Approach to Acute Kidney Injury

Anna Jin, M.D.

LBVA/UCI
7/21/2014

Learning Objectives
Definitions and classification of AKI
Epidemiology and clinical outcome
Diagnosis and etiology
Approach and management of AKI
Risk factors and preventive
strategies

Definition of AKI
a sudden, sustained, and usually
reversible decrease in the glomerular
filtration rate (GFR) occurring over a
period of hours to days.

> 30 definitions used in published

studies

KDIGO Definition of AKI ( 2012 )

Defined by any of the following:
Increase in SCr by 0.3 mg/dL within 48 hours
Increase in Scr by 1.5 times baseline, which
is known or presumed to have occurred within the
prior seven days
Urine volume <0.5 mL/kg/h for six hours

KDIGO Classification of AKI ( 2012 )

Stage

Serum creatinine

Urine output

1.5-1.9 baseline
OR
>0.3 mg/dL

<0.5 ml/kg/hr for 6-12 hrs

<0.5 ml/kg/hr > 12 hrs

2

2-2.9 baseline

3 times baseline
OR
increase in Cr to 4.0 mg/dL
OR
Initiation of RRT

<0.3 ml/kg/hr > 24 hrs

OR
Anuria > 12 hrs

KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012

Definitions of Terminology
Azotemia - the accumulation of
nitrogenous wastes (high BUN)
Uremia clinical manifestation
(symptomatic renal failure)
Oliguria UOP < 400-500 mL/24 hours
Anuria

UOP < 100 mL/24 hours

Epidemiology
5-10% in hospitalized pts
70% in critically ill pts
5-6% ICU pts require RRT
Once AKI occurred, the treatment is
supportive, at an annual cost $10
billion in the US.

Incidence of Non-Dialysis AKI

Kidney Int 2007

Incidence of Dialysis-Requiring AKI

Kidney Int 2007

In-Hospital Mortality Rate 1992-2001

33% -

AKI requiring dialysis

27.5% - AKI not requiring dialysis

4.6% -

no AKI

JASN 17:1135-1142, 2006

AKI and Mortality

Brigham and Womens, 9210 adults Multivariable Odds Ratio for Death

AKI ( in SCr >0.5)

Age (per 10 yr)
CKD
CV dis.
Respiratory dis
GI dis.
Cancer
Infection

6.5
1.7
2.5
1.5
3
2.4
2.9
7.5

<0.0001
<0.0001
<0.0001
<0.04
<0.0001
<0.001
<0.0001
<0.0001

Chertow et al, JASN 16:3365-70; 2005

Increase in Serum Creatinine from Baseline

Chertow GM et al. J Am Soc Nephrol 2005;16:3365

90 Day Mortality Rate in 2001

44.8% - AKI requiring dialysis

40.3% - AKI not requiring dialysis
12.1% - no AKI

JASN 17:1135-1142, 2006

N=634

Lai CF et al. Crit Care 2012

Acute kidney injury increases risk of ESRD among elderly

N= 233.803

Ishani A et al. J Am Soc Nephrol 2009

Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.
Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.
Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

Etiology of AKI
ATN is the cause
in more than 90%.
Sepsis is the leading
cause of ATN

To function properly
kidneys require:
Normal renal blood flow
Prerenal d/t renal hypoperfusion

Functioning glomeruli and tubules

Renal (Intrinsic)

Clear urinary outflow tract for drainage and

elimination of formed urine
Post renal obstruction

Classification of the Etiologies of AKI

Acute
Renal
Injury

Prerenal
AKI

Acute
Tubular
Necrosis

Intrinsic
AKI

Acute
Interstitial
Nephritis

Acute
GN

Postrenal
AKI

Acute
Vascular
Syndromes

Intratubular
Obstruction

Prerenal AKI
Intravascular volume depletion:
-bleeding, GI loss, Renal loss, Skin loss (burn), Third space
loss, poor oral intake (NPO, AMS, anorexia)

Decreased effective circulating volume:

-congestive heart failure, cirrhosis, nephrotic syndrome,
sepsis

Decreased flow through renal artery:

-RAS or occlusion (compartment syndrome), hepatorenal
syndrome, hypercalcemia
-pharmacologic impairment (RAAS blocker, NSAIDs, CNI)

Prerenal Azotemia Tx
In early stages can be rapidly corrected by
aggressive normalization of effective arterial
volume.
Correction of volume deficits
Optimization of cardiac function
Discontinuation of antagonizing medications
NSAIDs/COX-2 inhibitors
Diuretics
RAAS blockers

