Drug Induced Kidney Injury: Prevention and Management ......8 Centers 58% 9 Centers 60% 62% 65% 74% 10 Centers (JH) 76% 11 Centers (Wisconsin) 82% 76% 84% 57 Med list Missing Wisc

The Center for Acute Care Nephrology

Drug Induced Kidney Injury:Prevention and Management Strategies

Stuart L. Goldstein, MDClark D. West Endowed Chair

Professor of Pediatrics

University of Cincinnati College of Medicine

Director, Center for Acute Care Nephrology

Medical Director, Pheresis Service

Cincinnati Children’s Hospital Medical Center



Conflicts of Interest• Baxter Healthcare

• Speaker’s Bureau• Grant support• Consultant

• Consultant• AM Pharma• Astute Medical• Bioporto• Fresenius• MediBeacon• Medtronic• Reata• Renibus


High Level Rationale for NINJA

• One of the most common causes of AKI in non-critically ill hospitalized children

• A portion of NTMx-AKI goes unnoticed due to lack of systematic kidney function surveillance in exposed children

• Multiple studies show SCr measured at least every four days only 50% of the time in children receiving multiple NTMx

• NTMx-AKI may be a potentially modifiable adverse safety event if• At-risk patients are identified• Systematic SCr monitoring is instituted reliably in at-risk patients• AKI is avoided and/or mitigated by reducing unnecessary NTMx exposure


NINJA Vision Statement

Children should only get the nephrotoxic medications they need

for the duration they need them


• Patients receiving IV AG > 5 days• Primary renal diagnoses excluded• One year of study

• 557 children• 95% > 3 months of age• AKI occurred in

• SCr measured at least q4 days only 50% of the time


• 350 non-critically ill children with AKI by pRIFLE• 350 matched children without AKI• 38 potential NTMx• Compared NTMx exposure rate between AKI vs. non-

AKI patients• 86% exposed to at least 1 NTMx• Patients with AKI had 1.7 OR for exposure to a NTMx• PPV for AKI doubles for patient with 3+ NTMx


Background

Nephrotoxic medication (NTMx)-associated Acute Kidney Injury (AKI) is one of the most common causes of AKI in hospitalized children.


Background


Recent studies demonstrate that NTMx-AKI occurs at higher than previously recognized rates.


Background



A portion of NTMx-AKI goes unnoticed due to lack of kidney function surveillance in susceptible children.


Background



A portion of NTMx-AKI goes unnoticed due to lack of kidney function surveillance in susceptible children.


Objectives of NINJA

• Develop and EHR-based AKI screening intervention to assess changes in AKI prevalence, or duration (intensity)

• RELIABLY QUANTIFY the rate of High NTMx exposure and NTMx-AKI in the non-critical care population.


High NTMx-exposure Criteria

Patient receiving 3 or more nephrotoxic medications (NTMx) concomitantly*

orOn an aminoglycoside for 3 or more days

*IV radiology contrast, amphotericin, or cidofovir in previous week is counted for the week following administration


Nephrotoxic Medication List


AKI Definition


Outcome Measures


The Process

Pharmacists create/receive daily reports,

verify & validate

Provide SCr screening

suggestions if necessary

Data Analyst compiles

registry from Pharmacist reports…

…and generate

metrics, run charts

Share with AKI team,

leadership, other

stakeholders


AKI Surveillance Algorithm

Meets High NTMx Exposure Criteria

Exposure surveillance loop

Injury surveillance loop

End Surveillance




Inclusion Flowchart

Data span June 2, 2011 – June 4, 2012

99% compliance with daily SCrmonitoring in all

high NTMx-exposed patients



Initial AKI prevalence rates 10-fold higher than CAUTI rates and 3-fold higher than CLBSI rates at CCHMC


AKI intensity decreases in Year 1 of the project by 42%




Measure 2011* 2012 2013 2014 2015* Aggregate Annualized Non-Critically Ill Patient Days (Actual Count)

97,065

(26,133)

91,363

90,627

99,076

109,968 (27,492)

334,691 Census Days

Annualized Number Of Patient Exposures (Actual Count)

1,129 (304)

969 837 960 692 (173)

3,243 Patient Exposures

Annualized Number Of Patients With AKI (Actual Count)

271 (73)

168 141 159 116 (29)

575 Patients With AKI

Patient Exposures Avoided N/A 108 200 219 106 633 Avoided Exposures

Patients With AKI Avoided

N/A 105 113 134 46 398 Avoided AKI Events

*Data presented for partial year. Annualized values represent if data were extrapolated to full time period. Study period in 2011 (Sept – Dec), in 2015 (January – March). All aggregate data are actual count.

