bunchman management of aki - cairopedneph.com
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Management of AKITimothy E. Bunchman Professor and Director
Pediatric Nephrology & TransplantationChildren’s Hospital of Richmond
Virginia Commonwealth Univ. School of [email protected]
Overview How do we define AKI What is the incidence/etiology of AKI Are there non dialytic interventions we
should consider to treat AKI Are there new RRT equipment on the horizon
Incidence of Pediatric AKI 227 cases in the years 84-91. Yorkshire UK
Incidence: 0.8/yr/100.000 total population neonate-infant: 19.7/yr/100.000 age related
population 1-4 years: 5.9/yr/100.000 age related
population 5-15 years: 1.5/yr/100.000 age related
population children: 3.9/yr/100.000 age related
population 1/5 of the adult incidence ICU was needed for half the children ARF is often a secondary event (eg sepsis)
Etiology of Pediatric AKI(Andreoli SP, Curr Opin in Pediatr, 14:183-188, 2002)
HUS Moghal et al, Clin Nephro 49:91-95, 1998
ARF with MOSF Secondary to underlying disease
Surgery for congenital heart disease Bone marrow tx Solid organ tx
Causes of AKI in ChildrenInvestigators Kandoth Arora Bunchman CombinedSetting Developing
Country/ReferralCenter
DevelopingCounty/ReferralCenter
DevelopedCountry/
Tertiary Center
Causes N (%) N (%) N (%) N (%)HUS 5 (10) 25 (31) 5 (3) 35 (13)Glomerulonephritis 13 (27) 18 (23) 31(11)“Intrinsic RenalDisease”
13 (27) 64 (44) 77 (28)
Urinary Obstruction 8 (17) 7 (9) 15 (5)Post-Operative 11 (14) 24 (16) 35 (13)Sepsis 3 (4) 25 (17) 28 (10)Ischemic/Pre-renal 9 (19) 14 (18) 23 (8)Organ/BM Transplant 19 (13) 19 (7)Miscellaneous 2 (3) 9 (6) 11 (4)
Total 48 80 146 274
Current Opinion in Pediatrics, April 1998
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 4Burkitt lymphoma 2HIV related 3 (1.4)Congenital malformation 10 (4.7)Posterior urethral valves 6Renal agenesis 4Renal vein thrombosis 1 (0.5)
Pediatric Modified RIFLE Criteria Estim ated CrCl Urine output R isk GFR decrease by 25% <0.5m l/kg/hour for 8 hours Injury GFR decrease by 50% <0.5m l/kg/hour for 16 hours
Failure GFR decrease by 75% or GFR<35m l/m in/1.73m 2
<0.3 m l/kg/hour for 24 hours or anuric for 12 hours
Loss Persistent ARF > 4 weeks End stage End Stage Renal D isease (>3 m onths)
Goldstein et al , KI 2007
Modified Pediatric RIFLE
Now validated in 3 additional Pediatric Studies
LIMITATIONS OF AKI CLASSIFICATION CRITERIA
pRIFLE AKIN KDIGO
• inconsistency in application• urinary output criteria o en excluded → loss of addi onal cases • exclusion of patients with elevated initial SCr• UO and sCr are late markers• Biomarkers…
Neonatal AKI definition Stage Serum Creatinine (SCr)
Urine output (UOP)**
0 No change in SCr or rise < 0.3 mg/dL > 1 ml/kg/hour
1SCr rise ≥ 0.3 mg/dl within 48 hrs orSCr rise ≥ 1.5- 1.9 X reference SCr* within 7d
> 0.5 and ≤ 1 ml/kg/hour
2 SCr rise ≥ 2 to 2.9 X reference SCr*> 0.3 and ≤ 0.5 ml/kg/hour
3SCr rise ≥ 3 X reference SCr * orSCr ≥ 2.5 mg/dl or Receipt of dialysis ≤ 0.3 ml/kg /hour
