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