Adverse Events Avoided


Cost Implications – A Theoretical Model

• Costs incurred• Daily creatinine• Prolonged hospital admission for AKI detection• Follow up clinic and labs since AKI detected• Medications to slow CKD progression

• Potential cost savings (earlier detection)• AKI avoided• CKD avoided• ESRD avoided



7 Cen

ters

56%

8 Cen

ters

58%9 C

enter

s

60%NC

H Or

lando

62%

65%

74%

10 C

enter

s (JH

)

76% 11 C

enter

s (W

iscon

sin)

82%

76% 84%

57 M

ed li

st

84%

7.857.39

Miss

ing W

isc. d

ata

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Expo

sure

Rate

The Rate of Patients with Nephrotoxic Medication (NTMx) Exposure per 1000 Non-ICU Patient Days

High NTMx Exposure Rate Average High NTMx Exposure Rate Control Limits

Maturity Detection System

All Centers



7 Cen

ters

56%

8 Cen

ters

58%

9 Cen

ters60%

NCH

Orlan

do

62%65%

74%

10 C

enter

s (JH

)

76%

11 C

enter

s (W

iscon

sin)

82%

76%84%

57 M

ed lis

tMi

ssing

Wisc

. data

84%

1.62

1.25

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

AKI R

ateRate of Nephrotoxic Medication (NTMx) associated

Acute Kidney Injury (AKI) per 1000 Non-ICU Patient Days

AKI Rate Average AKI Rate Control Limits


All Centers



8 Cen

ters

58%

9 Cen

ters

60%

62%

65%

74%

10 C

enter

s (JH

)

76%

11 C

enter

s (W

iscon

sin)

82%

76%

84% 57 M

ed lis

tMi

ssing

Wisc

. data

84%20.8

15.0

0

5

10

15

20

25

30

35

40

Perce

nt wi

th AK

IPercent of patients with Nephrotoxic Medication (NTMx) Exposure

who develop Acute Kidney Injury (AKI)

BiMonthly Percent with AKI Average Percent of Patients with AKI Control Limits

All Centers

%



7 Cen

ters

56%

8 Cen

ters

58%

9 Cen

ters

60%

NCH

Orlan

do 62%

65%

74%

10 C

enter

s (JH

)

76%

11 C

enter

s (W

iscon

sin)

82%

76%

84%

57 M

ed lis

tMi

ssing

Wisc

. data

84%

10.9

0.0

5.0

10.0

15.0

20.0

25.0

30.0

AKI D

ays

Acute Kidney Injury (AKI) Days per 100 High NTMx Exposure Days

AKI Days Average AKI Days Control Limits


All Centers


NINJA has been accepted as the next Hospital Acquired Condition

to be spread across the Solutions for Patient Safety


Vision for NINJA

• Develop reliable AKI detection and mitigation across the collaborative

• Once the clinical NINJA engine is in place, this reliable NTMx-AKI phenotype will allow for:

• Disease specific epidemiology and AKI reduction strategies• Development of translational research initiatives

• Pharmacogenomics• AKI biomarker validation• Personalized AKI detection and reduction strategies


Alig

nmen

t with

CF

Lead

ersh

ip -

Nov

Proj

ect K

ick

off M

eetin

g -D

ec

Stee

ring

Team

For

med

-Ja

nuar

y'AK

I Aw

aren

ess

for C

F Te

am

CF

Wor

king

Tea

m F

orm

ed

Hyd

ratio

n be

fore

NTM

x

17.3910.56%

0%

20%

40%

60%

80%

100%Pe

rcen

t with

AK

I

Quarterly

Percent of CF Patient with High NTMx exposure devloping AKI

Percent of patients with AKI Average Percent of patients with AKI Control Limits

(Using P chart)

Hospital Rate = 15.4%

(Using μ chart)


Beg

in A

utom

atai

c Tr

igge

r Rep

ort

Alig

nmen

t with

CF

Lead

ersh

ip -

Nov

Proj

ect K

ick

off M

eetin

g -D

ec

CF

Wor

king

Tea

m F

orm

ed

Stee

ring

Team

For

med

-Ja

nuar

y'AK

I Aw

aren

ess

for C

F Te

am

Hyd

ratio

n be

fore

NTM

x

5.26

2.93

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

Inte

nsity

Rat

e

Quarterly

AKI Days per 100 High-NTMx Exposure Days in CF Patients (Intensity)

Quarterly Intensity Rate AverageRate Control Limits

(Using μ chart)

Hospital Rate = 19.13/100 Days


Next for NINJA

• Accepted by the Solutions for Patient Safety as the next Hospital Acquired Condition

