renal replacement therapy options for children timothy e. bunchman, md professor & director...
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Renal Replacement Therapy Options for
ChildrenTimothy E. Bunchman, MD
Professor & Director Helen DeVos Children’s Hospital
Grand Rapids, MI
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
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 Clearance
CVVHDF Convective clearance
Replacement Solutions Diffusive clearance
Dialysis solution
Convective and Diffusive Clearance
Sieving Coefficients
Solute (MW) Convective Coefficient Diffusion Coefficient
Urea (60) 1.01 ± 0.05 1.01 ± 0.07
Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06
Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04*
Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04**
Calcium (protein bound) 0.67 + 0.1 0.61 + 0.07
Cytokines (large) adsorbed 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)
U
rea C
leara
nce
(mls
/min
/1.7
3 m
2)
BFR = 4 mls/kg/minFRF/Dx FR = 2 l/1.73 m2/hrSAM = 0.3 m2
p = NS
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
0123456789
10W
eekly
std
Kt/
V
0.3 0.5 0.7 0.9 1.1 1.3 1.5
eKt/V each dialysis
234567
No. o
f Days/w
eek
EDDEDD
35ml/kg35ml/kg
45ml/kg45ml/kg
20ml/kg20ml/kg
Adapted from Gotch et al. Kidney Int 2000;58:S3-18Adapted from Gotch et al. Kidney Int 2000;58:S3-18
CRRTCRRT
PD
Dialysis Dose and OutcomeRonco 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
425 patientsEndpoint = survival 15 days after D/C HF
146 UF rate 20ml/kg/hrsurvival significantly lower
in this group compared to the others
139 UF rate 35ml/kg/hrp=0.0007
140 UF rate 45ml/kg/hrp=0.0013
Relative Advantages (+) and Disadvantages (-) of CRRT, IHD, and PD
Variable CRRT IHD PD-----------------------------------------------------------------------------
-----------------
Continuous RRT + - +
Hemodynamic stability + - +
Fluid balance achievement + - -
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 ± - +
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 MORTALITYP
erce
nt
of P
atie
nts
(%
)
Modality
(NS in mortality)
N=21 N=9 N=12
Fleming et al., J Thorac Cardiovasc Surg, 1995
CALORIC INTAKE
PD
CAVH *
CVVH *
Fleming et al., J Thorac Cardiovasc Surg, 1995
% C
han
ge F
rom
Bas
elin
e
Modality(* p < 0.05 compared to PD)
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
% S
urvi
val
Ped Neph 16:1067-1071, 2001
P<0.01
P<0.01
(ns)
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)
EtiologyNumber (%, N=211)
Gastroenteritis 61 (28.9)
Septicaemia 32 (15.2)
With Tetanus 4 (5.3)
Acute glomerulonephritis 29 (13.7)
Plasmodium falciparum malaria 29 (13.7)
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 4
Renal vein thrombosis 1 (0.5)
211 Patients with ARF over an 18 year period
Dialysis indicated in 108 patientsOnly 24 had PD– due to resource
availability and costPrimary causes of death-
uremia, infection, anemia, hypertension and
LACK of Dialysis
The etiology of acute renal failure- Nigeria ( Anochie & Eke Peds Neph 2005:20 1610-1614)
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
Time of therapy
Vanc
level
(m
ic/d
l)
Rx Rx Rx
Rebound Rebound
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
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
Enrollment, Randomization, and Follow-up of Study Patients
Intensive vs Conventional
The VA/NIH Acute Renal Failure Trial Network. N Engl J Med 2008;359:7-20
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
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.
Copyright restrictions may apply.
Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560
Flow chart of the SHARF 4 study
Copyright restrictions may apply.
Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560
Outcome in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy
Copyright restrictions may apply.
Lins, R. L. et al. Nephrol. Dial. Transplant. 2009 24:512-518; doi:10.1093/ndt/gfn560
Survival curves in patients randomized to intermittent (IRRT) or continuous (CRRT) renal replacement therapy investigating ICU mortality and hospital
mortality
Cost of Dialysis Equipment (in U.S. dollars)
Manual Peritoneal Dialysis
Device: Dialy-Nate Manual PD setManufacturer: Utah Medical
ProductsCost per Unit: $88.75 (New set Required
every 24-72 h)
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: BaxterCost 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 CyclerManufacturer: FreseniusCost per unit: $12,295.00Cost of additional supplies:
Pediatric Tubing set $32.00 each
Cost of Dialysis Equipment (in U.S. dollars) cont.
Intermittent Hemodialysis
Device: C3Manufacturer: GambroCost per unit: $18,000.00Cost of additional Supplies: 100HG
dialyzer $50.00 each;pediatric bloodlines $11.40 each
Cost of Dialysis Equipment (in U.S. dollars) cont.
Continuous HemofiltrationDevice: PrismaManufacturer: GambroCost per unit: $25,000.00Cost 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