*reference value is lowest previous value**includes days #2-7 only (day of birth = day #1)
Biomarkers: AMI versus AKIPeriod Acute Myocardial
InfarctionAcute Kidney
Injury1960s LDH1970s CPK, myoglobin1980s CK-MB1990s Troponin T2000s Troponin I
Multiple Therapies50% ↓ Mortality
Period Acute Myocardial Infarction
Acute Kidney Injury
1960s LDH Serum creatinine1970s CPK, myoglobin Serum creatinine1980s CK-MB Serum creatinine1990s Troponin T Serum creatinine2000s Troponin I Serum creatinine
Multiple Therapies50% ↓ Mortality
Supportive CareHigh Mortality
Need early biomarkers of AKI for improved understanding, early treatment and better
outcomes
Biomarkers: AMI versus AKI
Urine NGAL as an Early AKI Biomarker after Cardiopulmonary Bypass
AKI = 50% or greater increase in serum creatinine from baseline
Mishra et al, Lancet 2005, 365:1231-1238
Dialysis Dose and OutcomeRonco et al. Lancet 2000; 351: 26-30
• Conclusions:– Minimum UF rates should be ~ 35 ml/kg/hr– Survivors had lower BUNs than non-survivors
prior to commencement of hemofiltration
425 patientsEndpoint = survival 15 days
after D/C HF
146 UF rate 20ml/kg/hrsurvival significantly lower
in this group compared to the others
139 UF rate 35ml/kg/hrp=0.0007
140 UF rate 45ml/kg/hrp=0.0013
Dialysis Dose and OutcomeRonco et al. Lancet 2000; 351: 26-30
• Conclusions:– Minimum UF rates should be ~ 35 ml/kg/hr– Survivors had lower BUNs than non-
survivors prior to commencement of hemofiltration
425 patientsEndpoint = survival 15 days
after D/C HF
146 UF rate 20ml/kg/hrsurvival significantly lower
in this group compared to the others
139 UF rate 35ml/kg/hrp=0.0007
140 UF rate 45ml/kg/hrp=0.0013
Assessment Worldwide Acute Kidney Epidemiology Neonates
AWAKEN
Published on September 7th, 2017 – Lancet: Child and Adolescents - online first
AKI Outcomes in AWAKEN study
No AKIAKI
Infants with either AKI had higher mortality rate compared to thoseWithout AKI
AKI: 59/605 (9.7%) vs. NO AKI: 20/1417 (1·4%) p<0·0001
Prophylaxis of Neonatal AKI Theophylline may protect asphyxiated
infants against AKI: However:
Insufficient information on long-term renal or neurodevelopmental outcome
Different doses between trials Toxicity remains unclear Unsure of interaction/benefit with hypothermia
Al-Wassia et al. J Perinatol 2013
Uric Acid Uric Acid is elevated in
Dehydration AKI and CKD Tumor Lysis Syndrome
Treatment of elevated uric acid may improve renal function in AKI
Lessons from the Tumor lysis literature Allopurinol vs Rasburicase
Coiffier, B. et al. J Clin Oncol; 21:4402-4406 2003
Fig 3. Mean uric acid and creatinine levels ({+/-} standard error of the mean) evolution during rasburicase treatment
Methods 7 infants
34 + 55 days (range 3-155 days) 3.2 + 1.2 kg (range 2.7-5.7 kg)
AKI due to HIE 3/7, sepsis with AKI 3/7, ATN 1/7
Initial evaluation demonstrated normal urinalysis and renal ultrasound. Prior to use of Rasburicase no infant had responded to volume, diuretics nor vasopressor agents.