• Use NINJA as the foundation for more translational work

• Risk stratification• Biomarker integration• Sub-population assessment








Contr

ast P

rotec

tion P

rotoc

olPh

arma

cist R

ound

ing/N

TMx I

mpac

t Aler

t

Vanc

omyc

in St

ewar

dship

Phar

macy

Sma

rtPhr

ase

Cefep

ime v

s Zos

yn16.08

11.19

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

Jul-1

3Au

g-13

Sep-

13Oc

t-13

Nov-1

3De

c-13

Jan-

14Fe

b-14

Mar-1

4Ap

r-14

May-1

4Ju

n-14

Jul-1

4Au

g-14

Sep-

14Oc

t-14

Nov-1

4De

c-14

Jan-

15Fe

b-15

Mar-1

5Ap

r-15

May-1

5Ju

n-15

Jul-1

5Au

g-15

Sep-

15Oc

t-15

Nov-1

5De

c-15

Jan-

16Fe

b-16

Mar-1

6Ap

r-16

May-1

6Ju

n-16

Jul-1

6Au

g-16

Sep-

16Oc

t-16

Nov-1

6De

c-16

Jan-

17Fe

b-17

Mar-1

7

High

NTM

x Exp

osur

e Pat

ients

Monthly

High NTMx Exposured Patients per 1000 Patient Days Oncology/Hematology Patients

Monthly High NTMx Exposure Patients Average Monthly High NTMx Expsoure Rate Control Limits

(Hospital Rate - 7.5/1000 Days)


Contr

ast P

rotec

tion P

rotoc

olPh

arma

cist R

ound

ing/N

TMx I

mpac

t Aler

t

Vanc

omyc

in St

ewar

dship

Phar

macy

Sma

rtPhr

ase

Cefep

ime v

s Zos

yn16.08

11.19

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

Jul-1

3Au

g-13

Sep-

13Oc

t-13

Nov-1

3De

c-13

Jan-

14Fe

b-14

Mar-1

4Ap

r-14

May-1

4Ju

n-14

Jul-1

4Au

g-14

Sep-

14Oc

t-14

Nov-1

4De

c-14

Jan-

15Fe

b-15

Mar-1

5Ap

r-15

May-1

5Ju

n-15

Jul-1

5Au

g-15

Sep-

15Oc

t-15

Nov-1

5De

c-15

Jan-

16Fe

b-16

Mar-1

6Ap

r-16

May-1

6Ju

n-16

Jul-1

6Au

g-16

Sep-

16Oc

t-16

Nov-1

6De

c-16

Jan-

17Fe

b-17

Mar-1

7

High

NTM

x Exp

osur

e Pat

ients

Monthly

High NTMx Exposured Patients per 1000 Patient Days Oncology/Hematology Patients

Monthly High NTMx Exposure Patients Average Monthly High NTMx Expsoure Rate Control Limits

(Hospital Rate - 7.5/1000 Days)


Contr

ast P

rotec

tion P

rotoc

olPh

arma

cist R

ound

ing N

TMx I

mpac

t Aler

t

Vanc

omyc

in St

ewar

dship

Phar

macy

Sma

rtPhr

ase

Cefep

ime v

s Zos

yn

3.48

1.92

0.0

2.0

4.0

6.0

8.0

10.0

12.0Ju

l-13

Aug-

13Se

p-13

Oct-1

3No

v-13

Dec-1

3Ja

n-14

Feb-

14Ma

r-14

Apr-1

4Ma

y-14

Jun-

14Ju

l-14

Aug-

14Se

p-14

Oct-1

4No

v-14

Dec-1

4Ja

n-15

Feb-

15Ma

r-15

Apr-1

5Ma

y-15

Jun-

15Ju

l-15

Aug-

15Se

p-15

Oct-1

5No

v-15

Dec-1

5Ja

n-16

Feb-

16Ma

r-16

Apr-1

6Ma

y-16

Jun-

16Ju

l-16

Aug-

16Se

p-16

Oct-1

6No

v-16

Dec-1

6Ja

n-17

Feb-

17Ma

r-17

AKI P

atien

ts

Monthly

AKI associated with High NTMX Exposure Rate per 1000 Patient Days Oncology/Hematology Patients

Monthly AKI Patients Average Monthly AKI Rate Control Limits

(Hospital Rate - 1.06/1000 days)


