pediatric bone marrow transplant recipients with acute renal failure

Pediatric Bone Marrow Transplant Recipients with Acute Renal Failure

Pediatric Bone Marrow Transplant Recipients with Acute Renal Failure

Stuart L. Goldstein, MD

Assistant Professor of Pediatrics

Baylor College of Medicine

IntroductionIntroduction

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 PatientsCauses 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 ARFPediatric Studies of BMT Recipients with ARF

Lane et al (1994) (n=30)Sepsis most common cause of ARF and deathFactors 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 ARFPediatric 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 OverloadARF and Fluid Overload

BMT pts with ARF are at risk of FOPre-transplant conditioning can cause small vessel injury and extravascular fluid extravasation Need for large volume requirement– blood products – total parenteral nutrition– multiple antibiotics

Fluid OverloadFluid 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 UnitCurrent 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

% FO* =[ Fluid In (L) - Fluid Out (L) Pre BMT Weight (kg) ] * 100%

Fluid Overload

• Fluid In = Total Input in Liters Since Admission for BMT

• Fluid Out = Total Output in Liters Since Admission for BMT

ObjectiveObjective

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

MethodsMethods 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

ResultsResults

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


ResultsResults

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


ResultsResults ARF Characteristics

Etiology – Acute tubular necrosis (n=1)– Nephrotoxic meds (n=16)– ATN/Septic shock+Nephrotoxicity (n=9)

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


ResultsResults

ICU Characteristics23/26 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


ResultsResults

Patient Outcome11/26 (46%) pts survived an initial ARF episodeAll 11 survivors were <10 %FO at ARF

resolution/RRT termination4/14 RRT (28%) treated patients survived– 2/3 HD (67%)– 2/11 CRRT (18%)


10 RRT 2 non-RRT

3 <10% FO 12 >10% FO

4 RRT (2 HD & 2 CVVHD)

All 4 re-attained <10% FO

7 remained >10%FO

3 re-attained <10%FO

11 (46%) survived 15 (54%) died

26 ARF pts

Patient Outcome:

4 >10% FO (max 12%)

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 StudyTCH 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


TCH BMT Study: ConclusionTCH 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


Stanford ICU/BMT/CRRT studyStanford ICU/BMT/CRRT study

10 patients with ARDS6 BMT, 3 chemotherapy, 1 hemophagocytosisSerum creatinine 0.2 to 1.2 mg/dL in six childrenSerum 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/hour13 +/- 9 days

DiCarlo JV et al: J Pediatr Hematol Oncol. 2003 25:801-5

Stanford ICU/BMT/CRRT studyStanford ICU/BMT/CRRT study 9/10 patients successfully extubated 8/10 patients survived

4/6 BMT patients survived4/4 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 DatappCRRT 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 CRRTSepsis (18%)Hepatorenal syndrome (14%)No single Dx (54%)

8/22 (36%) patients survivedFlores FX et al for the ppCRRT: 9th CRRT meeting, San Diego, March 2004

ppCRRT BMT Data: Clinical VariablesppCRRT BMT Data: Clinical Variables

15.5±2.816.14±2.25Initial Paw

10.64±2.3511.22±2.3Age (yrs)

67,384.79±12,997.8352,070.00±21,688.03Total ultrafiltration volume (ml)

1.68±0.35.09±3.61Urinary output (cc/kg/hr)

0.86±0.41.69±0.31Number of pressors

17.23±1.5713.75±1.89CVP (cm H2O)

61.52±14.463.77±9.21GFR

15.62±2.110.67±2.35Initial PRISM 2 score

26.3±2.86**11.2±1.85MAP at the end of CRRT

16.11±4.02*3.75±2.04FO at CRRT initiation (%)

8.57±1.664.25±0.62Mean CRRT duration (days)

15.08±9.9710.14±1.8Mean time between ICU admission andCRRT initiation (days)

Non-SurvivorsSurvivorsClinical Variables(mean±STD)

Flores FX et al for the ppCRRT: 9th CRRT meeting, San Diego, March 2004*p<0.05, **p<0.01

CRRT for Pediatric BMT SummaryCRRT 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

pediatric bone marrow transplant recipients with acute renal failure

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