Cytokine and Soluble Fas Ligand Response in Children with Septic Acute Renal Failure ARF on CVVH

1
Cytokine and Soluble Fas Ligand Response in
Children with Septic Acute Renal Failure (ARF) on
CVVH

• Paden ML, Fortenberry JD, Rigby MR, Trexler AM,
• Heard ML, Rogers K
• Childrens Healthcare of Atlanta at Egleston
• Division of Pediatric Critical Care Medicine
• Emory University School of Medicine, Atlanta, GA
  USA

2
Sepsis and CRRT

• In septic adults, CRRT
• Improves hemodynamics (Kamijo Y. Intensive Care
  Med 200026(9)1355-9)
• Allows control of fluid balance
• Maximizes nutrition
• Improves survival with high flow ultrafiltration
  rate (Ronco C, Lancet 200035626-30)
• Cytokine removal postulated as the basis for
  these effects (Bellomo R, Contrib Nephrol
  2001132367-74)

3
Sepsis and CRRTPeak Concentration Hypothesis
Adapted from Ronco C, et al, Artif Organs 2003
4
Controversy in Sepsis and CRRT

• Previous adult studies question the ability for
  CRRT to lower cytokine levels
• Concentration ? activity
• Cytokine clearance in children has not been
  adequately studied

5
Fas/Soluble Fas Ligand (sFasL) System

• Apoptotic pathway in multiple tissues
• Fas in HUS induced renal failure (Masri C, et al.
  Am J Kidney Dis 200036(4)859-62.)
• Levels correlate with
• Development of oligoanuria
• Need for acute dialysis
• Decreased GFR at 1 year after injury
• sFasL in ARDS (Imay Y, et al. JAMA
  2003289(16)2104-12.)
• Significant correlation between changes in sFasL
  and changes in creatinine.

6
Hypothesis

• Convective clearance of IL-6, IL-8, IL-10, and
  sFasL occurs in pediatric patients with acute
  renal failure (ARF) treated with CVVH.

7
Study Design

• Enrollment of all patients on CVVH
• Acute renal failure
• Greater than 5 kg
• lt 18 years old
• Technique
• CVVH via Braun Diapact
• Citrate anticoagulation
• Ultrafiltration rate 35-45 cc/kg/hour
• Cytokines measured by cytometric bead array from
  BD Pharmagen
• Serial measurements of cytokines
• Pre-CVVH
• 12, 24, 48 hours on CVVH
• End of CVVH and 24 hours after

8
Study Design

• Bacterial septic shock defined as
• Vasopressor dependent
• Positive blood culture
• Compared values in children with bacterial septic
  shock/ARF to non-septic ARF patients

9
Results

• Septic Shock Patients

10
Results

• Non-septic ARF Patients

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Results
24 Hours off CVVH
End of CVVH
24 Hours
12 Hours
48 Hours
Pre-CVVH
12
Results
24 Hours off CVVH
End of CVVH
12 Hours
24 Hours
Pre-CVVH
48 Hours
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Absolute cytokine changes in septic shock/ARF
patients


p0.04
plt0.02
Log Concentration (pg/ml)
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Absolute cytokine changes in septic shock/ARF
patients
p0.132
p0.818
Log Concentration (pg/ml)
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IL-8 Percent Changes From Pre-CVVH Baseline




plt0.03


Non-septic ARF Patients
Septic ARF Patients
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Mean Percent Decrease in Septic Shock/ARF Patients
plt0.05


Septic ARF Patients
Non-septic ARF Patients
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Mean Percent Decrease in Septic Shock/ARF Patients
plt0.05


Septic ARF Patients
Non-septic ARF Patients
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Ultrafiltrate Cytokine Levels
Septic ARF Patients
Non-septic ARF Patients
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Ultrafiltrate Cytokine Levels
Non-septic ARF Patients
Septic ARF Patients
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sFasL Analysis
24 h off CVVH
End of CVVH
12 h
24 h
48 h
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sFasL Response

• sFasL concentration pre-CVVH was similar in
  Septic Shock/ARF and non-septic ARF patients
• Median 130 pg/ml (24-439)
• Levels did not significantly decrease with CVVH
  (p0.818)

22
Conclusions

• CVVH significantly removes both pro-inflammatory
  (IL-6, IL-8) and anti-inflammatory (IL-10)
  cytokines in pediatric septic shock/ARF vs.
  non-septic patients
• Absolute decrease
• Greater relative decrease in septic patients
  compared to non-septic ARF patients
• Convective clearance is likely mechanism
• sFasL concentration is not changed by CVVH

23
Implications

• Effects of decreasing cytokines remain uncertain
• Future studies to evaluate cytokine clearance
• Regular CVVH
• High Volume Hemofiltration
• Different filters
• Clinical outcome studies