3. AKI
eeded a Better Way to Assess AKI
eeded a Better Way to Monitor Kidney Stress In Real
ime
se of ScR and Urine Output is Too Slow and Lagging
ncreasing Biomarker Presence In Clinical Care
KI Is Expensive and Has Negative Effect on Metrics
nd Patients!!
ighly correlated with M & M; LOS, Cost
ome cases are preventable!!
4. AKI Is Common And Deadly: Pneumonia
*Genetic and Inflammatory Markers of Sepsis (GenIMS) study.
[1] Murugan R, Karajala-Subramanyam V, Lee M, et al. Acute Kidney Injury in Non-Severe Pneumonia is Associated with an Increased Immune Response and Lower Survival. Kidney Int.
2010;77:527-535.
AKI was found to be prevalent (34%) in a study of 1836 hospitalized patients with
community acquired pneumonia*,1
Severe AKI (n = 189, 10%)
Moderate AKI (n = 135, 7%)
Mild AKI (n = 307, 17%)
No AKI (n = 1205, 66%)
Mortality in
Hospitalized
Patients (%)
5. AKI Is Common And Deadly: Sepsis
Sepsis was identified as the presumed etiology in 19% of AKI cases in the ICU in one
study2 and septic shock was found to be a contributing factor to AKI in 48% of cases
in another study.3
Hospital
Mortality3
[2] Mehta RL, Pascual MT, Soroko S, et al. Spectrum of Acute Renal Failure in the Intensive Care Unit: the PICARD Experience. Kidney Int. 2004;66:1613-1621.
[3] Uchino S, Kellum JA, Bellomo R, et al. Acute Renal Failure in Critically Ill Patients: a Multinational, Multicenter Study. JAMA. 2005;294:813-818
28%
57%
0%
10%
20%
30%
40%
50%
60%
Sepsis Sepsis & AKI
6. AKI Is Common And Deadly: Major
Surgery (NSQIP data)
[15] Bihorac A et al. National Surgical Quality Improvement Program Underestimates the Risk Associated with Mild and Moderate Postoperative Acute Kidney Injury.
Crit Care Med. 2013;41(11):2570-2583.
0,6%
3%
7%
26%
0%
10%
20%
30%
No AKI Mild (Risk) Moderate
(Injury)
Severe
(Failure)
3%
6%
11%
29%
0%
10%
20%
30%
No AKI Mild (Risk) Moderate
(Injury)
Severe
(Failure)
Hospital Mortality 90-Day Mortality
single-center cohort of 27,841 adult surgical patients undergoing major surgery, it was identified
pital and 90-day mortality were significantly higher among patients with AKI compared to patients
no AKI.15
7. AKI IS PREVALENT IN CT SURGERY
[16] Hobson CE et al. Acute Kidney Injury is Associated with Increased Long-Term Mortality After Cardiothroacic Surgery. Circulation.
2009;119:2444-2453.
N = 2973 CT Surgery Patients16
0%
10%
20%
30%
40%
50%
60%
70%
80%
All Types Isolated CABG Valve Surgery Aortic Surgery Thoracic
Surgery
Heart
Transplant
%ofCTSurgerywithAKI
Moderate AKI Severe AKIMild AKINo AKI
7
8. [9] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter, Suppl. 2012; 2:1-138
[10]Tolwani A. Continuous Renal-Replacement Therapy for Acute Kidney Injury. N Engl J Med. 2012;367:2505-2514.