Base line Data(avg + SD)
Parameter (nl) Day 0 Cr mg/dl (0.3) 3.2 + 2BUN mg/dl (10) 58 + 57Phos mg/dl (6) 6 + 1.5K mmol/l (3-5) 4.1 + 0.8Ca mg/dl (8-9) 8.6 + 1.6Uric Acid mg/dl (< 6) 13.6 + 4.5Urine out put mls/kg/hr 2.4 + 1.2Syst/Dias-average 81/44
Initial data Urine out put /24 hrs
All pts had fluid overload despite urine output of 2.4 mls/kg/hr with no benefit from vaso-pressor agents nor diuretics
Due to elevation of uric acid a single dose of Rasburicase (0.17 mg/kg/dose) was administered IV
Data before and after Rasburicase(avg + SD; * p < 0.05)
Parameter (nl) Day 0 Day 1Cr mg/dl (0.3) 3.2 + 2 2.0 + 1.2 *BUN mg/dl (10) 58 + 57 31 + 18Phos mg/dl (6) 6 + 1.5 6.4 + 1.5K mmol/l (3-5) 4.1 + 0.8 3.6 + 0.8Ca mg/dl (8-9) 8.6 + 1.6 8.5 + 1.4Uric Acid mg/dl (< 6) 13.6 + 4.5 0.9 + 0.6 *Urine out put mls/kg/hr 2.4 + 1.2 5.9 + 1.8 *Syst/Dias-average 81/44 83/48
Long Term Follow up 2/7 infants died of sepsis No infants required RRT The remaining 5/7 infants were discharged
and have varying degree of CKD Hobbs et al , Pediatr Nephrol. 2010
Feb;25(2):305-9 CONTRAINDICATED IF G6PD IS PRESENT!
Mode of Dialysis PD (standard and continuous flow) HD (standard and High Flux) CRRT
CVVH CHHD CVVHDF
SLED
PD-standard Access-acute (non cuffed) or Cuffed Equipment-manual or automated Solutions-lactate or bicarbonate based from
Industry Heater-online Anticoagulation-intraperitoneal with no
systemic effect
PD-Access
Cuffed PD Access Acute PD Access Cook Critical Care acute PD
access Chest Tubes Feeding Tubes Angiocaths
PD-continuous flow
Access-two separate access Equipment-manual or
automated Solutions-Lactate of
Bicarbonate based solutions Heater-online Anticoagulation-
intraperitoneal with no systemic effect
Nourse, P; Pediatr Neph 2016, 3:1137-43
PATIENT SIZE CATHETER SIZE &
SOURCE
SITE OF INSERTION
NEONATE Dual-Lumen 7.0 French
(COOK/MEDCOMP)
Femoral vein
3-6 KG Dual-Lumen 7.0 French
(COOK/MEDCOMP)
Internal/External-Jugular,
Subclavian or Femoral vein
6-30 KG Dual-Lumen 8.0 French
(KENDALL/ARROW)
Internal/External-Jugular,
Subclavian or Femoral vein
>15-KG Dual-Lumen 9.0 French
(MEDCOMP)
Internal/External-Jugular,
Subclavian or Femoral vein
>30 KG Dual-Lumen 10.0 French
(KENDALL, ARROW)
Internal/External-Jugular,
Subclavian or Femoral vein
>30 KG Triple-Lumen 12 French
(KENDALL/ ARROW)
Internal/External-Jugular,
Subclavian or Femoral vein
www.pcrrt.com
6.5 and 5 Fr dual lumen not available in US
HD-Std or High Flux Access-as above Equipment-multiple machines Solutions-online production Heater-online Anticoagulation-heparin or none
Hemo Dialysis Machine Evolution
Drake-Willock: 1960s
Travenol RSP: 1960s Seratron: 1979
Cobe Centry: 1980sCobe C3: 1990s-2000s
Fresenius 2008h: 2000s
CRRT Access-as above Equipment-multiple machines Solutions-industry produced bicarbonate
based with or without calcium Heater-online Anticoagulation-heparin, citrate, prostacyclin
(www.pcrrt.com)
Machines and circuit volumes Primsaflex
93-150 mls with AN69 membrane (M series) B Braun Diapact
100-180 mls all with Polysulphone NxStage
83-183 mls all with Polysulphone Nikkiso
90-150 mls all with Polysulphone
Prismaflex Device with HF 20 Set60 mls volume
Blood flow(ml/min) 10-100 Dialysate flow (ml/h) 50-2500 Subst-flow rate (ml/h) 20-1000 Subst.prebp (ml/h) 30-1000 Volume reduction(ml/h) 10-2000 Heparin-Infusion (ml/h) 0.5-5.0
•Treatment options•SCUF•CVVH•CVVHD•CVVHDF•CVVHDF pre+postdil
Not available in the USWell published in Singapore, Austria
SLED Access-Same as CRRT and HD Equipment-Fresenius system
