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

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 Children’s Healthcare of Atlanta at Egleston Division of Pediatric Critical Care Medicine

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

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  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 Children’s 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 2000;26(9):1355-9) • Allows control of fluid balance • Maximizes nutrition • Improves survival with high flow ultrafiltration rate (Ronco C, Lancet 2000;356:26-30) • Cytokine removal postulated as the basis for these effects (Bellomo R, Contrib Nephrol 2001;132:367-74)

  3. Sepsis and CRRT:Peak 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 2000;36(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 2003;289(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 • < 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

  11. 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

  13. Absolute cytokine changes in septic shock/ARF patients * * p=0.04 p<0.02 Log Concentration (pg/ml)

  14. Absolute cytokine changes in septic shock/ARF patients p=0.132 p=0.818 Log Concentration (pg/ml)

  15. IL-8 Percent Changes From Pre-CVVH Baseline * * * * *p<0.03 * Non-septic ARF Patients Septic ARF Patients

  16. Mean Percent Decrease in Septic Shock/ARF Patients *p<0.05 * * Non-septic ARF Patients Septic ARF Patients

  17. Mean Percent Decrease in Septic Shock/ARF Patients *p<0.05 * * Non-septic ARF Patients Septic ARF Patients

  18. Ultrafiltrate Cytokine Levels Non-septic ARF Patients Septic ARF Patients

  19. Ultrafiltrate Cytokine Levels Non-septic ARF Patients Septic ARF Patients

  20. sFasL Analysis 24 h off CVVH End of CVVH 12 h 48 h 24 h

  21. 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 (p=0.818)

  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

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