Renal Replacement Therapy Options for Children

Timothy E. Bunchman, MD Professor & Director Helen DeVos Children’s Hospital Grand Rapids, MI [email protected]

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?

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

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

Diffusive Clearance

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

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

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)

Convective and Diffusive Clearance

   CVVHDF Convective clearance  Replacement Solutions Diffusive clearance  Dialysis solution

Sieving Coefficients

Solute (MW) Urea (60) Creatinine (113) Uric Acid (168) Vancomycin (1448) Calcium (protein bound) Cytokines (large) Convective Coefficient Diffusion Coefficient 1.01 ± 0.05

1.01 ± 0.07

1.00 ± 0.09

1.01 ± 0.04

1.01 ± 0.06

0.97 ± 0.04* 0.84 ± 0.10

0.67 + 0.1

adsorbed 0.74 ± 0.04** 0.61 + 0.07

minimal clearance *P<0.05 **P<0.01

Impact of urea Clearance CVVH vs CVVHD

(Maxvold et al, Crit Care med. 2000 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

Comparison of Urea Clearance: CVVH vs CVVHD

(Maxvold et al, Crit Care med. 2000 Apr;28(4):1161-5)

p = NS BFR = 4 mls/kg/min FRF/Dx FR = 2 l/1.73 m2/hr SAM = 0.3 m2

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)

Dialysis Dose

45ml/kg

10 9 8 7 3 2 1 0 6 5 4

20ml/kg

0.3

PD

0.5

35ml/kg

CRRT 0.7

0.9

1.1

eKt/V each dialysis 1.3

EDD

1.5

Adapted from Gotch et al. Kidney Int 2000;58:S3-18 7 6 5 4 3 2

Dialysis Dose and Outcome

Ronco et al. Lancet 2000; 351: 26-30 425 patients Endpoint = survival 15 days after D/C HF 146 UF rate 20ml/kg/hr survival significantly lower in this group compared to the others 139 UF rate 35ml/kg/hr p=0.0007

140 UF rate 45ml/kg/hr p=0.0013

• Conclusions: – Minimum UF rates should be ~ 35 ml/kg/hr – Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration

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

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

Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont.

Variable CRRT IHD PD --------------------------------------------------------------------------- ---------- Stable intracranial pressure + + Rapid removal of poisons + Limited anticoagulation -/+ + +

Relative Advantages (+) and Disadvantages (-) of CRRT, IHD and PD cont.

Variable --------------------------------------------------------------------------- ----------------- CRRT IHD PD Intensive care nursing support + + Hemodialysis nursing support ± + + Patient mobility + -

PATIENT MORTALITY

N=21 Fleming et al., J Thorac Cardiovasc Surg, 1995 N=9 Modality (NS in mortality) N=12

CALORIC INTAKE

PD CAVH * CVVH * Modality(* p < 0.05 compared to PD) Fleming et al., J Thorac Cardiovasc Surg, 1995

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

Pediatric ARF: Modality and Survival

P<0.01

P<0.01

(ns) Ped Neph 16:1067-1071, 2001

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 16:1067-1071, 2001

Unique Situations-PD

  Infants and Post Op Hearts  Ease of fluid management  Chien et al Pediatr Neonatol 2009; 50:25-279  Ease of administration at bedside  Bonillis-Felix PDI 2009 29 S183-185 Limited resources

The etiology of acute renal failure- Nigeria ( Anochie & Eke Peds Neph 2005:20 1610-1614)

Etiology

Gastroenteritis Septicaemia With Tetanus Acute glomerulonephritis Plasmodium falciparum malaria Birth asphyxia Haemolytic uraemic syndrome Malignancy Leukaemia Burkitt lymphoma HIV related Congenital malformation Posterior urethral valves Renal agenesis Renal vein thrombosis

Number (%, N=211)

61 (28.9) 32 (15.2) 4 (5.3) 29 (13.7) 29 (13.7) 27 (12.8) 7 (3.3) 6 (2.8) 4 2 6 4 3 (1.4) 10 (4.7) 1 (0.5)

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

Unique Situations-HD (+/ CRRT)

 Conditions when maximal solute clearance is needed with less concern on hemodynamic stability   Auron and Brophy  Current opinions in Pediatrics 2010 22: 283-188 Quan and Quigley  Current opinions in Pediatrics 2005 17: 205-209

Vancomycin clearance High efficiency dialysis membrane

Rx Rx Rx Rebound Rebound Time of therapy

Unique Situations-CRRT

 When hemodynamic instability and highly catabolic conditions are present   Sepsis Bone Marrow Transplantation  Goldstein SL Seminars in Dialysis 2009; 22; 180-184  Walters et al Pediatr Neph 2009 24; 37-38

Stem Cell Transplant: ppCRRT

    51 patients in ppCRRT with SCT Mean %FO = 12.41 + 3.7%. 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. 2008 Apr;23(4):625-30

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

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

Intensive vs Conventional

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

Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death at 60 Days, According to Baseline Characteristics (Panel B) The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20

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

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.

Flow chart of the SHARF 4 study Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560

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Outcome in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560

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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. 2009 24:512-518; doi:10.1093/ndt/gfn560

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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

72 h) (New set Required every 24 Cost of additional Supplies: 1.5% Dineal (Baxter) $24.43/2.0L

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

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

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

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

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