Secondary a nd Tertiary Prevention of

AKI
Michael Heung MD
University of Michigan
mheung@umich.edu ASN
@keepingitrenal

Disclosures
• No relevant conflicts of interest

• Grant Funding: VA, NIDDK, CDC, PCORI, Baxter Inc

• Consultant: Baxter Inc., Potrero Medical Inc., Lexicomp

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Objectives
• Describe opportunities to limit complications of AKI

• Describe opportunities to improve

outcomes among survivors of AKI

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Prevention - Definitions
Primary: avoid the disease

Secondary: limit damage/complications

Tertiary: improve outcomes with established disease

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 Conceptual Model

Full Recovery
Prevention

Prevention
Prevention
Secondary
Primary

Tertiary
Severe AKI Partial recovery CKD

Non-Recovery ESRD

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AKI Survivorship

Trends in Severe (Dialysis-Requiring)

AKI
AKI-D In-Hospital Mortality

aOR 0.60 (0.56-0.67)

10% annual increase

Hsu et al, JASN 2013;24:37-42 Brown et al, Am J Nephrol 2016;43:261-70

ASN Increasing AKI-D + Improved mortality = More AKI Survivors

 AKI Survivorship

• AKI survivors remain at high risk for adverse outcomes

• Renal: CKD, ESRD, recurrent AKI

Secondary prevention
• Cardiovascular: HTN, CHF, CAD

• Quality of life
Tertiary prevention
• All-cause mortality

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What Dr. Siew Just Told Us

• AKI and CKD are intertwined

• KDIGO 2012 AKI guidelines: 2.3.4 Evaluate patients 3

months after AKI for resolution, new onset, or

worsening of pre-existing CKD (not graded)

• But can we do anything about it?

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 General Approach
Early: Limit AKI severity using KDIGO “bundle”
• Hemodynamic optimization
• Avoiding nephrotoxic exposures

Later: ADQI 22* “KAMPS” approach

• Kidney function check
• Advocacy: education around AKI and CKD risk
• Medication reconciliation (prescribed and OTC)
• Blood Pressure monitoring and treatment
ASN • Sick day protocols
*Kashani et al, CJASN 2019;14:941-53

Emerging Therapies
No Spironolactone
• AKI leads to a pro-inflammatory state
and contributes to development of CKD

• Barrera-Chimal (2012): In rat model,

spironolactone attenuated the risk of Spironolactone
CKD after ischemic AKI
No Sp

• Clinicaltrials.gov – 4 trials (3 Mexico, 1

Iraq), all AKI prevention focus Sp
Controls
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Barrera-Chimal et al, Kidney Int 2012;83:93-103

 Lithium?
• Implication of glycogen synthase kinase 3ß
(GSK3ß) in pathogenesis of AKI

• Bao (2014): In mouse models of cisplatin

and ischemic AKI, single dose of Li led to
faster renal recovery, less histologic injury,
more evidence of tubular proliferation

• Clinicaltrials.gov – 1 phase 4 study

(not updated)
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Bao et al, JASN 2014;25:488-500

NAM (Vit B3)?

• Mehr (2018): In mice, found lower
levels of renal NAD after isch AKI
• Higher AKI risk with QPRT
deficiency, rescued by NAM
• Phase 1 PRCT in patients
undergoing cardiac surgery (n=55)
• Well-tolerated
• Led to higher NAM, NMN levels
ASN • Associated with lower AKI risk
Poyan Mehr, Nature Med 2018;24:1351-9
 AKI Survivorship

• AKI survivors remain at high risk for adverse outcomes

• Renal: CKD, ESRD, recurrent AKI

Secondary prevention
• Cardiovascular: HTN, CHF, CAD

• Quality of life
Tertiary prevention
• All-cause mortality

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Post-AKI Mortality
HR 0.76
• Harel (2013): Cohort of AKI-D pts (0.62-0.93)
that survived 90d after
hospitalization (n=1184)
• Propensity-matched comparison of
early neph f/u (visit within 90d)
versus no f/u
• Nephrology follow-up associated
with significantly lower long-term
all-cause mortality

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Harel et al, KI 2013;83:901-8
 Audience Response Question
Of your patients with AKI-D who survive to hospital discharge and
are non-dialysis-dependent, what proportion have nephrology
follow-up within 3 months after discharge?

A. <25%
B. 25-49%
C. 50-74%
D. >75%
E. I have no idea
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CJASN 2019;14:941-53

Consensus Statement: Health care systems need to quantitate

the proportion of patients who need post-AKI/AKD follow-up,
those who receive any post-AKI/AKD follow-up, and evaluate
quality of care for those who received post-AKI/AKD follow-up

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ASN
Kashani et al, CJASN 2019;14:941-53

AKI Follow-up: Opinion vs Reality!

