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 Medi[r]
(1)Biomarkers and Acute Kidney Injury William T McGee MD MHA FCCM
(2)Disclosure
Speakers Bureau:
(3)AKI
Needed a Better Way to Assess AKI
Needed a Better Way to Monitor Kidney Stress In Real Time
Use of ScR and Urine Output is Too Slow and Lagging Increasing Biomarker Presence In Clinical Care
AKI Is Expensive and Has Negative Effect on Metrics and Patients!!
(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
(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%
(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) (Failure)Severe
3% 6% 11% 29% 0% 10% 20% 30%
No AKI Mild (Risk) Moderate
(Injury) (Failure)Severe
Hospital Mortality 90-Day Mortality
In a single-center cohort of 27,841 adult surgical patients undergoing major surgery, it was identified that hospital and 90-day mortality were significantly higher among patients with AKI
(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 TransplantHeart
% of CT S ur ger y w ith A K I Moderate
AKI Severe AKI
Mild AKI No AKI
(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.
Acute Kidney Injury (AKI) is a rapid (typically within about 48 hours) loss of kidney function9 • 96% of AKI does NOT require RRT10
RIFLE/AKIN/KDIGO criteria were validated over the past decade and provide a standardized definition of AKI
The criteria are based on increases and serum creatinine and decreases in urine output and stratify AKI 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)
The criteria are good for epidemiological studies but difficult to apply at the bedside; AKI thus remains largely a clinical diagnosis9
8
(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
2,393 patients admitted to academic hospital ICU in Montreal, Canada from January 2006 through December 2011 KDIGO AKI calculated from SCr values Physician definition of AKI was determined by asking ICU staff if a patient had “acute renal failure”.4
“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 0 100 200 300 400 500
Moderate AKI Severe AKI
Numb
er
of P
atien
ts
(10)Without Better Tools, The Best Doctors Are Challenged With AKI
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%
Although Often Under-reported5, AKI Hits Home:
A Typical 500-Bed Hospital
$16.2 MILLION
COST INCREASE
5,450 DAYS
LENGTH OF STAY
INCREASE
86 PATIENTS
READMISSION INCREASE
ANNUAL ICU IMPACT:
MODERATE/SEVERE AKI
[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 Critical Care Medicine; 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
(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
Asymptomat
ic Symptomatic (Diagnosis)
(12)SUBOPTIMAL DIAGNOSTIC TOOLS MAKE AKI IMPROVEMENT DIFFICULT
12
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.
[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 2012;16:R200.
[22] Gould CV, et al Guideline for Prevention of Catheter-Associated Urinary Tract Infections HICPAC 2009
Kidney
Stress Decreased Function
Asymptom
atic Symptomatic (Diagnosis)
Serum Creatinine
• Lagging indicator20
• Only elevates after 50% of
kidney function lost20
• Non-diagnostic for up to
52% of moderate and
severe AKI21
Urine Output
• Lagging indicator21
• Tedious to measure21
• Affected by HAI
initiatives22
Wouldn’t it be nice to identify Kidney Stress BEFORE the
dysfunction occurs?
(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
(14)TIMP-2 and IGFBP7 Outperform 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
wide 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).
(16)Getting Ahead of AKI: Measure Kidney Stress Before Damage Occurs
More complete information = personalized medicine opportunity to consider kidney-protecting strategies
before it’s too late
Gauges the Risk of Injury before Damage Occurs
• Specific to AKI11
• Fast & Simple: 20 urine test11
• Commercially Available in USA11
• Peer-reviewed evidence11
• Complementary to HAI and QI
initiatives
• Easy, cost effective to Implement • Baystate Medical Center
(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?
(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
(19) Team Members: Will order test based on inclusion
criteria
Goal: To identify patients at risk of AKI before serum
creatinine increases and take pre-emptive action to
mitigate incidence of AKI and decrease acute hemodialysis (volume overload, hyperkalemia, severe acidemia).
