Avoiding Kidney Injury

Pediatrics

Pediatric patient population: Postoperative AKI

• Majority of pediatric research focused on acute kidney injury after cardiac surgery &

liver transplant

• More pediatric research is required to examine intraoperative management of non-

cardiac surgical patients & impact on renal outcomes

• Disclaimer: Evidence provided in this presentation is based on literature from both

critical care and perioperative research.

Objectives

• Discuss incidence and impact of Acute Kidney Injury & Chronic Kidney Disease in pediatric

surgical patients

• Review the pathophysiology related to AKI and CKD in children

• Identify definitions & stages of kidney disease for infants and children

• Share registry definitions of kidney injury or failure - review ASPIRE AKI 01 measure

• Provide an overview of the literature studying the prevention and recognition of kidney

disease

• Summarize recommendations supported by the literature

For more information….

• For a more in-depth overview of kidney disease, including staging and definitions,

reference

• Avoiding Kidney Injury - Overview, Pathophysiology, Definitions

• For other specialty specific recommendations, reference the following sections of the

toolkit:

– Avoiding Kidney Injury – Obstetric Patients

– Avoiding Kidney Injury - Cardiac Surgery

– Avoiding Kidney Injury - Recommendations for Adult Surgical Patients

AKI Incidence in Pediatrics

• Largest epidemiologic study of AKI in children

using the Kids’ Inpatient Database (KID), an all

payer inpatient pediatric care database

– Included 2,644,263 admissions of

neonatal (≤ 1 month old) and children (

< 18 old) from over 4,000 hospitals in

the United States.

• Reported an AKI incidence of 3.9 cases per

1,000 admissions. AKI identified using ICD-9

codes.

• Incidence increased with age: 6.6 events per

1000 admissions in 15-18 year olds

• Mortality was 15.3% for children admitted

with AKI compared to non-AKI admissions

(0.6%)

Image Source: Sutherland et al. J Am Soc Nephrol. 2013

Pediatric AKI Multi-national Study

Assessment of Worldwide Acute Kidney

Injury, Renal Angina and Epidemiology

(AWARE) study

• Cohort of 4,683 critically ill children and

young adults (3 months to 25 years old)

admitted to pediatric intensive care

unit

– 30% were post-surgical patients

• 26.9% developed AKI; 3.4% died

Image Source: Kaddourah et al. N Engl J Med. 2017

Neonatal AKI Multi-national Study

Assessment of Worldwide Acute Kidney Injury, Renal

Angina and Epidemiology in Neonates (AWAKEN)

study

• 2,022 neonates admitted to NICU

• 29.9% developed AKI - rates varied by

gestational age

– 47.9% (22-29 weeks)

– 18.3% (29-36 weeks)

– 36.7% (> 36 weeks)

• Infants with AKI had a higher mortality

compared to those without AKI (9.7% vs. 1.4%)

• Highest prevalence in white males with GA < 36

weeks

Image Source: Jetton et al. Lancet Child Adolesc Health. 2017

Chronic Kidney Disease (CKD) Incidence

➔ ~ 10,000 children in the United States

have kidney failure

➔ 70% of children with CKD from diverse

etiologies will progress to ESRD before

reaching adulthood

➔ The ESRD incidence in African American

children is twice as that in caucasian

children

➔ 30-50% of children and adults with

congenital heart disease have CKD

End Stage Renal Disease (ESRD)

• Leading causes of ESRD in children

–

0 - 4 year olds



Birth defects and

hereditary diseases

–

5 - 14y



Hereditary diseases, nephrotic

syndrome and systemic diseases

–

15 - 19y



Diseases of the glomeruli

• One-Year mortality rate for pediatric patients

with ESRD has decreased by 20.4% over the

last decade with the most notable

improvement in those 0-4 years of age

Reported ESRD in Children/Adolescents (U.S.)

