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Acute Kidney Injury Ali Salim, MD Professor of Surgery Chief, Division of Trauma, Burns, Surgical Critical Care, and Emergency General Surgery

Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

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Page 1: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Ali Salim, MD

Professor of Surgery

Chief, Division of Trauma, Burns, Surgical Critical Care, and Emergency General Surgery

Page 2: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Disclosures

I have nothing to disclose

Page 3: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Incidence

Definition

Causes

Treatment

RRT Controversies

Page 4: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Sudden decline in kidney function

Due to:

Loss in small solute clearance

↓ GFR

Page 5: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Sudden decline in kidney function

Disturbances in :

Fluid

Electrolytes

Acid base balance

Page 6: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Sudden decline in kidney function

Spectrum of disease

Subclinical injury

Complete organ failure

Page 7: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Common in ICU

7% of hospitalized patients

36% to 67% of critically ill patients

Page 8: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 9: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

↑ morbidity

↑ cost

↑ length of stay

↑ mortality

Mortality ↑ proportionately with ↑ severity

50% - 70% in severe AKI requiring RRT

Independent risk factor for in-hosp mortality

Page 10: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

↑ development of chronic kidney disease

Page 11: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Definitions

Page 12: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Definitions

RIFLE

AKIN

KDIGO

Page 13: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

RIFLE

R -risk

I - injury

F - failure

L – loss

E – end stage kidney disease

Uses serum creatinine and UOP

Page 14: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

RIFLE SCr Criteria UOP Criteria

R ↑ SCr x 1.5 < 0.5 ml/kg/hr x 6

hrs

I ↑ SCr x 2 < 0.5 ml/kg/hr x 12

hrs

F ↑ SCr x 3, or SCr ≥ 4

w/ an acute rise of at

least 0.5

< 0.5 ml/kg/hr x 24

hrs, or anuria x 12 hrs

L Persistent loss of

kidney function > 4

weeks

E Persistent loss of

kidney function > 3

months

Page 15: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 16: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

AKIN

A - acute

K - kidney

I - injury

N - network

Even very small changes in SCr (≥ 0.3mg/dl)

adversely impact outcome

Page 17: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

AKIN Stage SCr Criteria UOP Criteria

1 ↑ SCr ≥ 0.3 or ↑1.5 to

2 fold from baseline

< 0.5 ml/kg/hr > 8

hrs

2 ↑ SCr > 2 to 3 fold

from baseline

< 0.5 ml/kg/hr > 12

hrs

3 ↑ SCr > 3 fold from

baseline, or SCr ≥ 4

w/ an acute rise of at

least 0.5

< 0.5 ml/kg/hr x 24

hrs, or anuria x 12 hrs

Page 18: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 19: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

KDIGO

K - Kidney

D - disease

I – improving

G - global

O - outcomes

Merging of RIFLE and AKIN

Page 20: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

KDIGO

AKI

SCr ↑ ≥ 0.3 in 48 hours; or

SCr ↑ ≥ 1.5 times baseline within 7 days; or

UOP < 0.5 ml/kg/hr for 6 hours

Page 21: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 22: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 23: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Biomarkers

Replace or complement serum creatinine

Can diagnose AKI earlier

May provide information regarding etiology

Cystatin C is used in some hospitals

Page 24: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 25: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Causes of AKI

Page 26: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Top 5 Causes of AKI

Sepsis – up to 50% of cases

Major surgery

Low cardiac output

Hypovolemia

Medications

Page 27: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Medications

NSAIDS

Antimicrobials

Aminoglycosides

Amphotericin

Penecillins

Acyclovir

Chemotherapeutic agents

Page 28: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Other Causes

Hepatorenal syndrome

Trauma

Cardiopulmonary bypass

Abdominal compartment syndrome

Rhabdomyolysis

Obstructive Uropathy

Radiocontrast dye

Page 29: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 30: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Management of AKI

Optimizing hemodynamics

Maintain renal perfusion

Avoid hyperglycemia

Avoid nephrotoxins

Diuretics for volume overload

Adequate nutrition

RRT

Page 31: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Management of AKI

Optimizing hemodynamics

Maintain renal perfusion

Avoid hyperglycemia

Avoid nephrotoxins

Diuretics for volume overload

Adequate nutrition

RRT

Only treatment option for AKI

Page 32: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Management of AKI

No other supportive measures available

Best therapy is avoidance of further injury

Early intervention appears to be beneficial

Ideal intervention still under debate

Page 33: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Indications for RRT

No current consensus on indications

“Absolute” indications

Severe hyperkalemia

Clinically apparent signs of uremia

Severe acidemia

Volume overload

Page 34: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Renal Replacement Therapy

Choice of modality??