24 - 48 hours prior to ICU admission history of hypotension, use of vasopressors or nephrotoxic medications, acute respiratory failure, sepsis,
and high-risk surgery ALL CV surgery
(20)CLINICAL RISK FACTORS FOR AKI ARE COMMON BUT NOT RELIABLE FOR ESTABLISHING THE RISK PROFILE FOR AN
INDIVIDUAL PATIENT
[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
[11] Murugan 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 [13] Uchino S et al Acute Renal Failure in Critically Ill Patients: a Multinational, Multicenter Study JAMA 2005;294:813-818
[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
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
(21)Early recognition and management of patients at risk is paramount
since there are no specific therapies to reverse established AKI.9
As compared to AMI, AKI does not provide early signs and
symptoms sufficient to guide risk assessment.23
Current methods for risk assessment are insufficient, placing substantial numbers of patients at serious risk of death and
morbidity.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
(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
(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 or AKI
(24)THE CLINICAL CUTOFF WAS SELECTED TO IDENTIFY THE
MAJORITY OF PATIENTS AT RISK FOR MODERATE-SEVERE 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%
(25)A Quantitative NEPHROCHECK® Test Provides Confidence to
Identify 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
Results from Study A and B are not statistically different (p>0.05) 25
AK
IR
ISK
® Sc
(26)Recent published literature has discussed the role of the NEPHROCHECK® Test used in
conjunction with clinical judgement and includes recommendations on preferred kidney sparing strategies to help prevent kidney damage.19
Published Recommendations to Help Prevent Kidney Damage
(27)With dynamic measurement of the risk for AKI, there will be the opportunity to initiate timely and appropriate preventative therapies and monitoring in the ICU, for those patients who are
judged to be at high risk of AKI.49
As well, less costly interventions are easy and reasonable to implement if risk is identified,
such 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 Improve 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
(28)(29)LOW AKI RISK: ≤ 0.3 HIGH AKI RISK: > 0.3 - Standard of Care – document
UOP AND Foley remove ASAP
- Monitor & document hourly UOP & consider Foley insertion/maintain - Daily Serum BUN, Cr - Serum BUN, Cr Q 12
- Urine Na, Cr, Eos x
- Consider repeat NephroCheck in 12hrs
- CI/SVV/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 increasing despite adequate MAP and volume expansion
- Diuretics or fluids as needed based 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
(30)LOW AKI RISK: ≤ 0.3 HIGH AKI RISK: > 0.3 - Repeat NephroCheck if new
insult (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
- Can use ACEI/ARB
- Cautious 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 UOP REMAINS LOW
ICU Interventions – AKI Bundle Based on NephroCheck AKI Risk Score
Consider RRT/CRRT Initiation: Inadequate UOP > 12-24 hrs, symptomatic volume
(31)Patient History:
• 61 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
– Fluid Resuscitation Initial NC 0.31 (high risk AKI) – BP 70/30, CI 1.5 / SVV 20 (Fluid Responsive)
– Units RBC’s and Liters Crystalloid
Clinical Status:
• The physician managing the patient realized an early bump in NC
required extremely aggressive fluid resuscitation, especially with such high blood loss Concern was “over-resuscitation” of fluid
(32)Clinical Issue:
ã NephroCheckđ Test Interpretation: Elevated AKIRiskđ Score (> 0.3) Indicates Higher Risk for Mod/Sev AKI
– AKIRisk Score 0.31 (high kidney stress)
Assessment & Intervention:
• After Successful Resuscitation and Embolization • CI 2.4 / SVV 10
• Day
• CI 2.2 / SVV 11
• Max Creatinine Over Extended Stay
• Creatinine 1.1 Max With NO AKI
Patient Outcome:
• Patient Completely Recovered with no Kidney Damage
(33)Patient History:
• 84 yo Female with Hx of Sjogrens Disease and Arterio-Venous Malformations Throughout Bowel
• 95Kg pt Admitted to ED With Hgb 7.6 With GI Bleed/Pain
Clinical Status:
• Day Admitted to MICU
• Hgb Fell to 6, BP 60/40, Unresponsive, Shock
• Intubated and Resuscitated Aggressively with pRBC’s, Fluid and Pressors
• Taken to Interventional Radiology for Embolization
(34)Clinical Issue:
• NephroCheck® Test Interpretation: Elevated AKIRisk® Score (> 0.3) indicates higher risk for mod/sev AKI
– AKIRisk Score 0.04 (low kidney stress)
Assessment & Intervention:
• Day 2: Successful Resuscitation • Extubated
• Creatinine 1.2, Hgb 9.5
• Pt Transferred to Floor on Day
• Surprised to Learn of Low Renal Stress but This Gave Confidence to Quickly Move pt on to Lower Level of Care: Throughput!
Key Take Away – Value of Negative Score
(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 with the results: Including kidney care in sepsis treatment • Maintain MAP
• Volume Status
• Review Medications
(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!!!
: http://www.sccm.org/Communications/Pages/CriticalCareStats.aspx [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=&