Contr

ast P

rotec

tion P

rotoc

ol Ph

arma

cist R

ound

ing; N

TMx I

mpac

t Aler

t

Vanc

omyc

in St

ewar

dship

Phar

macy

Sma

rtPhr

ase

Cefep

ime v

s Zos

yn

21.61

0%

20%

40%

60%

80%

100%Ju

l/13

Aug/1

3Se

p/13

Oct/1

3No

v/13

Dec/1

3Ja

n/14

Feb/1

4Ma

r/14

Apr/1

4Ma

y/14

Jun/1

4Ju

l/14

Aug/1

4Se

p/14

Oct/1

4No

v/14

Dec/1

4Ja

n/15

Feb/1

5Ma

r/15

Apr/1

5Ma

y/15

Jun/1

5Ju

l/15

Aug/1

5Se

p/15

Oct/1

5No

v/15

Dec/1

5Ja

n/16

Feb/1

6Ma

r/16

Apr/1

6Ma

y/16

Jun/1

6Ju

l/16

Aug/1

6Se

p/16

Oct/1

6No

v/16

Dec/1

6Ja

n/17

Feb/1

7Ma

r/17

Perc

ent w

ith A

KI

Monthly

Percent of High NTMx Exposed Patients with AKI Oncology/Hematology Patients

Monthly Percent of patients with AKI Average Percent of patients with AKI Control Limits

(Using P chart)

%

(Hospital Rate - 15.4%)


Contr

ast P

rotec

tion P

rotoc

ol Ph

arma

cist R

ound

ing; N

TMx I

mpac

t Aler

t

Vanc

omyc

in St

ewar

dship

Phar

macy

Stew

ards

hip

Cefep

ime v

s Zos

yn

34.30

5.350.0

20.0

40.0

60.0

80.0

100.0

120.0

140.0

160.0

180.0

200.0

Jul-1

3Au

g-13

Sep-

13Oc

t-13

Nov-1

3De

c-13

Jan-

14Fe

b-14

Mar-1

4Ap

r-14

May-1

4Ju

n-14

Jul-1

4Au

g-14

Sep-

14Oc

t-14

Nov-1

4De

c-14

Jan-

15Fe

b-15

Mar-1

5Ap

r-15

May-1

5Ju

n-15

Jul-1

5Au

g-15

Sep-

15Oc

t-15

Nov-1

5De

c-15

Jan-

16Fe

b-16

Mar-1

6Ap

r-16

May-1

6Ju

n-16

Jul-1

6Au

g-16

Sep-

16Oc

t-16

Nov-1

6De

c-16

Jan-

17Fe

b-17

Mar-1

7

AKI D

ays

Monthly

AKI Days per 100 High-NTMx Exposure Days (Intensity) Oncology/Hematology Patients

Monthly AKI Days Mean Monthly AKI Days Control Limits

(Hospital Rate -19.13/100 Days)


Can NINJA work in the ICU?


So….. CAN NINJA WORK IN THE ICU?• NO!

• NINJA raised awareness of NTMx-AKI by increasing surveillance in at-risk non-ICU patients

• AKI risk is already high in the ICU• Aren’t we already monitoring for AKI daily anyway in the ICU?• Don’t all ICU patients get at least 3 NTMx the femptosecond they roll

in the door?

• MAYBE!• Are pharmacists in the ICU armed and supported to

• Make medication recommendations/dosing adjustments based on risk?

• Highlight the need to minimize “unnecessary” NTMx?• Look up organism antimicrobial susceptibility?


Acknowledgements

• Eric Kirkendall, MD, MBI• Stephen Muething, MD• Theresa Mottes, RN, BSN• Devesh Dahale• Cynthia Barclay, PharmD

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCN-vndLMlcgCFUqGDQodhSIGKw&url=http://axialexchange.com/blog/article/an-overview-of-the-ahrq-patient-engagement-guide&psig=AFQjCNEG6Adi6L6jNenRdhIUD9xdt804Pw&ust=1443387780746563

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCN-vndLMlcgCFUqGDQodhSIGKw&url=http://axialexchange.com/blog/article/an-overview-of-the-ahrq-patient-engagement-guide&psig=AFQjCNEG6Adi6L6jNenRdhIUD9xdt804Pw&ust=1443387780746563

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCKm68fPMlcgCFUePDQodsdQMzw&url=http://rwbexp.com/&psig=AFQjCNEy7wMZec-_F8fKvzzXGaAUg01uDQ&ust=1443387842476489

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCKm68fPMlcgCFUePDQodsdQMzw&url=http://rwbexp.com/&psig=AFQjCNEy7wMZec-_F8fKvzzXGaAUg01uDQ&ust=1443387842476489


Documents

Drug Induced Kidney Injury: Prevention and Management ......8 Centers 58% 9 Centers 60% 62% 65% 74% 10 Centers (JH) 76% 11 Centers (Wisconsin) 82% 76% 84% 57 Med list Missing Wisc