Pediatric Bone Marrow Transplant Recipients with Acute Renal Failure

1
Pediatric Bone Marrow Transplant Recipients with
Acute Renal Failure

• Stuart L. Goldstein, MD
• Assistant Professor of Pediatrics
• Baylor College of Medicine

2
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
3
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

4
Pediatric Studies of BMT Recipients with ARF

• Lane et al (1994) (n30)
• Sepsis most common cause of ARF and death
• Factors associated with persistent renal failure
• gt 10 Fluid Overload (FO)
• gt 3 pressors
• Hyperbilirubinemia
• Todd et al (1994) (n54)
• Increased mortality
• Multiple organ system failure
• Primary pulmonary parenchymal disease

5
Pediatric Studies of BMT Recipients with ARF

• Bunchman et al (2001) (n26)
• 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

6
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

7
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

8
Current Practice at TCH BMT Unit

• TCH Renal/BMT ARF protocol developed (Jan99) 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 gt 10 FO and
• 50 rise in serum creatinine or
• 50 decrease in daily urine output

9
Fluid Overload


Fluid In (L) - Fluid Out (L) Pre BMT Weight
(kg)
FO
100

• Fluid In Total Input in Liters Since Admission
  for BMT
• Fluid Out Total Output in Liters Since
  Admission for BMT

10
Objective

• To determine if prevention of severe fluid
  overload improves outcome in pediatric patients
  with BMT and ARF

11
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 Fishers
  exact test)
• p-value lt0.05 significant

Michael M Ped Neph 2004 1991-5
12
Results

• Patient Characteristics
• 272 pts received allogeneic BMT
• All received chemo/radio therapy for
  pre-transplant conditioning and GVHD prophylaxis
• Underlying diseases AML, ALL, aplastic anemia,
  CML, NHL, HL, VAHS, leukodystrophy and
  myelodysplastic syndrome

Michael M Ped Neph 2004 1991-5
13
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 1991-5
14
Results

• ARF Characteristics
• Etiology
• Acute tubular necrosis (n1)
• Nephrotoxic meds (n16)
• ATN/Septic shockNephrotoxicity (n9)
• Renal function
• Mean baseline Cr 0.62 0.36 mg/dl
• Mean peak Cr 3.51 1.62 mg/dl
• Mean lowest GFRest 30.5 13.5 ml/min/1.73m2

Michael M Ped Neph 2004 1991-5
15
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 1991-5
16
Results

• Patient Outcome
• 11/26 (46) pts survived an initial ARF episode
• All 11 survivors were lt10 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 1991-5
17
(No Transcript)
18
Summary of Survival and Non-survival Data
19
TCH BMT Study

• All patients who remained gt10 FO despite
  starting RRT died
• All survivors maintained or re-attained lt10 FO
• Mechanical ventilation and PRISM score gt10 at ICU
  admission correlated with patient death
• Despite prospective intention to prevent severe
  FO, survival was lt50 in pediatric BMT patients
  with ARF

Michael M Ped Neph 2004 1991-5
20
TCH BMT Study Conclusion

• Maintenance or re-attainment of lt 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 1991-5
21
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
25801-5
22
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
25801-5
23
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
24
ppCRRT BMT Data Clinical Variables
plt0.05, plt0.01
Flores FX et al for the ppCRRT 9th CRRT meeting,
San Diego, March 2004
25
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