cute Kidney Injury (AKI) is a rapid (typically within about 48 hours) loss of kidney function9
• 96% of AKI does NOT require RRT10
IFLE/AKIN/KDIGO criteria were validated over the past decade and provide a standardized
efinition of AKI
he criteria are based on increases and serum creatinine and decreases in urine output and stratify
KI into three severity levels:9
1. Mild AKI (RIFLE-R or Stage 1)
2. Moderate AKI (RIFLE-I or Stage 2)
3. Severe AKI (RIFLE-F or Stage 3)
he criteria are good for epidemiological studies but difficult to apply at the bedside; AKI thus
emains largely a clinical diagnosis9
Recent Acute Kidney Injury (AKI) Definitions Have Helped
luminate The Burden Of AKI
9. AKI Identification In the ICU Can Be Inconsistent
[4] Massicottee-Azarniouch, Magder S, Goldberg P, Alam A. Acute Kidney Injury in the Intensive Care Unit: Risk Factors and Outcomes of Physician Recognition Compared with KDIGO Classification. Poster presented at: Society of Critical
Care Medicine; February 2016; Orlando, FL.
AKI Reported by ICU Staff No AKI Reported by ICU Staff
93 patients admitted to academic hospital ICU in Montreal, Canada from January 2006 through December 2011. KDIGO A
ulated from SCr values. Physician definition of AKI was determined by asking ICU staff if a patient had “acute renal failure
“ICU physicians only identified a small proportion of the patients with AKI. Many of the severe forms
of AKI, which were most associated with adverse outcomes, were missed by the physician reporting.”
79% of the cases
of Moderate and
Severe AKI Were
Not Identified by
Reporting
Physician
79% of the cases
of Moderate and
Severe AKI Were
Not Identified by
Reporting
Physician0
100
200
300
400
500
Moderate AKI Severe AKI
NumberofPatients
AKI as Classified by KDIGO Criteria vs
Physician Reporting
10. hout Better Tools, The Best Doctors Are Challenged With AKI
IS DEADLY, COSTLY, AND PREVALENT… AND LOCAL
2016 ANNUAL AKI DIAGNOSES6,7,8*
AVG COST
INCREASE /
PATIENT7
AVG LENGTH OF
STAY INCREASE /
PATIENT7
READMISSION RATE
INCREASE9
2200 ICU ADMISSIONS
476 ESTIMATED MODERATE/SEVERE ICU DIAGNOSES
$29,800 10.4 DAYS 15.9%
hough Often Under-reported5, AKI Hits Home:
Typical 500-Bed Hospital
$16.2 MILLION
COST INCREASE
5,450 DAYS
LENGTH OF STAY
INCREASE
86 PATIENTS
READMISSION INCREA
ANNUAL ICU IMPACT
MODERATE/SEVERE A
[5] Massicottee-Azarniouch, Magder S, Goldberg P, Alam A. Acute Kidney Injury in the Intensive Care Unit: Risk Factors and Outcomes of Physician Recognition Compared with KDIGO Classification. Poster presented at: Society of Crit
February 2016; Orlando, FL.
[6] American Hospital Directory Database, accessed Dec 2017 on 7,104 hospitals, data on file
[7] Hobson CE, Ozrazgat-Baslanti T, Kuxhausen A, et. al. Cost and Mortality Associated With Postoperative Acute Kidney Injury. Annals of Surgery. 2014;00:1–8
[8] SCCM: http://www.sccm.org/Communications/Pages/CriticalCareStats.aspx.
[9] 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
*Hospital AKI diagnoses from AHD Database adjusted for diagnoses in ICU using assumptions from SCCM (total US ICU admissions), and Hobson et al. (% moderate/severe AKI).
11. AKI IS A SPECTRUM OF KIDNEY DECLINE
AND EARLY IDENTIFICATION IS KEY TO
POTENTIALLY STOP THE PROGRESSION
11 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
Decreased Function
Asymptomatic Symptomatic (Diagnosis)
Kidney stress is a precursor for AKI19
12. SUBOPTIMAL DIAGNOSTIC TOOLS MAKE AKI
IMPROVEMENT DIFFICULT
12
igure adapted from: [1] Lewington AJP, Certa J, Mehta RL Raising Awareness of Acute Kidney Injury: A Global Perspective of a Silent Killer. Kidney Int.
013;84(3):457-467.
20] Martensson J et al. Novel Biomarkers of Acute Kidney Injury and Failure: Clinical Applicability. Brit J Anesth. 2012;109(6):843-50.