AKI Outcomes

Image Source: Sutherland et al. Clin J Am Soc Nephrol, 2015

• Mortality increases from 5% to 18% in neonates who develop

AKI after non-cardiac surgery

• A prospective national cohort study of 1,343 events of AKI in

patients less than 18 years old showed neonatal and pediatric

30 day mortality rates of 4.1%. and 1.2% respectively

• In a retrospective cohort study of 2,041 non-cardiac surgical

patients (<18 years old) admitted to the PICU, AKI was

independently associated with an increase from 5 to 7 year

mortality

• Severe AKI is associated with an increased risk of death (11%

vs. 2.5% w/o severe AKI). RRT is the second strongest

predictor of death by day 28 after admission

• Length of ICU stay increases in children with AKI from 4 to 10

days

Mortality and Modality – CKD

• The probability of surviving after RRT by

age is the lowest for children 0-4 years

old (0.83) and young adults 18-21 years

old (0.89)

– Patients who received a kidney transplant have

a higher probability of surviving 5 years when

compared to those treated with hemodialysis

or peritoneal dialysis

• In a study of 1,634 children and

adolescents requiring RRT, the long-term

survival rate was 79% at 10 years and

66% at 20 years.

• There are a limited number of studies on

the risk of CKD in children who

experience AKI.

Image Source: USRDS, 2019

Financial Impact of Kidney Disease

• Healthcare expenditures are 7.6x higher for children with CKD and increased by

50% over the last 10 years compared to a 25% increase in spending for children

without CKD

• The cost of dialysis for a neonate or infant compared to an adult patient with end

stage renal disease is $75,000 to $43,000 respectively

Acute Kidney Injury

Classification Systems

Acute Kidney Injury: General Definition

16-17

• Several AKI Classification Systems exist:

– RIFLE - Risk, Injury, Failure, Loss, End Stage - 2004

– AKIN - Acute Kidney Injury Network – 2007

– pRIFLE/nRIFLE – Pediatric and neonatal specific RIFLE

criteria– 2008

– KDIGO - Kidney Disease Improving Global Outcomes-

2012

Acute Kidney Injury

An abrupt decline in kidney function occurring

over a period of 7 days or less, characterized by:

● Reversible increase in serum blood creatinine

and nitrogenous waste products

● Inability of the kidney to appropriately

regulate fluid and electrolyte homeostasis.

AKI Classification Systems: RIFLE

• First attempt at a unifying definition for AKI (then called acute renal failure)

• Published in 2004, RIFLE graded AKI Stages and provided taxonomies for both severity and recovery

• Proposed 1 week timeframe for AKI Diagnosis

• Published in 2008, modifications for pediatrics (pRIFLE) and neonates (nRIFLE) include wider duration

of decreased urine output.

Image Source: Ricci et al. Kidney Int. 2008

AKI Classification Systems: KDIGO Criteria

GFR Criteria Urine output criteria

Increased creatinine

x1.5-1.9 from baseline or

≥ 0.3 mg/dl

UO <0.5ml/kg/hr for

6-12hr

Increased creatinine

x2.0-2.9 from baseline

UO <0.5ml/kg/hr ≥

12h

Increased creatinine x3

from baseline OR SCr ≥

4.0mg/dl OR RRT

UO < 0.3 ml/kg/hr for

≥ 24h

or anuria ≥ 12h

Diagnostic criteria for AKI:

- SCr increase ≥0.3mg/dl within 48h OR

- SCr increase ≥1.5 times baseline, which

is known or presumed to have occured

within the last 7 days OR

- Urine volume < 0.5 ml/kg for 6h

Kept SCr increase of

≥ 0.3 mg/dl within 48

hours from AKIN

Used 7 day

timeframe for 1.5X

increase in SCr from

RIFLE

SCr criteria mostly

unchanged from

AKIN

Removed acute rise

criteria. Kept RRT

criteria from AKIN

UO criteria

unchanged

KDIGO has been validated as a clinically

relevant AKI classification system in the

pediatric population. There have been calls

to utilize the KDIGO AKI definition as the

standard for defining AKI in pediatrics

AKI Classification Systems: KDIGO in neonates

• Serum creatinine is a suboptimal biomarker in the neonatal population due to presence of maternal creatinine, variable degree

of creatinine reabsorption, low glomerular filtration rate and maturational differences.

• Modification of KDIGO criteria for neonates (nKDIGO) stages AKI based on an absolute rise in serum creatinine from a previous

trough and should be used in children < 120 days of age.

• Severity of AKI based on neonatal KDIGO (nKDIGO) criteria was independently associated with ICU stay, renal replacement

therapy and increased in-hospital mortality within 30 days after cardiac surgery.

