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)
8 non-randomized studies
6 randomized studies
1. Majority of
ICU patients
get diuretics
2. But no
improvement
in clinical
outcomes
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
First 16 patients died
Back
To
Patient
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
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
Peritoneal Dialysis
• Sterile dialysate
introduced into
peritoneal cavity
through a catheter
Dialysate
• Possibly better tolerated
• Lots of pediatric
experience in chronic
setting
Peritoneal
Space
• Low efficiency system
• Risk for infection
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%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Years of study: 1992-1998
N=226; Mean age 6y; Mean wt 25kg
P<0.01 (HD vs other)
81%
40%
Hemofiltration
(N=106)
49%
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
2004SL et al: Pediatrics 2001
Goldstein
Gillespie **p=0.01
R et al: Pediatr Nephrol 2004
*p=0.02;
N=113
Sutherland et al: AJKD 2010
“Volume Overload is the Enemy”
Hazard Ratio
3.02 (1.50-6.10)
Kaplan-Meier survival estimates, by
percentage fluid overload category
Higher Dose: A Better Outcome?
N=425
Hazard Ratio
(95% CI)
Group 1
1
Group 2 0.51 (0.35-0.72)
Group 3 0.49 (0.35-0.69)
Group 1: 20ml/kg/hr
Group 2: 35ml/kg/hr
Group 3: 45ml/kg/hr
Ronco, et al. Lancet 2000
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
43
<25.6ml/kg/hr
High Dose
44
>25.6ml/kg/hr
23
0.810 (0.418-1.57)
17
1.23 (0.637-2.39)
*p=0.533
Gillespie, Pediatr Nephrol 2004
RRT: Effective But Not Perfect
Strengths
• Volume control
– Fluid removal from
vascular compartment
• Metabolic control
– Electrolyte removal
– Uremic retention
molecule removal
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
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