21] Wlodzimirow KA, et al. A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients. Critical Care.
012;16:R200.
22] Gould CV, et al. Guideline for Prevention of Catheter-Associated Urinary Tract Infections. HICPAC. 2009.
Kidney
Stress
Decreased Function
Asymptomat
ic
Symptomatic (Diagnosis)
Serum Creatinine
• Lagging indicator20
• Only elevates after 50%
kidney function lost20
• Non-diagnostic for up t
52% of moderate and
severe AKI21
Urine Output
• Lagging indicator21
• Tedious to measure21
• Affected by HAI
initiatives22
ouldn’t it be nice to identify
idney Stress BEFORE the
dysfunction occurs?
Functional Biomarkers
Serum Creatinine, Urine Output
13. [10] Kashani K, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25.
[11] 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.
340 Biomarkers Evaluated
including NGAL & KIM-1
Discovered in 1,200+ Patients
including sepsis, shock, major
surgery and trauma patients
Urinary [TIMP-2]*[IGFBP-7] stood out as the best-
performing biomarkers to predict development of
moderate or severe AKI within 12 hours10
Candidates identified through hypothesis based on AKI
pathophysiology and evaluated individually and in
combinations of 2-4 biomarkers10
Validated in 500+ Critically Ill
Patients from Intended Use
Population
Patients had diverse ICU admissions (surgery, sepsis,
trauma) and common comorbidities (including CKD,
diabetes, heart disease) 11
Rigorous Discovery & Validation Studies Performed
To Identify Biomarkers Of Early AKI Risk Assessment
14. TIMP-2 and IGFBP7 Outperform Existing Biomarkers
AUC for [TIMP-2]•[IGFBP7] was significantly greater than any existing biomarkers.
15. Tissue Inhibitor of Metalloproteinase-2 (TIMP-2)
Insulin-like Growth Factor Binding Protein-7 (IGFBP-7)
TIMP-2 and IGFBP-7 are:14
Biomarkers of cellular stress in the early phase of tubular cell injury caused by a wid
variety of insults (inflammation, ischemia, oxidative stress, drugs, and toxins)
Involved in G1 cell-cycle arrest that prevent cells from dividing until damage can be
repaired
Both biomarkers appear as “alarm” proteins from other nearby cells
This may help explain why urinary TIMP-2 and IGFBP-7 correspond to risk of AKI.
[12] TIMP-2 figure adapted from: Tuuttila A et al. Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution. J Mol Biol. 1998;284:1133-1140.
[13] IGFBP-7 figure adapted from: ModBase: Database of Comparative Protein Structure Models [accessed 2014 December 10]. Available from: http://modbase.compbio.ucsf.edu/modbase-
cgi/model_details.cgi?queryfile=1418152585_2850&searchmode=default&displaymode=moddetail&referer=yes&snpflag=&.
[14] Gocze I, et al. Urinary Biomarkers TIMP-2 and IGFBP7 Early Predict Acute Kidney Injury After Major Surgery. PLoS ONE. 2015;10(3).
Two Novel Urinary Protein Biomarkers Stood Out As A
“Renal Alarm” System
16. ting Ahead of AKI: Measure Kidney Stress Before Damage Occurs
More complete information = personalized medicine
pportunity to consider kidney-protecting strategies
before it’s too late
Gauges the Risk
Injury before
Damage Occur
• Specific to AKI11
• Fast & Simple: 20 min urine te
• Commercially Available in US
• Peer-reviewed evidence11
• Complementary to HAI and Q
initiatives
• Easy, cost effective to Implem
• Baystate Medical Center
Figure adapted from: [10] Lewington AJP, Certa J, Mehta RL Raising Awareness of Acute Kidney Injury: A Global Perspective of a Silent Killer. Kidney Int. 2013;84(3):457-4
[11] NEPHROCHECK Test Kit Package Insert. PN 300152 Rev E
17. Building An Algorithm Around
NephroCheck: Assessment & Prevention
• When Do I Order the NephroCheck Test?
