Approach to Acute Kidney Injury

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
Learning Objectives

Definitions and classification of AKI

Epidemiology and clinical outcome
Diagnosis and etiology
Approach and management of AKI
Risk factors and preventive
strategies
RIFLE Criteria for AKI (2005)
Definition of AKI based on AKIN
Acute Kidney Injury Network ( 2007 )

Stage Increase in Serum Urine Output

Creatinine
1 1.5-2 times baseline <0.5 ml/kg/h for >6 h
OR
0.3 mg/dl increase
from baseline
2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline <0.3 ml/kg/h for >24 h

OR OR
0.5 mg/dl increase if Anuria for >12 h
baseline>4mg/dl
OR
Any RRT given
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 1.5-1.9 baseline <0.5 ml/kg/hr for 6-12 hrs

OR
>0.3 mg/dL
<0.5 ml/kg/hr > 12 hrs
2 2-2.9 baseline

3 3 times baseline <0.3 ml/kg/hr > 24 hrs

OR OR
increase in Cr to 4.0 mg/dL Anuria > 12 hrs
OR
Initiation of RRT

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
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) 6.5 <0.0001

Age (per 10 yr) 1.7 <0.0001
CKD 2.5 <0.0001
CV dis. 1.5 <0.04
Respiratory dis 3 <0.0001
GI dis. 2.4 <0.001
Cancer 2.9 <0.0001
Infection 7.5 <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

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 Intrinsic Postrenal

AKI AKI AKI

Acute Acute Acute

Acute Intratubular
Tubular Interstitial Vascular
GN Obstruction
Necrosis Nephritis Syndromes
 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, 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%) Direct toxic Injury (20%)

Exogenous
Ischemia (32%) Radiocontrast
prolonged prerenal Aminoglycosides
azotemia Vancomycin
Hypotension Amphotericin B
Cisplatin
hypovolemic shock
Acyclovir
cardiopulmonary arrest Calcineurin inhibitors
cardiopulmonary bypass HIV meds (tenofovir)

Endogenous (pigment
nephropathy)
Rhabdomyolysis
Hemolysis
 Laboratory Findings in Acute Kidney Injury

Index Prerenal Oliguric AKI

Azotemia (ATN)

BUN/PCr Ratio >20:1 10-15:1

Urine sodium (UNa), <20 >40

meq/L
Urine osmolality, >500 <400
mosmol/L H2O
-Fractional excretion <1% >2%
of sodium
-FEUrea <35% >35%
Response to volume Cr improves with IVF 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:
Nephrolithias Retroperitoneal or
is
pelvic malignancy
Blood clot
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: Oral intake? Diuretics?
Hx of heart dz, liver dz, previous renal dz?
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/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 underlying cause
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)
Indications for RRT

Still evolving.Generally accepted

Oliguria/Anuria
Hyperammonemia
Hyperkalemia
Severe acidemia
Severe azotemia
Pulmonary Edema
Uremic complications
Severe electrolyte abnormalities
Drug overdose with a filterable toxin
Anasarca
Rhabdomyolysis
Hemodialysis (HD)

Client selection
Dialysis settings
Works using
passive transfer
of toxins by
diffusion
Anticoagulation
needed, usually
heparin
treatment
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!