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Utility of Urinary [TIMP-2]*[IGFBP7]as a Predictor of Acute Kidney Injury

in Cardiac Surgery Patients

Paul L. DiGiorgi, MD, FACSShipley Cardiothoracic Center

HealthPark Medical CenterFort Myers, Florida

Association of Physician Assistants in

Cardiothoracic and Vascular Surgery37th Annual Meeting

April 2018

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Disclosures:

None

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter, Suppl. 2012; 2:1-138Tolwani A. Continuous Renal-Replacement Therapy for Acute Kidney Injury. N Engl J Med. 2012;367:2505-2514.

What is Acute Kidney Injury?

Acute injury with associated functional decrease.

Relatively Common in Cardiac Surgery

[1] Mehta et al. Circuation 2006[2] Lagny MG et al, BMC Nephrology. 2015;16:76[3] Hobson et al. Circulation. 2009;119:2444-2453

• Published AKI rates2,3: ~50%

• STS renal failure rate1: 1-5%

• Associated with significant complications:

• Death

• Stroke

• Bleeding

• Pneumonia

• Wound infection

• Multisystem organ failure

• Length of stay / Readmission

• Costly

Worse Long Term Survival afterCardiac Surgery

Hobson et al. Circulation. 2009;119:2444-2453

Worse Survival even with Recovery

Hobson et al. Circulation. 2009;119:2444-2453

Readmission Rates after Cardiac Surgery

Brown JR et al. Impact of perioperative acute kidney injury as a severity index for thirty-day readmission after cardiac surgery. Ann Thorac Surg. 2014;97(1):111-7.

N=2,209

* AKI by creatinine definition

Financial Impact of AKI after Cardiac Surgery

Alshaikh, HN et al. Ann Thorac Surg 2018 Feb;105(2):469-475

• 2008 – 2011 National Inpatient Sample database• CABG and/or valve replacement operations• AKI captured by ICD diagnosis• Total patients: 1,267,383• AKI rate about 10%

Financial Impact of AKI after Cardiac Surgery

Alshaikh, HN et al. Ann Thorac Surg 2018 Feb;105(2):469-475

• 2008 – 2011 National Inpatient Sample database• CABG and/or valve replacement operations• AKI captured by ICD diagnosis• Total patients: 1,267,383• AKI rate about 10%

Risk Factors

O’Neal et al. Critical Care (2016) 20;187

Can Early Identification Stop Progression?

Figure adapted from: [1] Lewington AJP, Certa J, Mehta RL Raising Awareness of Acute Kidney Injury: A Global Perspective of a Silent Killer. Kidney Int. 2013;84(3):457-467.[19] Kellum JA, Chawla LS. Cell-Cycle Arrest and acute kidney injury: the light and dark sides. Nephrol Dial Transplant. 2016;1:16-22

Kidney stress is a precursor for AKI19

Discovery & Validation of [TIMP-2]*[IGFBP7]Nephrocheck (NC)

[27] Kashani K, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care.

2013;17:R25.

[28] Bihorac A, et al. Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication. Am J

Respir Crit Care Med. 2014;189(8):932-939.

Use and Intervention associated with lower rates of AKI

Meersch et al. 2017. Intensive Care Med : Prevention of cardiac surgery-associated AKI by implementing the

KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial.

N=276

HealthPark Study

• September 2015 – October 2016• Cardiac surgery patients only, ESRD excluded• Baseline creatinine = closest to OR (STS)• NC drawn 4-12 hrs after entry into OHICU• Peak creatinine @ 24 hrs postop• Peak creatinine recorded for hospitalization• Hourly UO recorded while in ICU• KDIGO guideline management on all patients

Methods

• NC recorded, considered positive for > 0.3• AKI determined per KDIGO guidelines• Calculated STS RF rate, O:E ratio• Compared AKI rates before and after NC begun• NC results report all cases• Risk scores, outcomes reported from STS db