• Sepsis
• CVI
• Shock
• Logistics
• How Long Does it Take To Get the Results?
• How Complicated is it?
18. • Who to Test
• When to Test
• What Will You Do Different
• Different Treatments Sepsis, Shock, Cardiovascular?
• Reassessment After Intervention
• Trend or Treatment Success
• Value of the Negative Test
Building An Algorithm Around
NephroCheck: Assessment & Prevention
19. Team Members: Will order test based on inclusion
teria
oal: To identify patients at risk of AKI before serum
eatinine increases and take pre-emptive action to
tigate incidence of AKI and decrease acute hemodialysi
olume overload, hyperkalemia, severe acidemia).
4 - 48 hours prior to ICU admission history of
potension, use of vasopressors or nephrotoxic
edications, acute respiratory failure, sepsis,
nd high-risk surgery. ALL CV surgery
Our Plan
20. LINICAL RISK FACTORS FOR AKI ARE COMMON BUT NO
ELIABLE FOR ESTABLISHING THE RISK PROFILE FOR A
NDIVIDUAL PATIENT
dney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1-138.
urugan R et al. Acute Kidney Injury in Non-Severe Pneumonia is Associated with an Increased Immune Response and Lower Survival. Kidney Int. 2010;77:527-535.
chino S et al. Acute Renal Failure in Critically Ill Patients: a Multinational, Multicenter Study. JAMA. 2005;294:813-818.
onco C, Ricci Z. The concept of risk and the value of novel markers of acute kidney injury. Crit Care. 2013;17:117-118.
Patient Risk Factors9
• Dehydration or volume depletion
• Advanced Age
• Female gender
• Black race
• CKD
• Chronic Disease (heart, lung, liver)
• Diabetes Mellitus
• Cancer
• Anemia
Acute Risk Factors9,11,13
• Sepsis
• Pneumonia
• Cardiogenic Shock
• Major Surgery
• Cardiac Surgery
• Nephrotoxic Drugs
• Radiocontrast Agents
• Hypovolemia
21. rly recognition and management of patients at risk is paramount
ce there are no specific therapies to reverse established AKI.9
compared to AMI, AKI does not provide early signs and
mptoms sufficient to guide risk assessment.23
rrent methods for risk assessment are insufficient, placing
bstantial numbers of patients at serious risk of death and
rbidity.9,26
21
A BETTER WAY TO IDENTIFY PATIENTS AT RISK
FOR AKI IS PARAMOUNT
[9] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1-138.
[23] Ronco C, Ricci Z. The Concept of Risk and the Value of Novel Markers of Acute Kidney Injury. Crit Care. 2013;17:117-118.
[26] McCullough PA et al. Diagnosis of acute kidney injury using functional and injury biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol.
2013;182:13-29.
22. NEW TECHNOLOGY, ADVANCE WARNING ENABLES
BETTER OUTCOMES
22
What if we could get ahead of
AKI?
Instead of saying, “wait and
see…”
•Early Warning
•Stratify Patient Risk
•Attention on “At Risk”
patients
•Reduce Process Variation
•Improved Communication
23. Target patients – High risk for AKI such as:
CV surgery
- Shock – septic, cardiogenic, hemorrhagic
- Acute decompensated CHF with cardiogenic shock
- ARDS for P/F ratio <200
- Oliguria – persistent after resuscitation
Exclusion:
- Age < 18 years
- Previous renal transplant
- Known stage 2 or 3 AKI
- ESRD, on acute RRT already, or in imminent need of emergent
acute RRT
24. HE CLINICAL CUTOFF WAS SELECTED TO IDENTIFY TH
AJORITY OF PATIENTS AT RISK FOR MODERATE-
EVERE AKI
*For moderate-severe AKI in the next 12 hours.
