1. Renal Replacement Therapy Options for Children
Timothy E. Bunchman, MD
Professor & Director
Helen DeVos Children’s Hospital
Grand Rapids, MI

2. Questions?
Is there an optimal form of RRT in children independent of cause of AKI?
Are there studies comparing outcome randomized by RRT modality in children?

3. RRT Options (all are reasonable to use)
PD (continuous or intermittent)
Acute, CAPD, CCPD
HD (intermittent)
Standard vs High Flux
CRRT (continuous)
CVVH, CVVHD, CVVHDF

4. Dialysis (diffusive) PD vs. HD vs. CVVHD
Works with solute clearance across a semi-permeable membrane
The greater the gradient the greater the clearance
The greater the solution exposure per unit of time the greater the clearance

5. Diffusive Clearance CVVHD/HD/PD Diffusive clearance Dialysate
Physiologic sterile solution that is infused countercurrent to the blood flow rate (Qd)

6. Replacement (Convective)
Due to mass transfer (push) of solute thru a semi-permeable membrane
The pore size of the membrane may effect clearance
AN-69 membrane > Polysulphone
The greater the solution exposure per unit of time the greater the clearance

7. Convective Clearance CVVH Convective clearance Replacement Solutions
Physiologic sterile solution that is either infused pre filter (NA) or post filter (outside of NA) that infused at a set rate (Qr)

8. Convective and Diffusive Clearance
CVVHDF
Convective clearance
Replacement Solutions
Diffusive clearance
Dialysis solution

9. Sieving Coefficients
Solute (MW) Convective Coefficient Diffusion Coefficient
Urea (60) 1.01 ± ± 0.07
Creatinine (113) 1.00 ± ± 0.06
Uric Acid (168) 1.01 ± ± 0.04*
Vancomycin (1448) 0.84 ± ± 0.04**
Calcium (protein bound)
Cytokines (large) adsorbed minimal clearance
*P< **P<0.01

10. Impact of urea Clearance CVVH vs CVVHD (Maxvold et al, Crit Care med
Impact of urea Clearance CVVH vs CVVHD (Maxvold et al, Crit Care med Apr;28(4):1161-5)
Study design
Fixed blood flow rate-4 mls/kg/min
HF-400 (0.3 m2 polysulfone)
Cross over for 24 hrs each to prefilter replacement fluid (CVVH) or Dx (CVVHD) flow at 2000 mls/hr/1.73 m2

11. Comparison of Urea Clearance: CVVH vs CVVHD (Maxvold et al, Crit Care med. 2000 Apr;28(4):1161-5)
p = NS
(mls/min/1.73 m2)
Urea Clearance
BFR = 4 mls/kg/min
FRF/Dx FR = 2 l/1.73 m2/hr
SAM = 0.3 m2

12. Solute clearance vs UF Solute Clearance/unit of time
HD > HF > PD
(30-50 l/hr vs 2 l/hr vs 1-2 /hr Dx)
UF with regard to hemodyamics
HF > PD > HD
(24 hrs/day vs 3-4 hrs/day or QO Day)

13. Dialysis Dose Adapted from Gotch et al. Kidney Int 2000;58:S3-18 1 2 3
35ml/kg
45ml/kg
20ml/kg
CRRT 1 2 3 4 5 6 7 8 9 10 2 3 4 5 6 7
EDD
Weekly stdKt/V
No. of Days/week PD
0.3
0.5
0.7
0.9
1.1
1.3
1.5
eKt/V each dialysis
Adapted from Gotch et al. Kidney Int 2000;58:S3-18

14. Dialysis Dose and Outcome Ronco et al. Lancet 2000; 351: 26-30
Conclusions:
Minimum UF rates should be ~ 35 ml/kg/hr
Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

15. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD, and PD
Variable CRRT IHD PD
Continuous RRT
Hemodynamic stability
Fluid balance achievement

16. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD, and PD
Variable CRRT IHD PD
Unlimited nutrition
Superior metabolic control
Continuous removal of toxins
Simple to perform ±

17. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont.
Variable CRRT IHD PD
Stable intracranial pressure
Rapid removal of poisons
Limited anticoagulation /

18. Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont.
Variable CRRT IHD PD
Intensive care nursing support
Hemodialysis nursing support ±
Patient mobility

19. Percent of Patients (%) Fleming et al., J Thorac Cardiovasc Surg, 1995
PATIENT MORTALITY
Percent of Patients (%)
N=21
N=9
N=12
Modality
(NS in mortality)
Fleming et al., J Thorac Cardiovasc Surg, 1995

20. Modality(* p < 0.05 compared to PD)
CALORIC INTAKE
% Change From Baseline
CAVH *
CVVH * PD
Modality(* p < 0.05 compared to PD)
Fleming et al., J Thorac Cardiovasc Surg, 1995

21. Renal Replacement Therapy in the PICU Pediatric Outcome Literature
122 children studied
No PRISM scores
Most common diagnosis
IHD: primary renal failure
CRRT: sepsis
31% survival
Conclusion: patients who receive CRRT are more ill
Maxvold NJ et al: Am J Kidney Dis 1997 Nov;30(5 Suppl 4):S84-8

22. Pediatric ARF: Modality and Survival
(ns)
Ped Neph 16: , 2001

23. Pediatric ARF: Modality and Survival
Patient survival on pressors (35%) lower than without pressors (89%) (p<0.01)
Lower survival seen in CRRT than in patients who received HD for all disease states
Ped Neph 16: , 2001

24. Unique Situations-PD Infants and Post Op Hearts Limited resources
Ease of fluid management
Chien et al Pediatr Neonatol 2009; 50:25-279
Ease of administration at bedside
Bonillis-Felix PDI S
Limited resources

25. The etiology of acute renal failure- Nigeria
( Anochie & Eke Peds Neph 2005: )
Etiology
Number (%, N=211)
Gastroenteritis
61 (28.9)
Septicaemia
32 (15.2)
With Tetanus
4 (5.3)
Acute glomerulonephritis
29 (13.7)
Plasmodium falciparum malaria
Birth asphyxia
27 (12.8)
Haemolytic uraemic syndrome
7 (3.3)
Malignancy
6 (2.8)
Leukaemia 4
Burkitt lymphoma 2
HIV related
3 (1.4)
Congenital malformation
10 (4.7)
Posterior urethral valves 6
Renal agenesis
Renal vein thrombosis
1 (0.5)

26. The etiology of acute renal failure- Nigeria ( Anochie & Eke Peds Neph 2005:20 1610-1614)
211 Patients with ARF over an 18 year period
Dialysis indicated in 108 patients
Only 24 had PD– due to resource availability and cost
Primary causes of death- uremia, infection, anemia, hypertension and
LACK of Dialysis

27. Unique Situations-HD (+/- CRRT)
Conditions when maximal solute clearance is needed with less concern on hemodynamic stability
Auron and Brophy
Current opinions in Pediatrics :
Quan and Quigley
Current opinions in Pediatrics :

28. Vancomycin clearance High efficiency dialysis membraneRx Rx Rx
Rebound
Rebound
Vanc level
(mic/dl)
Time of therapy

29. Unique Situations-CRRT
When hemodynamic instability and highly catabolic conditions are present
Sepsis
Bone Marrow Transplantation
Goldstein SL Seminars in Dialysis 2009; 22;
Walters et al Pediatr Neph ; 37-38

30. Stem Cell Transplant: ppCRRT
51 patients in ppCRRT with SCT
Mean %FO = %.
45% survival
Convection: 17/29 survived (59%)
Diffusion: 6/22 (27%), p<0.05
Survival lower in MODS and ventilated patients
Flores FX et al: Pediatr Nephrol Apr;23(4):625-30