Renal / Intrinsic AKI

Tubule: ATN (sepsis, ischemic, toxins)
Interstitium: AIN (Drug, infection, neoplasm)
Glomerulus:

AGN (primary, post-infectious,

rheumatologic, vasculitis, HUS/TTP )

Vasculature:
Atheroembolic dz, renal artery thromboembolism, renal artery
dissection, renal vein thrombosis

Intratubular Obstruction
myoglobin, hemoglobin, myeloma light chains,
uric acid, tumor lysis, drugs (bactrim, indinavir,
acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

Acute Tubular Necrosis (ATN)

Sepsis (48%)
Ischemia (32%)
prolonged prerenal
azotemia
Hypotension
hypovolemic shock
cardiopulmonary arrest
cardiopulmonary bypass

Direct toxic Injury (20%)

Exogenous
Radiocontrast
Aminoglycosides
Vancomycin
Amphotericin B
Cisplatin
Acyclovir
Calcineurin inhibitors
HIV meds (tenofovir)
Endogenous (pigment
nephropathy)
Rhabdomyolysis
Hemolysis

Laboratory Findings in Acute Kidney Injury

Index
BUN/PCr Ratio

Prerenal
Azotemia

Oliguric AKI
(ATN)

>20:1

10-15:1

Urine sodium (UNa),

meq/L

<20

>40

Urine osmolality,
mosmol/L H2O

>500

<400

-Fractional excretion
of sodium
-FEUrea

<1%

>2%

Response to volume

<35%
Cr improves with IVF

>35%
Cr wont improve much

Urinary Sediment

Bland, Hyaline

Muddy brown granular

casts, cellular debris,
tubular epithelial cells

Pitfalls: Fractional Excretion of Na

Pre-existing CKD: FeNa 2-3 even without tubular

injury
Poor sensitivity with diuretics use
Picture might be muddied by fluid therapy
Etiologies of FeNa < 1%
hepatorenal syndrome
contrast nephropathy
rhabdomyolysis
acute glomerulonephritis
early obstructive uropathy

Postrenal AKI: Classification

Level of obstruction
Upper tract (ureters)
Lower tract (bladder outlet or urethra)
Degree of obstruction
Partial vs. Complete
Type
Anatomic lesion (unilateral vs. bilateral)
Functional
Duration (Acute vs Chronic)
Cause (Congenital vs Acquired)

Etiologies: Upper tract obstruction

Intrinsic:
Extrinsic:
Nephrolithiasis
Retroperitoneal or
Blood clot
pelvic malignancy
Papillary
Endometriosis/Prolaps
necrosis
ed uterus
Cancer

Abdominal aortic
aneurysm or Iliac
artery aneurysm
Retroperitoneal
fibrosis

Etiologies: Lower tract obstruction

BPH or prostate cancer
Bladder cancer
Urethral strictures
Bladder stones
Blood clots
Functional obstruction as a result of
neurogenic bladder

Postrenal AKI tx
Prompt recognition and relief of obstruction can
prevent the development of permanent structural
damage.
Lower tract obstruction (bladder catheter)
Upper tract obstruction
ureteral stents
percutaneous nephrostomies
Monitor for post-obstructive diuresis
Recovery of renal function dependent upon
duration of obstruction.

How do we assess a pt with AKI?

Is this acute or chronic renal failure?
Establish baseline Cr and assess Cr trend
History and examination
Small kidneys on ultrasound (except for in
-Diabetes, PCKD, Urinary Tract
Obstruction)

Hilton et al, BMJ 2006;333;786-790

AKI: Focused History

Prenal hx: N/V/D? Oral intake? Diuretics?
heart dz, liver dz, previous renal dz?

Hx of

Post-renal sxs: hesitancy, frequency, urgency, weak stream,

dribbling, feeling of incomplete bladder emptying, flank pain.
h/o kidney stones or BPH? Spinal cord injury? Anticholingergic
meds?
Any recent illnesses? Fever? Rashes?
Any recent surgery?
Cardiovascular instability?
Toxin exposure: new medications (Abx, NSAIDs)? IV contrast?
Change in urination, any edema/SOB/Wt. gain?

Look for temporal link of exposure or risk

factor to elevation of Cr or decline in UOP

How to assess volume?

