Renal Replacement
Therapy Options for
Children
Timothy E. Bunchman, MD
Professor & Director
Helen DeVos Children’s Hospital
Grand Rapids, MI
Timothy.bunchman@devoschildrens.org
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)


HD (intermittent)


Acute, CAPD, CCPD
Standard vs High Flux
CRRT (continuous)

CVVH, CVVHD, CVVHDF
Dialysis (diffusive)

PD vs. HD vs. CVVHD



Works with solute clearance across a semipermeable 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)
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)
*P<0.05 **P<0.01
adsorbed
minimal clearance
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
Urea Clearance
(mls/min/1.73 m2)
(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
10
9
8
7
6
5
4
3
2
1
0
35ml/kg
EDD
CRRT
20ml/kg
7
6
5
4
3
2
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
No. of Days/week
Weekly stdKt/V
45ml/kg
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
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
-
+
-
Percent of Patients (%)
PATIENT MORTALITY
N=21
N=9
Modality
Fleming et al., J Thorac
Cardiovasc Surg, 1995
(NS in mortality)
N=12
% Change From Baseline
CALORIC INTAKE
CAVH
*
CVVH *
PD
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
% Survival
P<0.01
P<0.01
Ped Neph 16:1067-1071, 2001
(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


Ease of administration at bedside


Chien et al Pediatr Neonatol 2009; 50:25-279
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
Number (%, 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)
The etiology of acute renal failureNigeria ( 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
Rebound
Time of therapy
Rx
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
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 nonrenal 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
Copyright restrictions may apply.
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
Copyright restrictions may apply.
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
Copyright restrictions may apply.
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 2472 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: 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