PREDICTING AKI IS MORE CHALLENGING AS AGE PROGRESSESSandra Kane-Gill, PharmD, MSc

Associate Professor, School of Pharmacy

Co-Investigators• Florentina Sileanu, BS, PhD candidate• Greg Trieteley, PharmD candidate• Ragi Marugan, MD• Steven Handler, MD• John Kellum, MD

Putting the Problem in Context• Acute kidney injury (AKI)

• Develops over hours to days in either community or hospitalized patients

• Incidence of AKI doubled from 2000 to 2009

• Outcomes:• Length of stay 2.4 times longer • Hospital mortality rates as high as 60% in ICU patients and over 80% in patients requiring renal replacement therapies • AKI predisposes patients to progression of chronic kidney disease and end-stage renal disease

• Risk factors:• Advanced age (>65 y.o.)• Organ failure• Sepsis and infection• Cardiac shock• Pre-existing chronic medical conditions• Nephrotoxic drugs• Obesity• Surgery • Transplantation

• Recent rise in AKI contributed to the growing elderly population

Himmerlfarb J. Semin Nephrol 2009;29:658-664.Wang WE et al. Am J Nephrol 2012;35:349-55.Coca SG et al. Nephron Clin Prac 2011;119:suppl 1:c19-24

RESEARCH QUESTIONWill the risk factors or model of prediction be upheld in the elderly population?

Study Design and Sample:Retrospective cohort study from July 2000-June 200845,655

• 7 ICUs with greater than 120 beds

3,762

• Receiving hemodialysis or rental transplant prior to hospitalization

105

• Baseline serum creatinine ≥ 4

1,340

• Underwent liver transplantation prior to hospitalization

494

• Inadequate information to determine AKI status

16• Unknown age

39,938

• Included in analysis

Methods• Data were obtained from the Medical Archival Repository

System (MARS) • International Classification Diseases, 9th edition (ICD9)• Diagnosis related group (DRG) • Severity of illness (APCHE III)• Sepsis (blood culture and antibiotic in 24h of each other)• Hypotensive index• Baseline serum creatinine• Admission creatinine• Reference creatinine

• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) (conventional units)

• eGFR of 75ml/min/1.73m2 when baseline creatinine missing

Methods• Categorized by age (≥ 65 y.o.)

• Cohort evaluated for patients who developed AKI

• AKI classification according to KDIGO

Analysis • Prevalence compared by group and then by year

• Outcome comparison• Mortality • Recovery from renal replacement therapy (RRT)

• 90 and 365 days after first RRT and alive but not in United States Renal Data System

• Risk factor assessment completed using a multivariate logistic regression model • Impact of age• Separate assessment by age group

Results

Stage1 Stage2 Stage30.0%

10.0%

20.0%

30.0%

40.0%

50.0%

4,084(32.2%)

5,476(43.2%)

3,114(24.6%)

3,557(28.6%)

6,020(48.4%)

2,869(23.1%)

AKI Stages by Age Group (p <0.001)

Age < 65 Age ≥ 65

max RIFLE Stage (KDIGO)

Per

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t in

AK

I S

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Results

2000 2001 2002 2003 2004 2005 2006 2007 20080.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

45.0%

50.0%

AKI Stages by Year in Age < 65

no AKI Stage1 Stage2 Stage3

Pe

rce

nt

in A

KI

Sta

ge

wit

hin

Ye

ar

Results

2000 2001 2002 2003 2004 2005 2006 2007 20080.0%

10.0%

20.0%

30.0%

40.0%

50.0%

AKI Stages by Year in Age ≥ 65

no AKI Stage1 Stage2 Stage3

P

erc

en

t in

AK

I S

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Comparison of Outcomes by Age for Patients with Acute Kidney Injury

Multivariable regression analysis of risk factors for AKI patients compared to non-AKI patients

Multivariable regression analysis of risk factors for AKI patients compared to non-AKI patients (≥ 65 and <65)

Age ≥65; N = 15,542; AKI developed on or after Age < 65; N = 19,812; AKI developed on orICU admission; AUC 0.673 after ICU admission; AUC 0.719  

Outcome: AKI OR 95% C.I.for OR p-value OR 95% C.I.for OR p-valueAge < 65 - - - - - - - -Race       .002       <0.001 Black vs. White 1.035 .880 1.218 .675 1.052 .945 1.171 .359 Other vs. White 1.212 1.088 1.349 <0.001 1.255 1.140 1.382 <0.001Diabetes 1.179 1.011 1.374 .035 1.295 1.111 1.509 .001Cardiac Disease 1.192 1.050 1.354 .007 1.590 1.381 1.830 <0.001Surgical 1.072 0.995 1.154 .068 1.117 1.048 1.189 .001Sepsis (24hrs from ICU day 1) 2.549 2.165 2.999 <0.001 2.917 2.601 3.271 <0.001Vasopressors (24hrs from ICU day 1) 1.906 1.716 2.117 <0.001 2.011 1.831 2.209 <0.001Mechanical Ventilation (24hrs from ICU day 1)

2.081 1.927 2.247 <0.001 2.519 2.365 2.682 <0.001

eGFR       <0.001       <0.001 <30 vs >60 2.012 1.542 2.625 <0.001 3.161 2.261 4.420 <0.001 [30-60] vs >60 1.461 1.293 1.651 <0.001 2.530 2.161 2.961 <0.001Hypotensive Index (24hrs from ICU admission)

1.006 1.004 1.008 <0.001 1.010 1.008 1.013 <0.001

History of hypertension 1.075 0.990 1.167 .084 1.469 1.357 1.590 <0.001

Comparison of AUC for Elderly vs Younger

Conclusion• From previous studies, we know age is an independent risk

factor for AKI and this study provides confirmation

• Younger patients are less likely to develop AKI compared to elderly patients, but their in-hospital outcomes are similar, though their prolonged recovery is slightly improved

• Likelihood of developing AKI increases with age; but the ability to predict patients at risk for AKI declines with age using an established set of risk factors

• Automation may assist with identification of patients at risk for AKI, especially considering the current challenges