Image Source: Selewski et al. Pediatrics. 2015

Image Source: Sutherland et al. Clin J Am Soc Nephrol. 2015

pRIFLE vs. AKIN vs. KDIGO

• pRIFLE provides more sensitivity to identifying a

greater number of mild AKI cases children

– Demonstrated that doubling of SCr in children associated with

27.4% mortality rate

– 75% of pediatric patients are admitted without a baseline SCr

lab value

– Using 120 mL/min/1.73m

in place of an actual baseline can

lead to underdiagnosis of AKI using pRIFLE criteria

• AKIN does not require height or baseline creatinine

values - may be advantageous as baseline SCr values

are rarely available in pediatrics

• KDIGO is applicable to both pediatric and adult

patients and has a less restrictive diagnostic timeframe

than AKIN. Both pRIFLE and KDIGO determine stages of

AKI by changes in serum creatinine (SCr)/estimated

creatinine (eCCl) clearance and changes in urine

output.

Image Source: Sutherland et al. Clin J Am Soc Nephrol. 2015

Estimated Glomerular Filtration Rate (eGFR)

• Calculating an eGFR is necessary for accurate staging of

CKD in children. Renal development and function is still

maturing in children less than two years old

• Baseline SCr is often not available in pediatric patients making it

difficult to estimate baseline kidney function.

• Chronic Kidney Disease in Children (CKiD) study derived a

Schwartz formula for patients 1-16 years of age

eGFR (ml/min/1.73m

) = [height in cm x 0.413] / SCr in mg/dL

Image Source: Sutherland et al. J Am Soc Nephrol. 2015

AKI

Pathophysiology

and Etiology

Image Source: Gumbert et al. Anesthesiology. 2020

Pathophysiology: Anesthetic Impact on AKI

27-28

• Hypovolemia and venodilation

• Positive pressure ventilation can impair venous return to the heart

• Anesthetics can reduce arterial tone which decreases perfusion pressure.

• Right sided hemodynamics are critical, as high venous pressure can cause kidney injury

through organ congestion.

– Cardiac surgery: right side of the heart may be compromised from cardioplegia.

– Thoracic surgery: increased pleural pressure may increase venous “back pressure” on the liver and

kidneys

– Abdominal surgery: High insufflation pressure in the abdomen

• Ischemia-reperfusion causes damage associated molecular pattern (DAMP) molecules

to be released into circulation such as myoglobin and uric acid.

Etiology: Pre-renal

Renal Hypoperfusion due to true

volume contraction: Hemorrhage,

dehydration, increased insensible losses (burns)

and other third space losses such as sepsis,

nephrotic syndrome, traumatized tissue and

capillary leak syndrome

Decreased effective intravascular

volume:

Renal perfusion decreased due to low

cardiac output states, such as from congenital

heart defects

Etiology: Renal (Intrinsic)

• Results of injury to kidney structures: tubules,

glomeruli, the interstitium, and intra-renal blood

vessels

• Acute Tubulointerstitial nephritis

• 3 Main Causes in Children

– Acute Glomerulonephritis (stage 1)

– Septicemia (stage 3)

– Antibiotic drug-induced AKI (stage 3)

Etiology: Intrinsic Possible Causes

16,29

Tubular:

● Renal ischemia (shock,

complication of surgery,

hemorrhage, trauma,

bacteremia),

● Nephrotoxic drugs

● Endogenous toxins such as uric

acid excretion caused by tumor

lysis syndrome in children with

Leukemia

Glomerular:

● Acute post infectious

glomerulonephritis

● Lupus nephritis

Interstitium:

● Infectious (bacterial, viral)

● Medications (antibiotics,

diuretics, NSAIDs)

● Acute Interstitial Nephritis

(idiopathic or drug induced)

Vascular:

● Cortical necrosis is common

in young children,

particularly neonates

● Associated with ischemic

insults due to perinatal

anoxia, placenta abruption

and twin-twin or twin-

mother transfusions

● Hemolytic uremic syndrome

Etiology: Postrenal

• Caused by blockage of urinary flow in the urinary tract

• Obstruction → ↑ intratubular pressure and ↓GFR

– Leads to build up in the kidney

• Quick resolution = best chance of kidney recovery

Etiology: Post Renal Possible Causes

16,29

Extrarenal Obstruction:

congenital malformations such as

posterior urethral valves, bilateral

ureteropelvic junction

obstruction or bilateral

obstructive ureteroceles

Intrarenal Obstruction:

Nephrolithiasis, blood clots

AKI Risk Factors

Anesthesia-related Risk Factors

Potentially modifiable AKI risk factors in both pediatric cardiac and noncardiac surgery

33-35

– Hemodilution

– Hemoglobin level

– Intraoperative transfusion

– Hypotension

– Inadequate oxygen delivery

– Use of diuretics

– Use of vasopressors and inotropes

– Selective renal ischemia

– Ischemia reperfusion injury

– Bleeding complications

– Transfusion of allogeneic blood products

– Intraoperative Hypertension

– Nephrotoxic agents (eg abx, contrast agents)

Image Source: Think Kidneys 2019

AKI Risk Factors: Neonatal

• Maternal

– NSAID use

• Perinatal

– Gestational age under 32 weeks

– Congenital heart defect

• Postnatal

– Low Apgar score (< 7)

– Low birth weight (< 1500g)

– Mechanical Ventilation

– Surgical procedure longer than 120 min

– Diagnosis of necrotizing enterocolitis

– Resuscitation with epinephrine

– Admission diagnosis of hyperbilirubinemia

AKI Risk Factors: Pediatric

• Nephrotoxic Drugs

– Administration of IV vancomycin with or without IV administration

piperacillin/tazobactam

36-38

– Aminoglycosides

39-42

• Comorbidities

39-40, 43-45, 46

– Cystic fibrosis

– Liver transplant recipients

– Vaso-occlusive crisis

– Diabetic ketoacidosis

– Oncologic diagnosis

• Age and sex - no consistent correlations

• Other associated factors

– Sepsis

– Heart failure

– Tumor lysis syndrome

AKI Risk Factors: Cardiac Surgery

• Independent risk factors for AKI identified in children undergoing cardiac surgery

– Young age (< 1 year)

– Risk adjustment in Congenital Heart Surgery category (RACHS-1) ≥ 4

– Cardiopulmonary Bypass time ≥ 90 minutes

• Children with congenital heart disease have an increased risk of postoperative AKI

– 86% Incidence using KDIGO  Dependent on age, heart disease, cardiac status, CPB technique,

management of anesthesia and postoperative care practices.

– Other risk factors specific to children with congenital heart disease include previous cardiac surgery,

univentricular anatomy, inotrope and captopril use or PICU admission preoperatively with or without

mechanical ventilation

• Wide fluctuations in blood glucose intraoperatively increases the risk of AKI (using

AKIN criteria).

– Acute hyperglycemia insults alone does not increase the risk of AKI in this population

Registry Definitions:

Kidney Disease

National Surgical Quality Improvement Program - Pediatrics

Progressive Renal Insufficiency:

- Rise in creatinine of >1 mg/dl from preoperative value, but with no requirement for

dialysis within 30 days of the operation.

Acute Renal Failure:

- In a patient who did not require dialysis preoperatively, worsening of renal dysfunction

postoperatively requiring hemodialysis, peritoneal dialysis, or ultrafiltration within 30

days of the operation.

Days from Operation until Acute Renal Failure Complication

Source: ACS-NSQIP-Pediatrics User Guide

STS - Congenital Heart Data Registry

Renal Failure requiring Dialysis

- Oliguria with sustained urine output < 0.5 cc/kg/hr for 24 hours and/or a rise in

creatinine >1.5x upper limits of normal for age (or 2x the most recent preop values if

available), with

need for dialysis (including peritoneal dialysis and /or hemodialysis) or

hemofiltration

- Requiring dialysis before hospital discharge (even if greater than 30 days after surgery)

- Requiring dialysis after hospital discharge but within 30 days after surgery

Source: STS Congenital Heart Surgery Database Data Specification

Children’s Hospital Solutions for Patient Safety

• Nephrotoxic medication exposure is one of the most

common causes of AKI in children

• Defined as a Class 4 (significant temporary harm) Serious

Safety Event by the Children’s Hospitals’ Solutions for Patient

Safety

• SPS has partnered with the NINJA program with plans to

rollout to all 140 sites by 2020

42,50

– NINJA - Nephrotoxic Injury Negated by Just-in-time Action

– Uses KDIGO Diagnostic criteria

– Proactively screens for nephrotoxic drug (NTMx) exposure in EHR

– High risk patients are monitored via daily SCr lab orders

Source: Solutions for Patient Safety

ASPIRE Measure Definition: AKI 01

Pediatric Patients ≤ 18 years old

• KDIGO Criterion used

• EGFR Calculation

– Bedside Schwartz

EGFR = 0.413 x [(height in cm)/(serum creatinine in mg/dL)]

• Exclusion criteria: baseline creatinine <0.2mg/dL

– Baseline serum creatinine is defined as the most recent serum

creatinine resulted in the last 60 days preoperatively

• Success criteria:

– The creatinine level does not go above 1.5x the baseline creatinine

within 7 days post-op

– The creatinine level does not increase by ≥ 0.3 mg/dL obtained

within 48 hours after anesthesia end.