The NEPHROCHECK® Test cutoff (AKIRISK® Score > 0.3) was prospectively
selected prior to validation studies to achieve*:
High sensitivity and negative predictive value are important in risk
assessment to ensure that:
• The majority of patients who will develop AKI test positive
• Few patients with a negative test result will be at risk of developing AKI
Study A (408 patients) Study B (126 patients)
High sensitivity 92% 76%
Acceptable specificity 46% 51%
High negative predictive value 96% 88%
24
25. A Quantitative NEPHROCHECK® Test Provides Confidence to
dentify the Majority of Patients at Risk for AKI
High sensitivity and negative predictive value for confidence in identifying the majority of patients at risk for AKI.
Confidence the AKIRISK® Score is not elevated due to common comorbidities such as
CKD, diabetes, surgery, sepsis and trauma.
Confidence the AKIRISK® Score is not elevated due to common comorbidities such as
CKD, diabetes, surgery, sepsis and trauma.
Results from Study A and B are not statistically different (p>0.05)
AKIRISK®Score
26. ecent published literature has discussed the role of the NEPHROCHECK® Test used in
onjunction with clinical judgement and includes recommendations on preferred
dney sparing strategies to help prevent kidney damage.19
Published Recommendations to Help Prevent Kidney Damage
[19] Kellum JA, Chawla LS. Cell-Cycle Arrest and acute kidney injury: the light and dark sides. Nephrol Dial Transplant. 2016;1:16-22.
27. With dynamic measurement of the risk for AKI, there will be the opportunity to initiate timely
nd appropriate preventative therapies and monitoring in the ICU, for those patients who are
dged to be at high risk of AKI.49
s well, less costly interventions are easy and reasonable to implement if risk is identified,
uch as considering:9,19,49
Discontinuing nephrotoxins or changing dosage
Volume status & perfusion pressure
Hemodynamic monitoring
Monitoring frequency of serum creatinine and urine output
Earlier nephrology consult.
Acute Kidney Injury (AKI) is a Significant Opportunity to
mprove Quality of Patient Care
[9] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter, Suppl. 2012; 2:1-138
[19] Kellum JA, Chawla LS. Cell-Cycle Arrest and acute kidney injury: the light and dark sides. Nephrol Dial Transplant. 2016;1:16-22
[49] Bihorac A. Acute Kidney Injury in the Surgical Patient: Recognition and Attribution. Nephron. 2015;131(2):118-22.
29. OW AKI RISK: ≤ 0.3 HIGH AKI RISK: > 0.3
dard of Care – document
ND Foley remove ASAP
- Monitor & document hourly UOP & consider Foley insertion/maintain
Serum BUN, Cr. - Serum BUN, Cr. Q 12
- Urine Na, Cr, Eos x 1
- Consider repeat NephroCheck in 12hrs
V/SVI not monitored - Mandatory hemodynamic monitoring for CI/SVV/SVI Q8 POP algorithm
- Check IVC compressibility with US
- Goals -- MAP>70, SVV < 13, CI >2.0
- Vasopressors (phenylephrine, nor-epinephrine, vasopressin)
- Inotrope support (dobutamine or milrinone)
- Low threshold for inotropes if CI < 2, ScvO2 < 70, and/or Lactic Acid increasin
despite adequate MAP and volume expansion
tics or fluids as needed
on physiology
- Diuretics and fluids to be utilized ONLY after determining fluid status POP
- For oliguria or hypotension, IVV expansion SV optimization POP
- Crystalloid, blood products rarely albumin, clinical decision
U Interventions – AKI Bundle Based on NephroCheck AKI Risk
ore
30. OW AKI RISK: ≤ 0.3 HIGH AKI RISK: > 0.3
at NephroCheck if new
(Same incl/excl criteria)
