Transcript Pediatric Bone Marrow Transplant (BMT) Recipients with Acute

Pediatric Bone Marrow Transplant Recipients
with Acute Renal Failure
Stuart L. Goldstein, MD
Assistant Professor of Pediatrics
Baylor College of Medicine
Introduction
 Acute Renal Failure (ARF) is a common
complication in patients with BMT
 ARF in adult BMT pts: 30-80%
 ARF in pediatric 66 BMT pts: 21%*
11% with CRF 1yr post BMT
*Kist-van Holthe JE et al, Ped Neph (2002), 17(12): 1032-1037
Causes of ARF in BMT Patients

ARF is usually multi-factorial
Early ARF (0 to 60 days)
– Acute tubular necrosis (ATN)
– Veno-occlusive disease (VOD)
– Septic shock
– Nephrotoxic medications
Late onset ARF (3 to 12 months)
– Cyclosporine toxicity
– Radiotherapy-induced nephropathy
Pediatric Studies of BMT Recipients with ARF

Lane et al (1994) (n=30)
Sepsis most common cause of ARF and death
Factors associated with persistent renal failure
– > 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
ARF and Fluid Overload
 BMT pts with ARF are at risk of FO
Pre-transplant conditioning can cause small
vessel injury and extravascular fluid
extravasation
Need for large volume requirement
– blood products
– total parenteral nutrition
– multiple antibiotics
Fluid Overload
 Goldstein et al
(2001) reported in a review of
critically ill children who received CRRT
Increasing degrees of FO prior to initiation of
CRRT was associated with greater mortality
Postulated early initiation of CRRT prior to
development of FO might lead to improved
outcome
Current Practice at TCH BMT Unit
 TCH Renal/BMT ARF protocol developed
(Jan’99) for the prevention and treatment of
FO in BMT pts with ARF
 Pts at 5% FO are started on furosemide and
low-dose dopamine drips
 RRT/CRRT initiated at > 10% FO and
– 50% rise in serum creatinine or
– 50% decrease in daily urine output
Fluid Overload
%
FO*
[
=
]
Fluid In (L) - Fluid Out (L) * 100%
Pre BMT Weight (kg)
• Fluid In = Total Input in Liters Since Admission for BMT
• Fluid Out = Total Output in Liters Since Admission for BMT
Objective
 To determine if prevention of
severe fluid overload improves
outcome in pediatric patients with
BMT and ARF
Methods
 Retrospective chart review of all pts with BMT
and ARF from Jan 1999 – Jan 2002
 ARF: doubling of baseline serum creatinine
 Outcome measure: Survival at ARF
resolution/RRT termination
 Data analysis:
Non-parametric tests (chi-square or Fisher’s exact
test)
p-value <0.05 significant
Michael M: Ped Neph 2004 19:91-5
Results
 Patient Characteristics
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
Michael M: Ped Neph 2004 19:91-5
Results
 33 ARF episodes in 29 patients (11%)
 Excluded ARF episodes:
4 second ARF episodes (100% mortality)
3 patients with non-oliguric ARF
 26 initial oliguric ARF episodes analyzed
Mean patient age 13 + 5 years (2-23.5)
Mean days to ARF after BMT: 28 + 29 days (2-90); 4
pts had ARF at 60-90 days
Michael M: Ped Neph 2004 19:91-5
Results
 ARF Characteristics
Etiology
– Acute tubular necrosis (n=1)
– Nephrotoxic meds (n=16)
– ATN/Septic shock+Nephrotoxicity (n=9)
Renal function
– Mean baseline Cr:
– Mean peak Cr:
– Mean lowest GFRest:
Michael M: Ped Neph 2004 19:91-5
0.62 + 0.36 mg/dl
3.51 + 1.62 mg/dl
30.5 + 13.5 ml/min/1.73m2
Results
 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
Michael M: Ped Neph 2004 19:91-5
Results
 Patient Outcome
11/26 (46%) pts survived an initial ARF
episode
All 11 survivors were <10 %FO at ARF
resolution/RRT termination
4/14 RRT (28%) treated patients survived
– 2/3 HD (67%)
– 2/11 CRRT (18%)
Michael M: Ped Neph 2004 19:91-5
Patient Outcome:
26 ARF pts
11 (46%) survived
7 remained
<10% FO
15 (54%) died
4 >10% FO
(max 12%)
3 <10% FO
12 >10% FO
10 RRT
2 non-RRT
4 RRT (2 HD & 2 CVVHD)
All 4 re-attained
<10% FO
3 re-attained
<10%FO
7 remained
>10%FO
Summary of Survival and Non-survival Data
Clinical
Variables
Survival
Non-Survival p value
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%)
0.0687
Sepsis
7/11 (63%)
13/15 (86%)
0.1685
RRT treated
4/11 (36%)
10/15 (66%)
0.1257
TCH BMT Study
 All patients who remained >10% FO despite
starting RRT died
 All survivors maintained or 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
Michael M: Ped Neph 2004 19:91-5
TCH BMT Study: Conclusion
 Maintenance or re-attainment of < 10% fluid
overload is necessary but not sufficient for
survival of BMT pts with ARF
 Aggressive management with diuretics and
early initiation of RRT to prevent worsening
%FO may improve survival of these patients
Michael M: Ped Neph 2004 19:91-5
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)
3000 ml/1.73m2/hour
13 +/- 9 days
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
ppCRRT BMT Patient Data

22 patients January 2001 – December 2003)
Median age 9.45 years (range 2.2 - 23.5 years)

CRRT modalities
CVVHD (45%)
CVVH (41%)
CVVHDF (14%)

Diagnoses leading to CRRT
Sepsis (18%)
Hepatorenal syndrome (14%)
No single Dx (54%)

8/22 (36%) patients survived
Flores FX et al for the ppCRRT: 9th CRRT meeting, San Diego, March 2004
ppCRRT BMT Data: Clinical Variables
Clinical Variables
(mean±STD)
Survivors
Non-Survivors
Age (yrs)
11.22±2.3
10.64±2.35
Mean time between ICU admission and
CRRT initiation (days)
10.14±1.8
15.08±9.97
Mean CRRT duration (days)
4.25±0.62
8.57±1.66
FO at CRRT initiation (%)
3.75±2.04
16.11±4.02*
Initial Paw
16.14±2.25
15.5±2.8
MAP at the end of CRRT
11.2±1.85
26.3±2.86**
Initial PRISM 2 score
10.67±2.35
15.62±2.1
GFR
63.77±9.21
61.52±14.4
CVP (cm H2O)
13.75±1.89
17.23±1.57
Number of pressors
1.69±0.31
0.86±0.4
Urinary output (cc/kg/hr)
5.09±3.61
1.68±0.3
52,070.00±21,688.03
67,384.79±12,997.83
Total ultrafiltration volume (ml)
*p<0.05, **p<0.01
Flores FX et al for the ppCRRT: 9th CRRT meeting, San Diego, March 2004
CRRT for Pediatric BMT 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 BMT patients with
ARF
 Early hemofiltration may the inflammatory
response for intubated pediatric BMT patients