Source: ASPIRE Measures-Acute Kidney Injury

AKI Pediatric

Recommendations

Pediatric and Neonate Recommendations

Treatment Considerations

● Correct electrolytes

● Avoid fluid overload

● Consider Renal Replacement Therapy

● Identify precipitating factors of AKI

● Early recognition prevents further progression

● Renal Angina Index

Early recognition of AKI

Prevention of AKI

● Avoid nephrotoxins

● Maintain Fluid Balance

● Normalize preoperative nutrition status

Identify patients at risk of

developing AKI

● Anesthesia related risk factors

● Pediatric risk factors (neonates & children )

● Risk factors specific to cardiac surgery

Recommendation #1:

Identify patients at risk

for AKI

*See slides 28-32 for pediatric risk factors

Recommendation #2:

Prevention of AKI

Image Source: Basu et al. Clin J Am Soc Nephrol, 2018

Nephrotoxic Medication (NTMx) Exposure Defined

Nephrotoxic Medication exposure criteria

• ≥ 3 NTMx meds

• ≥ 3 days on any IV aminoglycosides

• ≥ 3 days on Vancomycin

AKI Criteria for NTMX exposed patients

• At least 50% increase in SCr above baseline SCr (lowest SCr in the past 6 months), with the increased

value above a threshold of 0.5 mg/dL

• An absolute increase of 0.3 mg/dL in SCr within 48 hours, regardless of the maximum value (minimum

threshold value must be 0.5 mg/dL for peak creatinine)

For NTMx-AKI events in NICU:

• Screening begins on day of life 4 (after 72 hours of life)

• Baseline determined by the lowest creatinine on record

• Rationale: up until day ~4, creatinine is reflective of maternal creatinine and is unlikely to be at nadir

Nephrotoxic Medications for Monitoring

Image Source: Children’s Hospitals’ Solutions for Patient Safety

Avoid Nephrotoxic Medications

The Nephrotoxic Injury Negated by Just-in-time Action Program (NINJA)

52-53

• Proactively screens for nephrotoxic drug (NTMx) exposure in EHR and flags patients at high risk for

NTMx-AKI

• High risk patients are monitored via daily SCr lab orders

• Single-center implementation reduced exposure of nephrotoxic drugs in children by 38% and AKI rate

was reduced by 64%

• Multi-center preliminary data based on a 3 year implementation of NINJA is showing a 23.8%

reduction in AKI rates across all nine centers.

Maintain Fluid Balance

Avoid over transfusion during surgery

• A single-center retrospective study (n=220) patients ages 10 days - 19 years who underwent cardiac

surgery in 2012

• 41.8% developed AKI (KDIGO) and 8.2% required RRT within the first week after surgery. Majority of

patients were AKI stage 1 (25.9%)

Hypovolemia

• “The hypoperfusion due to decreased microvascular flow may contribute to the renal ischemic damage

especially during cardiac surgery where low cardiac output and cardiogenic shock may frequently occur”

• Treatment: infuse 10-20 ml/kg of normal saline

– If urine output does not increase, consider CVP monitoring

AKI Incidence: Correlation between transfusion volume, hemoglobin level, and

AKI

Image Source: Park et al. PLoS One. 2016

Optimize Nutrition Status Preoperatively

In retrospective analysis of 95 neonates who had congenital heart surgery:

– 66 patients (69.5%) did not achieve preoperative caloric goal

– 29 patients (30.5%) did reach caloric goal

– Higher incidence of stage 2 or 3 AKI postoperatively for those who did not reach

caloric goal as compared to those who did (P=0.04; odds ratio, 4.48; 95% confidence

interval, 1.02-19.63)

Recommendation #3:

Early Recognition of AKI

- Identification of patients at risk facilitates early intervention with bundle implementation

which has been shown to protect the kidneys and reduce mortality

56-58

- American Society of Nephrology launched AKI!NOW initiative to promote early

recognition and management of AKI which helps optimize treatment and prevent

progression.