- Consider repeat NephroCheck testing at 12 hr intervals if there is a need to
reevaluate renal stress/intervention
- Avoid & resolve hypervolemia (> 10% fluid gain)
address hemodynamics using physiology POP
use ACEI/ARB
ous use of NSAIDs
- No NSAIDS or ACEi/ARB
- Avoid all unnecessary IV IODINATED contrast dye studies
- Minimize exposure to nephrotoxins (i.e. vancomycin, piperacillin/tazobactam
aminoglycosides)
- ADJUST MEDICATION DOSING ANTICIPATING DECREASED GFR ESPECIALLY IF
REMAINS LOW
U Interventions – AKI Bundle Based on NephroCheck AKI Risk
ore
der RRT/CRRT Initiation: Inadequate UOP > 12-24 hrs, symptomatic volume
ad, metabolic acidemia (or metabolic complicating respiratory acidosis) with pH
Acute hyperkalemia, symptomatic uremia
31. tient History:
1 yo Male with DM, CAD-stent, Afib, COPD
– Creatinine 1.0
– MICU With Active GI Bleed
– Intubated, Central IV Access, A-line Placed
– Bedside UGI Endoscopy For Active Bleed—Vessel Cauterized
– Rebleed > IR for Embolization
Day 1
– Fluid Resuscitation Initial NC 0.31 (high risk AKI)
– BP 70/30, CI 1.5 / SVV 20 (Fluid Responsive)
– 7 Units RBC’s and 8 Liters Crystalloid
nical Status:
he physician managing the patient realized an early bump in NC required
xtremely aggressive fluid resuscitation, especially with such high blood loss.
Concern was “over-resuscitation” of fluid.
e Story: Presented to ED With Syncope, Black Stools x 30 hours
32. nical Issue:
ephroCheck® Test Interpretation: Elevated AKIRisk® Score (> 0.3) Indicates High
sk for Mod/Sev AKI
– AKIRisk Score 0.31 (high kidney stress)
sessment & Intervention:
ter Successful Resuscitation and Embolization
• CI 2.4 / SVV 10
ay 2
• CI 2.2 / SVV 11
Max Creatinine Over Extended Stay
• Creatinine 1.1 Max With NO AKI
ient Outcome:
atient Completely Recovered with no Kidney Damage
e Story: Presented to ED With Syncopy, Black Stools x 30 hours
33. tient History:
4 yo Female with Hx of Sjogrens Disease and Arterio-Venous Malformations
hroughout Bowel
• 95Kg pt Admitted to ED With Hgb 7.6 With GI Bleed/Pain
nical Status:
Day 1--Admitted to MICU
• Hgb Fell to 6, BP 60/40, Unresponsive, Shock
• Intubated and Resuscitated Aggressively with 2 pRBC’s, Fluid and Pressors
• Taken to Interventional Radiology for Embolization
e Story: Shock
34. nical Issue:
ephroCheck® Test Interpretation: Elevated AKIRisk® Score (> 0.3)
dicates higher risk for mod/sev AKI
– AKIRisk Score 0.04 (low kidney stress)
sessment & Intervention:
ay 2: Successful Resuscitation
• Extubated
• Creatinine 1.2, Hgb 9.5
Transferred to Floor on Day 3
urprised to Learn of Low Renal Stress but This Gave Confidence to
uickly Move pt on to Lower Level of Care: Throughput!
y Take Away – Value of Negative Score
e Story: Shock
35. Conclusions: Real Time in the MICU With Sepsis
• When we test with NephroCheck: As soon sepsis is suspected
• Nurse Alerts
• Hospitalist Training
• Why we test: AKI shows up with Sepsis more than any other reported DRG
• Real Time Picture of the Kidneys
• Did Interventions Make a Difference
• Positive Predictive of the Negative Test
• Helps with Family Discussion of Care Plan
• What we do with the results: Including kidney care in sepsis treatment
• Maintain MAP
• Volume Status
• Review Medications
• Remove Nephrotoxins (including Contrast)
36. Advice For Implementing At Your Hospital
Build A Team
Lab, Nephrology, CT Surgeon, Nursing, Administration
Education
Before Implementation
After Adoption
Feedback To the Team Of Success!!!
Make Changes To The Plan As Needed
