT for
Pediatric Patients
*p=0.533
Gillespie, Pediatr Nephrol 2004
RRT: Effective But Not Perfect
S
t
r
e
n
g
t
h
s
•
Volume control
–
Fluid removal from
vascular compartment
•
Metabolic control
–
Electrolyte removal
–
Uremic retention
molecule removal
W
e
a
k
n
e
s
s
e
s
•
Adapted equipment
–
Nothing specific for
smaller children
•
No auto-feedback
–
Targets programmed by
provider
•
“Blunt” metabolic control
–
Hard to fine-tune
–
Does not effectively
address immune issues
A Dedicated Neonatal CRRT Machine?
•
Lines and filters to
limit extracorporeal
blood volume
•
Hardware and
software accurate for
low flows and low UF
volumes
•
Dedicated rather
than adapted
•
Safe and reliable
Summary
•
Current approach to AKI is supportive,
addressing issues after AKI established
•
PD, HD, and CRRT can all have a role
–
Clear ability to control volume
–
Evidence for metabolic control
•
Goals for dose in AKI remain unclear
•
New technology may offer opportunities
for broader application & improved care
Early dialysis with Kolff artificial kidney, Mt Sinai
Hospital, New York, 1948
Explore supportive therapies, stage-based management, natural history, and challenges in Acute Kidney Injury (AKI) along with conservative and pharmacotherapeutic approaches. Learn about the role of diuretics, considerations in established AKI management, and historical perspectives on kidney therapies like the Kolff Rotating Drum Kidney.
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Presentation Transcript
Pediatric Acute Kidney Injury: Supportive Therapies Jordan M. Symons University of Washington School of Medicine Seattle Children s Hospital
Stage-Based Management of AKI Kidney Intl Supplements (2012) 2: 19-36
Natural History of Acute Kidney Injury (AKI)
What Goes Wrong in AKI? Volume issues Volume overload Pulmonary edema Tissue edema Congestive heart failure Hypertension (+/-) Metabolic issues Chemical imbalance Hyperkalemia Metabolic acidosis Hyperphosphatemia Hyponatremia Uremic symptoms
Conservative Management of Established AKI: Diuretics Increase urine output Improve fluid balance Permit delivery of fluid to patient Nutrition, other therapies May augment loss of potassium
Do Diuretics Help in AKI?Bagshaw CCM 2008 36(4) 1. Majority of ICU patients get diuretics 8 non-randomized studies 2. But no improvement in clinical outcomes 6 randomized studies
Management of Established AKI: Pharmacotherapy Attempted Therapies Diuretics Mannitol Dopamine Fenoldopam Glucocorticoids Atrial natriuretic peptide N-acetylcysteine (other than contrast-induced AKI Definitive Therapies Hmmmm . . . . .
Conservative Management of Established AKI: Traditional Approach Limit fluid intake Limit input of retained substances Augment losses (diuretics) Try not to mess up Wait and Hope
Kolff Rotating Drum Kidney: 1940s
From Patient ~20 meters of sausage casing (2.4m2) Prime volume 2 liters Clearance 140 170 ml/min Back To Patient First 16 patients died
Goals of Renal Replacement Therapy (RRT) Restore fluid, electrolyte and metabolic balance Remove endogenous or exogenous toxins as rapidly as possible Permit needed therapy and nutrition Limit complications
RRT Options in AKI Hemodialysis, Peritoneal Dialysis, CRRT Each has advantages & disadvantages Modality choice guided by Patient Characteristics Disease/Symptoms Hemodynamic stability Goals of therapy Fluid removal, electrolyte correction, or both Availability, expertise and cost Walters et. al. Pediatr Nephrol 2008
Hemodialysis Blood perfuses extracorporeal circuit Machine mixes dialysate on-line High efficiency system Requires vascular access; anticoagulation Technically complex May be poorly tolerated by critically ill patient Time Remaining: 1:30 Blood Flow Rate: 300 ml/min Dialysate Flow Rate: 500 ml/min Ultrafiltration Rate: 0.3 L/hr Total Ultrafiltrate: 1.5 L/hr
Peritoneal Dialysis Sterile dialysate introduced into peritoneal cavity through a catheter Possibly better tolerated Lots of pediatric experience in chronic setting Low efficiency system Risk for infection Dialysate Peritoneal Space Effluent Collection
Continuous Renal Replacement Therapy (CRRT) Common ICU modality Technically similar to HD SLOW: ?Better tolerated by ICU patient? CONTINUOUS: Preserve metabolic stability; maintain fluid balance for oliguric patients who require high daily input (IV medications, parenteral nutrition)
RRT for AKI: Which Modality is Best? In-hospital mortality No Difference in Survival Rabindranath et al., Cochrane Database of Systematic Reviews (2007)
RRT for AKI: Which Modality is Best? Survival by Modality 100% Years of study: 1992-1998 N=226; Mean age 6y; Mean wt 25kg 90% 80% 70% P<0.01 (HD vs other) 60% 50% 81% 40% 30% 49% 20% 40% 10% 0% Hemofiltration (N=106) Peritoneal Dialysis (N=59) Hemodialysis (N=61) Bunchman et al., Pediatr Nephrol (2001) 16:1067 1071
Overall survival was 58% across all centers CJASN 2007 2:732-8
Impact of Volume Overload Foland JA et al: Crit Care Med 2004 Gillespie R et al: Pediatr Nephrol 2004 Sutherland et al: AJKD 2010 Volume Overload is the Enemy Goldstein SL et al: Pediatrics 2001 N=113*p=0.02; **p=0.01 Hazard Ratio 3.02 (1.50-6.10) Kaplan-Meier survival estimates, by percentage fluid overload category
Higher Dose: A Better Outcome? Hazard Ratio (95% CI) N=425 1 Group 1 Group 2 Group 3 0.51 (0.35-0.72) 0.49 (0.35-0.69) Group 1: 20ml/kg/hr Ronco, et al. Lancet 2000 Group 2: 35ml/kg/hr Group 3: 45ml/kg/hr
Intensity of Renal Replacement in AKI: No Difference? VA/NIH Acute Renal Failure Trial Network, NEJM, 2008 RENAL Replacement Therapy Study Investigators, NEJM, 2009
High Dose of CRRT for Pediatric Patients CRRT Dose N Survivors Hazard Ratio (95% CI)* Low Dose <25.6ml/kg/hr 43 23 0.810 (0.418-1.57) High Dose >25.6ml/kg/hr 44 17 1.23 (0.637-2.39) *p=0.533 Gillespie, Pediatr Nephrol 2004
RRT: Effective But Not Perfect Strengths Weaknesses Adapted equipment Nothing specific for smaller children No auto-feedback Targets programmed by provider Blunt metabolic control Hard to fine-tune Does not effectively address immune issues Volume control Fluid removal from vascular compartment Metabolic control Electrolyte removal Uremic retention molecule removal
A Dedicated Neonatal CRRT Machine? Lines and filters to limit extracorporeal blood volume Hardware and software accurate for low flows and low UF volumes Dedicated rather than adapted Safe and reliable Claudio Ronco with the Cardio Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)
Summary Current approach to AKI is supportive, addressing issues after AKI established PD, HD, and CRRT can all have a role Clear ability to control volume Evidence for metabolic control Goals for dose in AKI remain unclear New technology may offer opportunities for broader application & improved care
Early dialysis with Kolff artificial kidney, Mt Sinai Hospital, New York, 1948
