Pediatric Acute Kidney Injury: Supportive Therapies
Jordan M. Symons
University of Washington School of Medicine
Seattle Children’s Hospital
Stage-Based Management of AKIKidney 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
2. But no improvement in clinical outcomes
1. Majority of ICU patients get diuretics
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
• ~20 meters of sausage casing (2.4m2)• Prime volume 2 liters• Clearance 140 – 170 ml/min
From Patient
BackTo
PatientFirst 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 Space
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
EffluentCollection
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)
Rinse-O-Matic3000
RRT for AKI: Which Modality is Best?
In-hospital mortality
Rabindranath et al., Cochrane Database of Systematic Reviews (2007)
No Difference in Survival
RRT for AKI: Which Modality is Best?
Hemofiltration (N=106)
Peritoneal Dialysis (N=59)
Hemodialysis (N=61)0%
10%20%30%40%50%60%70%80%90%
100%
40% 49%
81%
Survival by Modality
Bunchman et al., Pediatr Nephrol (2001) 16:1067–1071
Years of study: 1992-1998N=226; Mean age 6y; Mean wt 25kg
P<0.01 (HD vs other)
CJASN 2007 2:732-8
Overall survival was 58% across all centers
Impact of Volume Overload
Mean+SEMean-SE
Mean
OUTCOME
%F
O a
t C
VV
H Initi
atio
n
0
5
10
15
20
25
30
35
40
45
Death Survival
p = 0.03
Goldstein SL et al: Pediatrics 2001
N=113*p=0.02; **p=0.01Foland JA et al: Crit Care Med 2004
Gillespie R et al: Pediatr Nephrol 2004
Kaplan-Meier survival estimates, by
percentage fluid overload category
Hazard Ratio
3.02 (1.50-6.10)
Sutherland et al: AJKD 2010“Volume Overload is the Enemy”
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
1
0.51 (0.35-0.72)
0.49 (0.35-0.69)
Group 1
Group 2
Group 3
Hazard Ratio
(95% CI)
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
44
43
N
1.23 (0.637-2.39)17High Dose
>25.6ml/kg/hr
0.810 (0.418-1.57)23Low Dose
<25.6ml/kg/hr
Hazard Ratio (95% CI)*SurvivorsCRRT Dose
*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 reliableClaudio 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