Same lines as use in HD Same membrane as used in HD Can be diffusive and or convective
Solutions-On line production Heater-on line Anticoagulation-heparin or citrate
Blood Priming is not without risk! May be needed in HD, CRRT and SLED Regardless of risk of membrane reaction the
large extracorporeal blood volume in these circuits compared to the infants may result in complications for blood bank blood has: pH of 6.5 Ica of 0.02 mmol/l (nl 1.1-1.3 mmol/l) K load up to 40 meq/300 mls of blood
Dialysis Dose
0123456789
10W
eekl
y st
dKt/
V
0.3 0.5 0.7 0.9 1.1 1.3 1.5eKt/V each dialysis
234567
No. of D
ays/week
EDD
35ml/kg45ml/kg
20ml/kg
Adapted from Gotch et al. Kidney Int 2000;58:S3-18
CRRT
PD
Pediatric Data-PD Recommendations of use of PD in situations
Cullis et al, PD for AKI, Peritoneal Dialysis International, 2013, 34:494-517
Recommendations of use of PD in situations of limited resources Vasudevan et al Modality of choice for RRT for
children with AKI Indian J Nephrol 2012 22121-124
Pediatric Data-CRRT Optimal use in situations of
Hemodynamic compromise Hyper metabolic states sepsis
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
Pediatric Data-SLED Using Fresenius System with Dialysis or
Dialysis with Convection (filtration) 14 children with 16 sessions ~ 8 hrs Heparin anticoagulation UF and Solute clearance achieved in 80% Cost compared to CRRT (SLED 69 $ vs CVVH
235$) Chia-Ying Lee et al, Peds Neph 2012 27:2301-2309
Pediatric Data-HD Best used in situations of
Hemodynamic stability Intoxication
Management of toxic ingestions with the use of renal replacement Pediatr Nephrol (2011) 26:535–541
In born error of metabolism in concert with CRRT Phenylacetate and benzoate clearance in a
hyperammonemic infant on sequential hemodialysis and hemofiltration. Pediatr Nephrol 2007; 22:1062-5.
Ammonia Clearance
0200400600800
10001200140016001800
1 2 3 5 7 11 15 17 19
HD Begins
Time(hours)
Am
mon
ia(m
icro
mol
/l) HD Ends HF BeginsHFEnds
RRT Modalities Modality CRRT SLED HD (standard
or HF) PD Continuous
Flow PDBFR 3-5 mls/kg/min
access dependent
3-5 mls/kg/min access dependent
3-5 mls/kg/min access dependent
10-20 mls/kg/pass
10-20 mls/kg/hr
Dialysis Flow Rate 0-4 liters/hr 6 liters /hr 30-50 liters/hr 0.5-2 liters/hr 0.5-2 liters/hr
Convective Flow Rate 0-4 liters/hr 0 0 0 0
Systemic Anticoagulation
Heparin or citrate
Heparin or citrate
Heparin or none none none
Thermic control Yes yes yes partial partial
Ultrafiltration control Yes yes yes partial partial
Solutions Industry made On Line production
On Line production
Industry made Industry made
Drug clearance Continuous Intermittent Intermittent Continuous ContinuousNutritional clearance Continuous Intermittent Intermittent Continuous Continuous
Long term followup Data shows ~ 25% of children with AKI
recovery at 5 years will have evidence of Increase in BP Evidence of microalbuminuria Evidence of hyperfiltration
Conclusion The optimal management of AKI is based
upon local experience and expertise Data to date does not exist nor will exist in
the future of an optimal RRT mode in most AKI situations
Do what you do well and it will work!
Thank you [email protected] [email protected] www.pcrrt.com
Contains all talks given at the PCRRT meetings from 2000 to the most recent in 2017 in Orlando
What is the earliest marker of AKI Change in serum creatinine Change in weight Change in the urine out put Urinary NGAL
What is the indication for RRT? Elevated potassium Elevated blood pressure due to fluid excess Pulmonary edema with oliguria not
responsive to diuretics All of the above