Acute Kidney Injury (AKI) Recognition and Management in ......312 studies, 152 using KDIGO-AKI, 50 million episodes Pooled AKI incidence 21.6% in adults, 33.7% in children Pooled AKI

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Acute Kidney Injury (AKI)Recognition and Management in General Pediatrics

Samhar Al-Akash, MD

Pediatric NephrologyDriscoll Children’s Hospital

Corpus Christi, TXUSA

26th Annual Pediatric Conference Driscoll Health System

Corpus Christi, TXJuly 26-27, 2019

Disclosures

• No financial conflicts to disclose

Objectives

� Definitions and classification of AKI� Significance / Epidemiology / Impact of AKI� Risk factors for AKI� Etiology and pathophysiology of AKI (nephrotoxic)� AKI and CKD� Biomarkers - Early recognition and diagnosis of AKI � Management guidelines and best practices

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AKI - Definition

� Abrupt loss of kidney function that results in:� Decline in GFR (serum creatinine) � Retention of urea and other nitrogenous wasted

products (BUN)� Dysregulation of extracellular volume and electrolytes

(volume, Potassium, acid-base)

� Formerly known as acute renal failure:� Did not reflect a continuum of manifestations� Late recognition

Definition of Acute Kidney InjuryRIFLE

R Bellomo et al, Critical Care 2004; 8: R204-R212Z Ricci et al, Kidney Int 2008; 73: 538-546

Definition of Acute Kidney InjurypRIFLE

Z Ricci et al, Kidney Int 2008; 73: 538-546

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Definition of Acute Kidney InjurypRIFLE

Z Ricci et al, Kidney Int 2008; 73: 538-546

� Example 1:� 5-year-old � SCr 0.4 on admission� SCr 0.6 on day 2 � CrCl is lower by 50%

� Injury (AKI)

� Example 2:� 2-year-old � SCr 0.5 on day 3 (from 0.3) � CrCl is lower by 67%� Injury (AKI)

� Urine output 0.2 ml/kg/hour – Failure

Definition of Acute Kidney InjuryAKIN

D Cruz et al, Critical Care 2009; 13: 211-220

Definition of Acute Kidney Injury

KDIGO, Kidney Int 2012; S2: 19-36

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Definition of Acute Kidney Injury

KDIGO, Kidney Int 2012; S2: 19-36

Worldwide Epidemiology of AKI

P Susantitaphong et al, Clin J Am Soc Nephrol 2013; 8: 1482-1493

312 studies, 152 using KDIGO-AKI, 50 million episodesPooled AKI incidence 21.6% in adults, 33.7% in children

Pooled AKI mortality rates 23.9% in adults, 13.8% in children

Worldwide Epidemiology of Acute Kidney Injury


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Worldwide Epidemiology of Acute Kidney Injury


Worldwide AKI - Mortality


Worldwide Epidemiology of AKI - KDIGO

E Hoste et al, Nature Rev Nephrol 2018; 14: 607-625

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Pediatric AKI and Survival (KDIGO) - AWARE

A Kaddourah et al, New Eng J Med 2017; 376:11-20

• AWARE

• N = 4683

• AKI 26.9%• Severe AKI 11%

OR 1.77

AKI Prevalence - ICU

A Kaddourah et al, New Eng J Med 2017; 376:11-20

Epidemiology of AKI - Children

S Sutherland et al, Clin J Am Soc Nephrol 2013: 8: 1661-1669

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• KID = Kids Inpatient Database.

• All payer, 4121 Hospitals, 44 states

• Analysis of 2009 data

AKI in Children – Mortality and Morbidity


AKI in Children – Mortality and Morbidity


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Mortality/Severe AKI – Who is at greatest risk?

S Sutherland et al, Clin J Am Soc Nephrol 2013: 8: 1661-1669R Basu et al, Lancet Child Adolesc Health 2018; 2(2): 112-120

� Sepsis� Shock� Vasoactive support� Mechanically ventilated� Lower UOP� Malnourished – underweight

� RENAL ANGINA INDEX (RAI) > 8Risk level Description Risk

score

Moderate ICU status 1

High Transplant 3

Very high Mech. vent./inootropes 5

Injury (SCr) Injury (fluid overload) Injury Score

No change < 5% 1

Stage 1 > 5% 2

Stage 2 > 10% 4

Stage 3 > 15% 8

X





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Pediatric AKI

S Sutherland et al, Clin J Am Soc Nephrol 2015; 10(4): 554-561

• Stanford Lucile-Packard

• 2006-2010

• Observational – EMR enabled

• AKI based only on SCr

Pediatric AKI – Incidence



Pediatric AKI – Mortality

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Pediatric AKI - Mortality


Acute Kidney Injury - Morbidity


Acute Kidney Injury - Neonates

J Jetton / D. Askenazi et al, lancet Child Adolesc Health 2018; 1(3): 184-194

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J Jetton / D. Askenazi et al, lancet Child Adolesc Health 2018; 1(3): 184-194


