Timothy E. Bunchman - International Pediatric Nephrology ... Management_Timothy Bunchman.pdf ·...

Management of AKI

Timothy E. Bunchman

Professor and Director

Pediatric Nephrology & Transplantation

Children’s Hospital of Richmond

Virginia Commonwealth Univ. School of Medicine

[email protected]

[email protected]

www.pcrrt.com

http://www.pcrrt.com/

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 Combined

Setting DevelopingCountry/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)

EtiologyNumber (%, 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 4

Burkitt lymphoma 2

HIV related 3 (1.4)

Congenital malformation 10 (4.7)

Posterior urethral valves 6

Renal agenesis 4

Renal vein thrombosis 1 (0.5)

RIFLE Criteria

Pediatric Modified RIFLE Criteria

Estimated CrCl Urine output

Risk GFR decrease by 25% <0.5ml/kg/hour for 8 hours

Injury GFR decrease by 50% <0.5ml/kg/hour for 16 hours

Failure GFR decrease by 75% or GFR<35ml/min/1.73m2

<0.3 ml/kg/hour for 24 hours or anuric for 12 hours

Loss Persistent ARF > 4 weeks

End stage

End Stage Renal Disease (>3 months)

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 often excluded → loss of additional 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

1

SCr rise ≥ 0.3 mg/dl within 48 hrs or

SCr 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

3

SCr rise ≥ 3 X reference SCr * or

SCr ≥ 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 AKI

Period Acute Myocardial

Infarction

Acute Kidney

Injury

1960s LDH

1970s CPK, myoglobin

1980s CK-MB

1990s Troponin T

2000s Troponin IMultiple Therapies

50% ↓ Mortality

Period Acute Myocardial

Infarction

Acute Kidney

Injury

1960s LDH Serum creatinine

1970s CPK, myoglobin Serum creatinine

1980s CK-MB Serum creatinine

1990s Troponin T Serum creatinine

2000s Troponin I Serum creatinineMultiple Therapies

50% ↓ Mortality

Supportive Care

High 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

140 UF rate 45ml/kg/hrp=0.0013

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 AKI

AKI

AKI Outcomes in AWAKEN study

No AKI

AKI

Infants with either AKI had higher

mortality rate compared to those

Without 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 + 2

BUN mg/dl (10) 58 + 57

Phos mg/dl (6) 6 + 1.5

K mmol/l (3-5) 4.1 + 0.8

Ca mg/dl (8-9) 8.6 + 1.6

Uric Acid mg/dl (< 6) 13.6 + 4.5

Urine out put mls/kg/hr 2.4 + 1.2

Syst/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 1

Cr mg/dl (0.3) 3.2 + 2 2.0 + 1.2 *

BUN mg/dl (10) 58 + 57 31 + 18

Phos mg/dl (6) 6 + 1.5 6.4 + 1.5

K mmol/l (3-5) 4.1 + 0.8 3.6 + 0.8

Ca mg/dl (8-9) 8.6 + 1.6 8.5 + 1.4

Uric 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!

https://www.ncbi.nlm.nih.gov/pubmed/19936796

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


◼ Nikkiso


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

ee

kly

std

Kt/

V

0.3 0.5 0.7 0.9 1.1 1.3 1.5eKt/V each dialysis

234567

No

. of D

ays/w

ee

k

EDD

35ml/kg

45ml/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

0

200

400

600

800

1000

1200

1400

1600

1800

1 2 3 5 7 11 15 17 19

HD Begins

Time

(hours)

Am

mon

ia(m

icro

mol/

l)

HD Ends HF Begins

HF

Ends

RRT Modalities Modality CRRT SLED HD (standard

or HF) PD Continuous

Flow PD

BFR 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 Continuous

Nutritional 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

http://www.pcrrt.com/

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

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