Timing of intervention??

Dose/Intensity of treatment??

Page 35: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Choice of Modality

Continuous versus intermittent

Continuous

SCUF

CVVH

CVVHD

CVVHDF

Page 36: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Choice of Modality

Continuous more closely approximate

normal physiology

Slow correction of metabolic derangements

Slow removal of fluid

Better tolerated in critically ill and

hemodynamically unstable

Data??

Page 37: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 38: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Intensity of Renal Support

Intensive renal support:

No decrease in mortality

Did not improve recovery of kidneys

Did not reduce rate of nonrenal organ failure

Page 39: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Zhang et al Am J Kid Dis 2015;66:322-330

Page 40: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Zhang et al Am J Kid Dis 2015;66:322-330

Page 41: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Zhang et al Am J Kid Dis 2015;66:322-330

Page 42: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Continuous versus Intermittent

No difference in outcome

Choice is influenced by:

Individual site availability

Resources

Cost

Clinician bias

Page 43: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Renal Replacement Therapy

Choice of modality??

Timing of intervention??

Dose/Intensity of treatment??

Page 44: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Timing of RRT

Early intervention seems to be important

When to start when conventional indications

are absent?

How early is early?

Page 45: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2011

Page 46: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2011

Page 47: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Earlier appears to be better

Heterogeneous studies

Definitive recommendation cannot be

made…

2011

Page 48: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2016

Page 49: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

KDIGO stage 2

SCr ≥ 2 times baseline or

UOP < 0.5 ml/kg/hr ≥ 12 hrs

Plasma neutrophil gelatinase-associated

lipocalin > 150

2016

Page 50: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Early – within 8 hours of diagnosis

N=112

Delayed – within 12 hours of stage 3 AKI or

upon an absolute indication

N=119

2016

Page 51: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 52: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Early initiation

↓ mortality (39.3% vs 54.7%, p=0.03)

↑ renal recovery (53.6% vs. 38.7%, p=0.02)

↓ RRT duration (9 days vs. 25 days, p=0.04)

↓ hospital stay (51 days vs. 82 days, p<0.001)

2016

Page 53: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2016

Page 54: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

AKIKI Study

KDIGO stage 3

Mechanical ventilation; or

Catecholamine infusion

Page 55: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

AKIKI Study

Early

Immediately after randomization

Late

If at least one criteria met

Severe hyperkalemia

Metabolic acidosis

Pulmonary edema

BUN > 112

Oliguria > 72 hours

Page 56: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

AKIKI Study

Early

N=311

Within 2 hours after randomization

Late

N=308

Within 57 hours after randomization

Page 57: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 58: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2016

Page 59: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Delayed:

No difference in mortality

Averted need of RRT in many

2016

Page 60: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Timing

Question of timing remains unanswered

Still need definition of “early”

More studies warranted

Page 61: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Renal Replacement Therapy

Choice of modality??

Timing of intervention??

Dose/Intensity of treatment??

Page 62: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Dose/Intensity of Treatment

Intensities range from intensive to less

intensive with respect to CRRT

Can also have variable intensities with

intermittent dialysis

What is best??

Page 63: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals
Page 64: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

No difference in outcome between

intensive renal support and less-intensive

support

Page 65: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

2016

Page 66: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Cochrane Review - 2016

Compared less intense (range 20-25

ml/kg/hr) to more intense (35-48 ml/kg/hr)

No difference:

Mortality

Renal recovery

Postsurgical AKI

High intensity appears to reduce risk of death

Page 67: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals

Acute Kidney Injury

Incidence

Definition

Causes

Treatment

RRT Controversies

Page 68: Acute Kidney Injury - seton.net · 50% - 70% in severe AKI requiring RRT ... Can diagnose AKI earlier May provide information regarding etiology Cystatin C is used in some hospitals