AKI in Non-critically Ill Children

N. Donmez, K. Hyunh, Z. Perez, S. Al-Akash – PAS Toronto May 2018

� Incidence 5%� Driscoll Children’s Hospital:

� Retrospective study 1/1/2016 – 1/1/2017� Using SCr criteria (0.3 increase or > 50% above baseline)� EMR-based inquiry� Exclusions: PICU prior to AKI, < 1 month, transplant, CKD� Results:

� AKI incidence 6.2% (114 of 1844 admissions)� Median eCrCl (Schwartz) 49 vs. 133 ml/min (P < 0.0001)� Only 24% had a diagnosis of AKI in the chart� With nephrology consult 62.5% documented AKI in the chart

(OR 9.9, p <0.0001)� 67% of patients with AKI had nephrotoxic exposure (1-28%, 2 or

more 39%) (NSAID’s 40%, Vancomycin 36%)� Nephrotoxic exposure increased hospital LOS 3 days on average

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Aminoglycoside-associated AKI in Children

1M Zappitelli et al, Nephrol Dial Transplant 2011; 26(1): 144-1502J Saban et al, Pediatr Nephrol 2017; 32(1): 173-179

� Aminoglycoside (AG) toxicity in 20% (AKIN) and 33% (pRIFLE) of children (Gentamicin 88%) 1

� Exposure (median duration of AG therapy) is associated with increased severity of AKI2:� Stage 1 – 98 hours� Stage 2 – 231 hours� Stage 3 – 111 hours

� Prior exposure to AG was associated with higher risk of AKI2:� 1.5 + 1.8 episodes (AKI) vs 0.9 + 1.6 (no-AKI)� Tobramycin, younger age, # of AG treatment days, Hem/Onc

Economic Impact of AKI

Acute Kidney Injury (AKI) &Chronic kidney Disease (CKD)

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AKI – Natural History

J Cerda et al, Clin J Am Soc Neprol 2008; 3: 881-886

AKI – Natural History

L Chawla et al, Kdiney Int 2011; 79: 1361-1369

CKD after AKI

S Mehta et al, BMC Nephrol 2018; 19: 91-101

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AKI Increases Risk for CKD

L Forni et al, Intensive Care Med 2017; 43: 855-866

AKI and Survival

O Rewa et al, Nature Rev Nephrol 2014; 10: 193-207


L Forni et al, Intensive Care Med 2017; 43: 855-866

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CKD After AKI in Developed Counties

S. Goldstein et al, Clin J Am Soc Nephrol 2013; 8(3): 476-483

CKD after AKI

C Mammen et al, Am J Kidney Dis 2012; 59(4): 523-530

� Critically-ill children:� Patients admitted to PICU 2006-2008 with AKI (n = 126)� Survivors assessed at 1, 2, 3 years� AKIN classification (stages: 1 = 35%, 2 = 37%, 3 = 28%)

� CKD: microalbuminuria and/or eGFR < 60 ml/min� Overall CKD 10%:

� stage 1-4.5%, 2-10.6%, 3-17.1%

� At risk for CKD: eGFR 60-90 ml/min, HTN, or eGFR > 150 ml/min� 46.8% overall

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CKD after AKI

S Hui-Stickle et al, Am J Kidney Dis 2015; 45(1): 96D Askenazi et al Kidney Int 2006; 69(1): 184

� Critically-ill children:� Patients admitted 1998-2001� 254 AKI episodes in 248 children� Cause of AKI: renal ischemia (21%), nephrotoxic (16%),

sepsis (11%), renal disease (17%)

� Overall survival 70%

� At discharge - 34% had CKD or were dialysis dependent � At 3-5 year FU:

� CKD in 60% (microalbuminuria, proteinuria, HTN, decreased GFR)

� ESRD in 9%

AKI – Children at Risk

� Critically-ill children:� Post-cardiac surgery

� Longer bypass times� Younger age and lower weight� Lower pre-operative creatinine� Mechanical ventilation

� Non-cardiac (others):� Younger and older ages� Mechanical ventilation� Higher PRISM score � Hypovolemia� Coagulopathy� Vasopressor support� Nephrotoxic medications

AKI – Children at Risk

� Non-critically-ill children:� Younger age� Lower birth weight� Lower baseline serum creatinine� Higher Exposure to nephrotoxic medications:

� Higher dose� More frequent dosing � Longer duration of therapy

� Higher number of nephrotoxic medications uses� Aminoglycoside associated AKI:

� Higher exposure� Prior aminoglycoside treatment (especially within prior 30days)� Hem/Onc service� Hypoalbuminemia / hypovolemia� Other nephrotoxic exposure� Neonate

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AKI - Etiology

P Stephens, Medicine 2007; 35(8): 429-433

Nephrotoxic AKI - Etiology

� Drug-related factors� Patient factors� Kidney factors

Nephrotoxic AKI Risk – Patient Factors

M Perazella , Clin J Am Soc Nephrol 2018; 13(12): 1897-1908

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Nephrotoxic AKI – Drug Factors


Nephrotoxic AKI – Kidney Factors


Nephrotoxic AKI Risk - Drug


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AKI – Nephrotoxic Medications

Nephrotoxic AKI

Nephrotoxic AKI

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BIOMARKERS

Biomarkers in AKI

P Murray et al, Kidney Int 2014; 859(3): 513-521

Biomarkers in AKI


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Biomarkers in AKI – Serum Creatinine

Bennett et al, Clin J Am Soc Nephrol 2008; 3: 665-673

Biomarkers in AKI


Biomarkers in AKI – NGAL

Bennett et al, Clin J Am Soc Nephrol 2008; 3: 665-673

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Biomarkers in AKI - Nephrocheck

Biomarkers in AKI

L Forni et al, Kidney Intensive Care Med 2017; 43: 855-866

Biomarkers in AKI

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Can AKI Be Prevented??