Results

Total patients: 1116 (STS+TVT), STS 1015

Male (%) 73

BMI 29

Age (years) 69

Diabetic (%) 41

HTN (%) 85

Baseline creatinine (Crs) 1.14

Emergent (%) 4

CPB (min) 106

Aortic crossclamp (min) 77

Isolated CABG (%) 50

TAVR (%) 12

Transfusion (%) 40

Results

No AKI (673) AKIany (342) p-Values

30-Day Mortality (%) 2.8 5.3 0.07

Length of Stay (days) 6.7 7.8 <0.01

Readmission (%) 16.9 19.3 0.36

N=1,015*

*STS Adult Cardiac Database

NC level AKIany AKICr

+NC = 2.0+ 50% 23%

+NC 1.4-1.99 30% 5%

+NC 0.31-1.39 18% 4.7%

Higher NC levels increase likelihood of AKI

N=1,116

PPV of AKI at different NC levels

The Negative NC

Negative predictive value for any AKI: 77%

0

20

40

60

80

100

120

AKI

False Negative NC

Total UO only UO/Cr @ 24hr UO/Cr LOS

• *When drawn at 24 hours• Vast majority were diagnosed by UO only

Creatinine may be better than UOin Cardiac Surgery Patients

Lagny et al. BMC Nephrology (2015) 16:76

N=443

Results: RF and AKI

AKI (UO & Cr @24hr) AKI (UO & Crpeak)

AKI (all) (n, %) 343, 31% 373, 34%

AKI stage 1 (n, %) 178, 16% 193, 17%

AKI stage 2 (n, %) 152, 14% 165, 15%

AKI stage 3 (n, %) 13, 1% 22, 2%

Observed Expected O:E

Renal Failure Risk(Isolated CABG, STS)

0.35% 4.25% 0.08

Results: NC implementation impact*

Pre NC (863) Post NC (1116) p-Value

All creat AKI (n, %) 88, 10% 77, 7% 0.01

AKI stage 1 (n, %) 45, 5% 45, 4%

AKI stage 2 (n, %) 25, 3% 20, 2%

AKI stage 3 (n, %) 18, 2% 12, 1%

Renal Failure Expected Risk (STS)

4.9% 4.7%

*AKI defined by creatinine change only

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

Stage 1 AKI Stage 2 AKI Stage 3 AKI

Pe

rce

nt

of

card

iac

surg

ery

pat

ien

ts

Pre-NephroCheck(N=863)

Post-NephroCheck(N = 1116)

22.7%reduction

38.1%reduction

48.4%reduction

p = 0.01 for reduction of combined stage 1,2,3 AKI (32.3% reduction)

Data presented at Multidisciplinary Cardiovascular and Thoracic Critical Care Conference, 10/6/17

BigPAK RCT NephroCheck-Indicated KDIGO Protocol

Median ICU LOS decreased by 1 day (p = 0.035)P

rop

ort

ion

of

pat

ien

ts r

emai

nin

g in

th

e IC

U (

%)

Days in ICU

Proportion of patients remaining in ICU

Control (Standard care)

Intervention

0%

5%

10%

15%

20%

25%

Control Intervention

Pati

ents

Wit

h M

od

erat

e-Se

vere

AK

I Wit

hin

7 D

ays

(%)

Moderate-Severe AKI (7 days)

66.1% reductionp = 0.035

Göcze I, Jauch D, Götz M, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BiK Study. Ann Surg. Published online August 2017.

• 66% Reduction In Stage 2-3• ICU LOS Reduction• >$2000 Cost Savings per patient

PrevAKI RCT NephroCheck-Indicated KDIGO Protocol

Using Stress Biomarkers to Avoid AKI

• Avoidance of early ACEI/ARBs, toradol

• Glycemic control

• Optimizing hemodynamics

• Potential slow weaning of drips, delayed transfer from ICU

• Perioperative vancomycin dosing adjustment

• Start diuretics > 24 hours

Postoperative Management

Good UO/hemodynamics

Typical Case Scenarios

MarginalUnstable / on

significant support

+ NC - NC + NC - NC

Transfer out Transfer out

Delay transfer, optimize

• AKI has long term implications even if creatinine normalizes

• Early urine output importance unclear in postop patient

• Outcomes are becoming more and more scrutinized

• AKI potentially avoidable with early stress identification

• Biomarkers may be helpful if properly interpreted and acted upon

• Preoperative optimization impacts postoperative outcomes

Conclusions

Thank You