AKI!NOW Recommendations:

- Provider education at all levels in healthcare regarding AKI, particularly around identifying

patients at risk

- Generate specific guidance on AKI evaluation and management

- Develop global toolkit

- Engage hospital administration and make AKI a part of quality initiative

- Raise awareness of AKI as complication of other disease processes

Emerging Research - Biomarkers

The use of NGAL and Cystatin C to detect AKI in pediatrics after cardiac surgery has been

reported as feasible.

4,60

- NGAL - tubular biomarker

- Most studied in pediatrics, especially cardiac surgery population

- Can detect changes as early as 2 hours after CPB

- Associated with AKI severity, length of mechanical ventilation, and length of ICU stay

11, 61-62

- Superior to creatinine for detection of aKI

11,64-66

- Cystatin C - functional biomarker

- Protease inhibitor that is released by nucleated cells at a constant rate → filtered by the glomeruli → reabsorbed in

the renal tubules.

- Reflects a decrease in GFR if found in urine.

- Superior biomarker to serum creatinine in the assessment of GFR in premature infants

- Serum phosphorus - alternative biomarker that can be used for early prediction of AKI in pediatric cardiac surgery as early

as 24 hours postoperatively

Emerging AKI Biomarker Research

Image Source: Ciccia & Devarajan. Int J Nephrol Renovasc Dis. 2017

Renal Angina Index: Proactive Recognition of AKI

2,69

• Highly sensitive screening tool for AKI that

combines risk factors and early signs of

decreased kidney function (increased SCr or

degrees of fluid overload) to stratify patients for

risk of subsequent severe AKI.

• Predictive efficacy of the RAI for development of

severe AKI three days after admission to the ICU

was tested in a multinational, multi-center

prospective study of 5,237 children

– AKI Incidence was significantly higher in

the group assessed to have renal angina

(RAI score of > 8).

• Assessment of AKI according to SCr levels alone

failed to identify AKI in 67.2% of patients with

low urine output

Image Source: Ciccia & Devarajan. Int J Nephrol Renovasc Dis. 2017

Recommendation #4:

Treatment Considerations

Manage Acidosis & Electrolyte Imbalances

• Kidneys excrete net acids generated by diet & metabolism

• Acidosis is common in AKI and CKD

– Treat with IV or oral sodium bicarbonate

• Consider serum total and ionized calcium levels before treating acidosis

– Hypocalcemia is common in AKI & treatment of acidosis can cause tetany or seizures due to drop in

ionized calcium

• Hyperphosphatemia is also common

– Limit dietary phosphorus

– Treat with oral calcium carbonate (to bind with phosphorus & prevention further absorption)

– Must take into consideration acid-base balance

Hyperkalemia: Potentially life-threatening

• Kidneys regulate potassium balance

– 90% of dietary potassium intake is excreted through kidneys

• Hyperkalemia common in AKI and CKD due to:

– Decreased filtration and tubular secretion

– Altered distribution of potassium by acidosis → shifts potassium from intracellular to extracellular compartment

• If potassium reaches levels > 6-7 mEq/L or cardiac conduction abnormalities occur, consider

treatment:

Image Source: Andreoli. Pediatric Drugs. 2008

Assess for Hyponatremia

• Hyponatremia is common in AKI as kidneys fail to

excrete excess fluid leading to dilutional hyponatremia

• Treatment requires fluid restriction or water removal by

dialysis or hemofiltration; slow infusion of hypertonic

saline solution may be necessary

• If serum sodium level < 120mEq/L due to excess water

retention, seizures may result

Image Source: Andreoli. Pediatric Drugs. 2008

Renal Replacement Therapy in Children

Factors to consider:

• Age

• Size of child

• Cause of Renal Failure

• Degree of metabolic

derangements

• Blood Pressure

• Nutritional Needs

• Peritoneal dialysis vs. intermittent

hemodialysis vs. hemofiltration

The most common initial ESRD treatment modality among children is hemodialysis (56

percent)

Image Source: Andreoli. Pediatric Drugs. 2008

Peritoneal and Hemodialysis in Neonates

• Unique challenges with managing AKI in neonates due to developing nephrons,

small blood vessels (difficult hemo catheter access) and peritoneal space.