31. Intensive vs non Intensive RRT
HD and CRRT at 6 days per week and 35 mls/kg/hr daily
Vs.
HD and CRRT at 3 days per week and 20 mls/kg/hr daily
Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury The VA/NIH Acute Renal Failure Trial Network*
NEJM july 3, 2008 vol. 359 no. 1

32. Enrollment, Randomization, and Follow-up of Study Patients
Figure 1. Enrollment, Randomization, and Follow-up of Study Patients.
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20

33. Intensive vs Conventional

34. Primary and Secondary Outcomes
Table 3. Primary and Secondary Outcomes.
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20

35. Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B)
Figure 2. Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B). Panel A shows the cumulative probability of death from any cause in the entire study cohort. Panel B shows odds ratios (and 95% confidence intervals [CI]) for death from any cause by 60 days in the group receiving the intensive treatment strategy as compared with the group receiving the less-intensive treatment strategy, as well as P values for the interaction between the treatment group and baseline characteristics. P values were calculated with the use of the Wald statistic. Higher Sequential Organ Failure Assessment (SOFA) scores indicate more severe organ dysfunction. There was no significant interaction between treatment and subgroup variables, as defined according to the prespecified threshold level of significance for interaction (P=0.10). Sex was not recorded for one patient receiving less-intensive therapy.
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20

36. Summary of Complications Associated with Study Therapy
Table 4. Summary of Complications Associated with Study Therapy.
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20

37. Conclusion of ATN Study
Intensive renal support in critically ill patients with AKI did not decrease mortality, improve recovery of kidney function, or reduce the rate of non-renal organ failure as compared with less-intensive therapy involving a defined dose of IHD three times per week and CRRT at 20 ml per kilogram per hour.

38. Flow chart of the SHARF 4 study
Lins, R. L. et al. Nephrol. Dial. Transplant : ; doi: /ndt/gfn560
Copyright restrictions may apply.

39. Outcome in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy
Lins, R. L. et al. Nephrol. Dial. Transplant : ; doi: /ndt/gfn560
Copyright restrictions may apply.

40. Survival curves in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy investigating ICU mortality and hospital mortality
Lins, R. L. et al. Nephrol. Dial. Transplant : ; doi: /ndt/gfn560
Copyright restrictions may apply.

41. Cost of Dialysis Equipment (in U.S. dollars)
Manual Peritoneal Dialysis
Device: Dialy-Nate Manual PD set
Manufacturer: Utah Medical Products
Cost per Unit: $88.75 (New set Required every h)
Cost of additional Supplies: 1.5% Dineal (Baxter) $24.43/2.0L

42. Cost of Dialysis Equipment (in U.S. dollars) cont.
Manual Peritoneal Dialysis
Device: Ultra Set (Y-set)
Manufacturer: Baxter
Cost per unit: $6.95 (New unit required for each exchange)
Cost of additional Supplies: 1.5% Dianeal (Baxter) $24.43/2.0L

43. Cost of Dialysis Equipment (in U.S. dollars) cont.
Automated Peritoneal Dialysis
Device: Freedom Cycler
Manufacturer: Fresenius
Cost per unit: $12,295.00
Cost of additional supplies: Pediatric Tubing set $32.00 each

44. Cost of Dialysis Equipment (in U.S. dollars) cont.
Intermittent Hemodialysis
Device: C3
Manufacturer: Gambro
Cost per unit: $18,000.00
Cost of additional Supplies: 100HG dialyzer $50.00 each;
pediatric bloodlines $11.40 each

45. Cost of Dialysis Equipment (in U.S. dollars) cont.
Continuous Hemofiltration
Device: Prisma
Manufacturer: Gambro
Cost per unit: $25,000.00
Cost of additional supplies: M60 hemofilter set
(includes filter and bloodlines) $160.00
Normocarb dialysate concentrate
(Dialysis Solutions) $20.00/3.0L

46. Conclusion
RRT modality comparison shows that the dose of RRT and the choice of RRT may not effect survival
Indication to begin, end is still of question
Do what you do well and improve your care of patient with AKI