AKI – Prevention

� Identify children at risk

� Correct / prevent hypovolemia:� Early fluid administration / resuscitation� Data supports approach in:

� Rhabdomyolysis, hemoglobinuria� Tumor lysis syndrome� Nephrotoxic medications (acyclovir, aminoglycosides, ampho-B)� Chemotherapy (cisplatin, MTX)� Radiocontrast

� Prevent nephrotoxic AKI:� Frequent monitoring of renal function when used� Frequent monitoring of drug levels� Early dose adjustment, drug class change(Nephrotoxic AKI increases with increased exposure (number of drugs, dose, and duration)

NINJA

Nephrotoxic-Injury Negated by Just-in-time Action

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NINJA

AKI – Nephrotoxic Medications

AKI – Prevention

� Quality improvement Study:� 1749 patients / 2356 admissions / 3243 nephrotoxic exposure /

170 patient (9.7%) – non-critically ill� Using EMR algorithms to identify at risk patients:

� aminoglycoside x 3 days or more, or � 3 or more nephrotoxic meds for 3 days)

� Nephrotoxic exposure decreased by 38%� AKI incidence decreased by 64%

S Goldstein et al, Kidney Int 2016; 90(1): 212-221

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Clinical Approach to AKI

Step Evaluation

1. Volume status H&P, weight, UOP, fluid challenge

2. Obstruction? H&P, Foley, renal US

3. Renal function tests Chem panel, PO4, Hgb

4. Probable cause of AKI Evaluate for nephrotoxic exposure, hypovolemia, hypotension, drug levels

5. Urinalysis and microscopy SG, protein, blood, casts, cells, crystals

6. Urinary indices – FENa+ Spot urine for Na+ and Creatinine

7. Further tests Biomarkers, immune workup (GN), imaging, biopsy

Treatment of AKI

Specific Supportive

• Volume resuscitation• Correction of hypotension• Remove obstruction• Remove nephrotoxic agent• Sepsis treatment• Disease-specific therapy (GN,

pyelonephritis) – IMS

• Correction of electrolyte problems (K+, acidosis, PO4, Ca)

• Correction of hypervolemia (should not be an emergency)

• Fluid restriction??? Diuresis??• Nutrition• Correction of anemia• Dialysis (PD, HD, CRRT) – early

initiation in critically-ill• Drug dosing adjustment (for GFR

and for dialysis)

Fluid Overload in AKI

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Fluid Overload in AKI - Mortality

S Sutherland et al, Am J Kid Dis 2010; 55(2): 316-325

Dialysis in AKI

� When is dialysis indicated?� Fluid� Electrolyte� Other

� Goal of therapy? Supportive:� Provide optimal medications, nutrition, blood products,

electrolyte balance, without worsening fluid overload

� What modality?� Patient factors: Needs, anatomy, access� Center factors: Resources� No modality is better than the other

� How long?� Until kidneys get better

Dialysis in AKI

� Single center retrospective study� AKI post cardiac surgery (n = 480)� AKI within 72 hours:

� 23% in neonates, and 26% in children

� AKI was associated with:� Increased PICU LOS (12 vs 4 days, p < 0.001)� Increased hospital LOS (27 vs 14 days, p < 0.001)� Increased mortality (17.5% vs 3.7%, p < 0.01)

� Dialysis therapy (neonates 16% vs 3.8% in other, p < 0.01)� PD initiation < 24 hours associated with lower mortality vs

PD > 24 hours (25% vs 44%)� CRRT was associated with 28.6% mortality (2/7) (no

mortality in patients started on CRRT < 24 hours)

J Sanchez-De-Toledo et al, Pediatr Cardiol 2016; 37(4): 623-628

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Management – Follow up after AKI

L Chawla et al, Nature Rev Nephrol 2017; 13(4): 241-257

AKI - Summary

AKI - Conclusion

� AKI is bad:� Increased morbidity and mortality� Increased CKD� Increased cost

� Risk factors for increased mortality and morbidity:� Severity of AKI� Severity of fluid overload� Late initiation of RRT (dialysis)� Patient risk factors

� Nephrotoxic AKI can be prevented

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THANK YOU

Documents

Acute Kidney Injury (AKI) Recognition and Management in ......312 studies, 152 using KDIGO-AKI, 50 million episodes Pooled AKI incidence 21.6% in adults, 33.7% in children Pooled AKI