– Limited evidence that renal replacement therapy (RRT) in patients ≤ 1yo

is effective or improves long term outcomes especially patients with:

– History of abdominal surgeries

– Surgical site infections

– Require fluid removal faster than the peritoneal membrane allows

• Peritoneal dialysis (PD) is used more often in children than in adults however,

children with CKD are given hemodialysis (HD) more frequently than PD or

kidney transplant.

• Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)

– Five year prospective study designed to develop and implement this machine which has an

extracorporeal priming volume of < 30mL and accurate ultrafiltration to within 1g.

– Used effectively in infants as small as 2.9 kg

Postoperative AKI

Cardiac, General and Liver

Pathophysiology of AKI related to Cardiopulmonary bypass

Nadim and colleagues depict the

many variables associated with

cardiac surgery & cardiopulmonary

bypass:

- Nonpulsatile blood flow

- Extensive Hemodilution

- Transfusion load

- Release of free hemoglobin

& free iron from hemolysis

- Prolonged hypothermia

- Inflammatory response

- Venous congestion

All of these factors can contribute

to acute kidney injury.

Image Source: Nadim et al. J Am Heart Assoc. 2018

Peds Cardiac Surgery - AKI

• AKIN definition modified for children 0-36 months old to

greater than 0.1 mg/dL increase in SCr was required to

assign cardiac surgery-associated acute kidney injury

(n=799)

– 36% of patients had AKI with the majority (76%) having

stage II or III AKI.

• A small rise (less than 50%) in SCr on postoperative day 1

predicted AKI within 48 hours after cardiac surgery using

pRIFLE criteria

• Mortality rate is higher in patients following recovery from

AKI, regardless of staging, compared to those without AKI

after cardiac surgery

Image Source: Hirano et al. Am J Nephrol. 2017

AKI after Pediatric General Surgery

Neonates undergoing non-cardiac

surgical procedures with general

anesthesia (n=160)

• Using nKIDGO, 33.8% of neonates

developed AKI

• Higher mortality rate than those

who did not develop AKI

AKI after Pediatric Liver Transplant

Liver Transplant AKI Risk Factors

73-75

– Hypoalbuminemia

– High requirement for RBC and 20% human albumin

transfusions

– Elevated preop labs: serum sodium, aPTT, bilirubin, end of

surgery lactate levels and BUN levels

– High furosemide use and high flow of ascites

– Need for open abdomen

Incidence of AKI after liver transplantation in pediatrics

• pRIFLE is 20% more sensitive than AKIN when determining the

severity of AKI (n=57)

• KDIGO staging has shown 35.8% of patients have AKI (n=117) and

15% of those children required RRT postoperatively.

• Another study has demonstrated 46.2% of patients develop AKI

using KDIGO (n=156)

– Assessment of AKI according to SCr levels alone failed

to identify AKI in 54.3% of patients with low urine

output

Summary

1. Anesthesia providers should focus on reducing the anesthesia-related intraoperative risk factors

associated with AKI such as:

• Avoid nephrotoxins

• Maintain Fluid Balance

• Ensure preoperative nutrition status

• Theophylline administration for neonates

2. Assessing risk factors preoperatively can assist anesthesia providers in identifying patients who

may require additional interventions to prevent AKI.

3. Early Recognition of AKI optimizes treatment and reduces risk of progression to later stages of

kidney disease.

References

1 Sutherland SM, Ji J, Sheikhi FH, et al. AKI in hospitalized children: epidemiology and clinical associations in a national cohort. Clin

J Am Soc Nephrol. 2013;8(10):1661-1669.

2 Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, AWARE Investigators. Epidemiology of Acute Kidney Injury in Critically Ill

Children and Young Adults. N Engl J Med. 2017;376(1):11-20.

3 Jetton JG, Boohaker LJ, Sethi SK, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre,

multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1(3):184-194.

4 Toda Y, Sugimoto K. AKI after pediatric cardiac surgery for congenital heart diseases–recent developments in diagnostic criteria

and early diagnosis by biomarkers-. J Intensive Care Med. 2017;5(1):49.

5 Kellum JA, Bellomo R, Ronco C. The Concept of Acute Kidney Injury and the RIFLE Criteria. In: Vol 156. ; 2007:10-16.

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