• Survey of 145
Canadian
nephrologist
s

• Among AKI
patients that
nephrologists
thought should get
follow-up, only 24%
were actually seen

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Karsanji et al, CJASN 2017;12:1753-61
 The AKD-D Patient
• Between 10-30% of AKI-D survivors will remain dialysis-
dependent at the time of hospital discharge

• Previously patient placement was difficult and required hospital-

based monitoring or ESRD certification
• As of 1/1/2017, AKI-D patients can receive dialysis at
ESRD facilities (“Trade Bill”)

• How can we optimize outcomes in these patients?

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ESRD Recovery Incidence of

Renal Recovery

• Lee (2018): Marked increase in

ESRD recovery
• AKI misclassification?
• Leveling off after 2012

“One might speculate that even

more patients with ‘ESRD’ could
have recovered but did not because
they were not appropriately treated
ASN and monitored”
Lee et al, AJKD 2018;72:311-3
 Audience Response Question
Among patients with AKI-D (and no pre-existing CKD) who survive to
hospital discharge and still require dialysis, what proportion can be
expected to subsequently recover to dialysis-independence?

A. 10% or less
B. 15-25%
C. 30-40%
D. 50-60%

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Michigan Experience
• Retrospective cohort of AKI pts requiring outpatient dialysis (n=100)
• At 90 days follow-up: 43% recovered off-RRT, 48% ESRD
Recovery by Cause of AKI
Recovery by Baseline Renal Function
70
70
60
60
50
50
40
40
30
30
20 20
10 10
0 0
No CKD Stage 3 Stage 4 Stage 5 Sepsis ATN HRS/CRS Other
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N= 43 38 13 2 N = 13 55 11 21

Pajewski et al, Hemodial Int 2018;22:66-73

 Other Programs
• Hickson (AJKD 2015): Mayo Clinic (n=281)
• 17% recovery by 6 months
• 50% recovery in pts without pre-existing CKD
• Pts treated in specific center, non-ESRD protocols

• Gautam (Nephron 2015): UVA (n=119)

• 42% recovery overall
• Median recovery time 36.5 days
• Dedicated therapeutic extra-corporeal care unit
ASN (TECU) developed in response to CMS clarification 2012

What Are Best Practices?

• Full disclosure: we don’t really know!

• Very limited data for outpatient setting

• Starting point: AKI dialysis = ESRD dialysis

• Need individualized vs protocolized approach

• Appropriate hand-off and expectations

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 Monitoring for Renal Recovery
• Importance of active surveillance

• Who?
• Patient and care team
• How?
• Clinical and biochemical criteria

• How often?
• At least weekly, particularly in the early period
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Fluid Management

• ESRD: Establishment of “dry weight” via “challenges”

• Dry weight defined as the point below which patient
becomes symptomatic (hypotensive and/or cramping)
• Although some more objective criteria exist (e.g.
bioimpedance, real-time hematocrit sensing), these have not
supplanted clinical approach

• AKI: Focus on avoiding complications of fluid overload while

avoiding intradialytic hypotension
ASN • Ischemic insults may delay/impair renal recovery
 Outpatient Dialysis Care

• Focusing on 1st week of AKI-D outpatient dialysis:

Recovery Non-Recovery
Variable P-value
(n=43) (n=57)
Total fluid removal (L) 4.1 (2.9) 5.3 (2.7) 0.037
Ultrafiltration rate
4.7 (3.2) 6.0 (3.2) 0.041
(mL/kg/hr)
Hypotension
9.3% 24.6% 0.049
(>3 episodes of SBP<90)
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Pajewski et al, Hemodial Int 2018;22:66-73

ADQI 22: “WATCH-ME” Bundle

Weight Assessment: “permissive hypervolemia”
Access: vein preservation
Teaching: patients and providers
Clearance: assess underlying kidney function
Hypotension: avoiding intradialytic hypotension
MEdications: medication reconciliation

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Kashani et al, CJASN 2019;14:941-53
 Audience Response Question
When providing care for patients with AKI-D in the outpatient
setting, does your facility:

A. Primarily follow ESRD hemodialysis protocols

B. Have separate established protocols/procedures for AKI
patients

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Summary and Key Take-Aways

• Beyond initial AKI survival, patients remain at significant risk
for adverse outcomes – which is an opportunity for us to
intervene

• Post-AKI follow-up is important, especially in severe AKI

• Patients with AKD-D are a particularly vulnerable population,

and require close monitoring for renal recovery

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