History (intake, fluid loss, meds)
Postural blood pressure and pulse
Daily weights
Ins/Outs, fluid balance/fluid challenge
Signs of volume depletion:
-Dry mouth, Increased thirst, Lightheadedness, Muscle
cramps, extremities are cool to the touch, palpitations,
reduced and dark urine, syncope
-PE: Listlessness/AMS/LOC, tachycardic, weak rapid pulse,
hypotensive (orthostatic vitals), tachypnic, increased
Temp, poor capillary refill, decreased skin turgor,
flattened neck veins, little or no urination for several hrs

 U/A, Urine protein/Cr, Urine Eosinophilla

FeNa, FeUrea
CPK, uric acid
Urine microscopy:
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN
Post-void residual (>100-150 ml c/w voiding
dysfunction)
bladder catheterization
renal ultrasound

Management of AKI: general principle

No therapy to date have shown efficacy in

treating AKI.
Identify the etiology and treat the
cause

underlying

Optimization of hemodynamics to increase renal

perfusion
Lack of benefit low dose dopamine, loop
diuretics only if markedly fluid overload
Identify and aggressively treat infection (early
removal of foley catheters, and minimize
indwelling lines)

Management of AKI:
treat complications
Correct fluid imbalances: strict I/Os, daily wts.
determine fluid balance goals daily, fluid selection or
diuresis, readjust for UOP recovery, post diuresis or
dialysis
Electrolyte imbalances (low K/phos diet, binder)
Metabolic acidosis (Bicarb deficit, mode and rate of
replacement)
Nutrition: adjust TPN/protein intake
Medication dosing: adjustment for eGFR to avoid
under or over dosing, timing for dialytic therapy,
reassess dosing for renal recovery or dialysis modality)
Procedural considerations (prefer non-contrast CT,
appropriate to delay contrast exposure, prophylaxis)

Nephrotoxic Drug Exposure

Minimizing nephrotoxin
Avoid Aminoglycosides, Amphotericin,
Bactrim, Vancomycin, NSAIDs, IV
contrast, Fleets enemas
Renal dose medications especially
antibiotics and monitor level
Cautious use (metformin, long acting oral
hypoglycemic agents, insulin, gemfibrozil
and statins, neurotin, colchicine/allopurinol,
morphine/codeine, lmwh)

Ancient Chinese Medical Text

The inferior doctor treats actual
illness.
The mediocre doctor attends to
impending illness.
The superior doctor prevents illness.
2600 BC - Huang Dee Nai-Chang

Be aware of pts who are at risk for AKI

Volume depletion or Hypotension
Sepsis
Pre-existing renal, hepatic, or cardiac dz
Diabetes mellitus
Elderly
Exposure to nephrotoxins
Aminoglycosides, amphotericin,
immunosuppressive agents, chemo.,
NSAIDs,, RAAS blockers, intravenous
contrast media
Post cardiac or vascular Surgery pts or
ICU pts with multiorgan failure

Take Home Messages: AKI

AKI is increasingly common.

It involves high cost of management, carries a high morbidity
and mortality risks.
The most common cause of in-hospital AKI is ATN that results
from multiple acute insults (sepsis, ischemia, or nephrotoxin).
No drug treatment has been shown to limit the progression of, or
speed up recovery from AKI.
Review medications and adjust dose
Recognize risk factors
The Best Treatment is PREVENTION and avoid further renal
damage!!!

 Examine pt: BP? Dry? Septic (vasodilated)?

Flush foley (sediment can obstruct outflow)
Check I/Os (has he been drinking?)
Give IV BOLUS (250-500cc IVF), see if pt pees in
next 30-60 min
If he pees, then he was dry
If he doesnt pee, then hes either REALLY dry
or in renal failure
Check UA, UCx, urine lytes
Consider Renal U/S if reasonable

THANK YOU!

RIFLE Criteria for AKI (2005)

Definition of AKI based on AKIN

Acute Kidney Injury Network ( 2007 )
Stage

Increase in Serum
Creatinine

Urine Output

1.5-2 times baseline

OR
0.3 mg/dl increase
from baseline

<0.5 ml/kg/h for >6 h

2-3 times baseline

<0.5 ml/kg/h for >12 h

3 times baseline
OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given

<0.3 ml/kg/h for >24 h

OR
Anuria for >12 h

RIFLE

AKIN

2004

2007

LIMITATIONS

STRENGTHS

KDIGO
2012