Bunchman Management of AKI - cairopedneph.com

Management of AKITimothy E. Bunchman Professor and Director

Pediatric Nephrology & TransplantationChildren’s Hospital of Richmond

Virginia Commonwealth Univ. School of [email protected]

[email protected]

Disclosure Safety committee for new device for Baxter

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

How do we define AKI?

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)

RIFLE Criteria

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

Fluid Overload as a Risk Factor

Foland et al, CCM 2004; 32:1771-1776

N=113*p=0.02; **p=0.01

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


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



26.9% of all patients



AWARE Investigators– submitted

Assessment Worldwide Acute Kidney Epidemiology Neonates

AWAKEN

Published on September 7th, 2017 – Lancet: Child and Adolescents - online first

AKI Incidence in AWAKEN study

No AKIAKI

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

Support of AKI Non dialytic Dialytic

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-Equipment

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)



>15-KG Dual-Lumen 9.0 French

(MEDCOMP)



>30 KG Dual-Lumen 10.0 French

(KENDALL, ARROW)



>30 KG Triple-Lumen 12 French

(KENDALL/ ARROW)



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)

CRRT Machines:Modern Generation

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

CARPEDIEM 27 mls

NIDUS 14 mls

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

Which modality is the best?

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

If a child has AKI and recovers then the child is without long term risk of CKD

yes no

Bunchman Management of AKI - cairopedneph.com

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