Download Pediatric Bone Marrow Transplant (BMT)

Pediatric Bone Marrow Transplant
Recipients with Acute Kidney Injury
Stuart L. Goldstein, MD
Associate Professor of Pediatrics
Baylor College of Medicine
Pediatric AKI Risk Factors:
Stem Cell Transplant Recipients

AKI in stem cell transplantation results from:
 Nephrotoxic
medications
 Radiation nephritis (post-SCT HUS)
 Veno-occlusive disease (hepatorenal syndrome)
 Sepsis

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Early pediatric study1 (1975-88) revealed 50%
AKI rate after SCT
Recent studies describe AKI epidemiology in
pediatric SCT with lower TBI doses
1. Van Why SK et al: Bone Marrow Transplant 7:383, 1991
AKI in SCT Patients: Timing

Early AKI (0 to 60 days)
 Acute
tubular necrosis (ATN)
 Veno-occlusive disease (VOD)
 Septic shock
 Nephrotoxic medications

Late onset AKI (3 to 12 months)
 Cyclosporine/tacrolimus
 Radiation
 Sepsis
nephritis
toxicity
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Prospective single center study of 66 patients
who received SCT over a 2 year period
AKI defined as SCr doubling in first 3 months
Cyclosporine given to 60 patients
 IV
(2 mg/kg/dose) for 30 days
 Orally (6 mg/kg/day) 3-6 months
 200 pg/ml target level
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21% AKI rate
Conditioning regimen nor
malignancy associated
with AKI
VOD, CYA trough >200,
foscarnet use associated
with AKI development
AKI associated with CKD
development (OR 8.0) at
one year
Pediatric SCT Recipients with AKI

Lane et al (1994) (n=30)
 Sepsis
most common cause of AKI and death
 Factors associated with persistent renal failure

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> 10% Fluid Overload (%FO)
> 3 pressors
Hyperbilirubinemia
Todd et al (1994) (n=54)
 Increased mortality
 Multiple organ system failure
 Primary pulmonary parenchymal disease
Pediatric Studies of BMT Recipients
with ARF
 Bunchman
et al (2001) (n=26)
BMT
pts with ARF requiring RRT had
42% survival rate

Greater survival for those required only HD
(78%) compared to PD (33%) or HF (21%)
Outcome
of children requiring RRT
directly related to the underlying
diagnosis as well as their requirement
for pressors
Retrospective evaluation of 226 children
who received RRT for AKI from 1992-1998
 26 patients with SCT
 Pressor use surrogate marker for patient
severity of illness
 Survival defined at PICU discharge

AKI and Fluid Overload

SCT pts with AKI are at risk for serious
sequlae of FO
 Pre-transplant
conditioning causes small
vessel injury and extravascular fluid
extravasation
 Need for large volume requirement
blood products
 total parenteral nutrition
 multiple antibiotics

[
% FO at CVVH initiation =
Fluid In - Fluid Out
ICU Admit Weight
]
* 100%
Fluid In = Total Input from ICU admit to CRRT initiation
Fluid Out = Total Output from ICU admit to CRRT initiation

Lesser % FO at CVVH (D)
initiation was associated with
improved outcome (p=0.03)
Lesser % FO at CVVH (D)
initiation was also associated
with improved outcome when
sample was adjusted for
severity of illness (p=0.03;
multiple regression analysis)
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%FOatCVVHInitiation
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Seven center study from
the ppCRRT Registry
116 patients with MODS
PRISM 2 score used to
assess patient severity of
illness
Survival defined at PICU
discharge

Retrospective single center review of SCT
patient AKI fluid/RRT management algorithm
 Furosemide infusion at 5%
 RRT at 10% fluid overload


fluid overload
AKI defined as doubling of SCr or >10% FO
from hospital admission
29 patients with 32 AKI episodes in 272 SCTs
patients with 2nd AKI (all died)
patient with pre-renal azotemia
 3 patients with non-oliguric AKI
 First AKI rate of 11%
4
1

272 pts received allogeneic BMT
 All
received chemo/radio therapy for pretransplant conditioning and GVHD
prophylaxis
 Underlying diseases: AML, ALL, aplastic
anemia, CML, NHL, HL, VAHS,
leukodystrophy and myelodysplastic
syndrome

AKI Characteristics
 Etiology
Acute tubular necrosis (n=1)
 Nephrotoxic meds (n=16)
 ATN/Septic shock+Nephrotoxicity (n=9)

 Kidney
function
Mean baseline Cr:
 Mean peak Cr:
 Mean lowest GFRest:
ml/min/1.73m2

0.62 + 0.36 mg/dl
3.51 + 1.62 mg/dl
30.5 + 13.5

ICU Characteristics
 23/26
with ICU admission
 Mean Pediatric risk mortality (PRISM) score
10.5 + 5 (5-20)
 Mean maximum % FO : 9 + 5% (3 -18%)
 14/26 with renal replacement therapy (RRT)
11/14 received CRRT
 3/14 received intermittent HD

Clinical Variables
Survival
Non-Survival
p
Always <10% FO
7/11 (64%)
3/15 (20%)
< 0.03
Ventilation
6/11 (55%)
14/15 (93%)
< 0.05
PRISM score >10
2/8 (25%)
11/15 (73%)
< 0.05
Pressor >1
2/11 (18%)
8/15 (53%)
0.07
Sepsis
7/11 (63%)
13/15 (86%)
0.17
RRT treated
4/11 (36%)
10/15 (66%)
0.13
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All patients who remained >10% FO despite
starting RRT died
All survivors maintained/re-attained <10% FO
Mechanical ventilation and PRISM score >10
at ICU admission correlated with patient death
Despite prospective intention to prevent
severe FO, survival was <50% in pediatric
BMT patients with ARF

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51/370 patients in the ppCRRT with SCT
28/51 male
AKI/CRRT causes
 Multi-factorial
(33%)
 Respiratory (18%)
 Sepsis (16%)
 VOD (16%)
 MODS (12%)
 Nephrotoxins (8%)
Non-survivors succumbing to primary pulmonary process and not excessive FO?
Patients requiring ventilatory support has
lower survival (13/37 vs. 10/14, p<0.05)
 Patients with MODS had nearly two-fold
increase in mortality
 Patients who received some convective
CRRT had improved survival (17/29
versus 6/22, p<0.05)

Stanford ICU/BMT/CRRT study

10 patients with ARDS
6
BMT, 3 chemotherapy, 1 hemophagocytosis
 Serum creatinine 0.2 to 1.2 mg/dL in six children
 Serum creatinine 1.7 to 2.4 mg/dL in four children

CVVHDF initiated coincident with intubation
regardless of fluid status or renal function (one
exception)
ml/1.73m2/hour
 13 +/- 9 days
 3000
DiCarlo JV et al: J Pediatr Hematol Oncol. 2003 25:801-5
Stanford ICU/BMT/CRRT study
9/10 patients successfully extubated
 8/10 patients survived

 4/6
BMT patients survived
 4/4 Chemotherapy patients survived

Conclusion: early initiation of
hemofiltration for intubated BMT patients
may prevent progressive inflammatory
lung injury and/or worsening fluid overload
DiCarlo JV et al: J Pediatr Hematol Oncol. 2003 25:801-5
CRRT for Pediatric SCT Summary
Most studies still demonstrate poor
survival for this population
 Early initiation of CRRT and aggressive
diuresis to prevent fluid overload seems to
be necessary, but not sufficient for
pediatric SCT patients with AKI
 Early CRRT may blunt the inflammatory
response and prevent need for intubation
or increase likelihood of extubation
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