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
1.5-1.9× baseline
OR
>0.3 mg/dL 
<0.5 ml/kg/hr for 6-12 hrs
2
2-2.9× baseline
3
3 times baseline
OR
increase in Cr to ≥4.0 mg/dL
OR
Initiation of RRT
<0.5 ml/kg/hr > 12 hrs
<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 (Δ 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
80
ATN is the cause
in more than 90%.
Sepsis is the leading
cause of ATN
70
60
50
Outpatient
Inpatient
40
30
20
10
0
Prerenal
Intrarenal
Obstruct
Idiopath
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%
<35%
>35%
Response to volume
Cr improves with IVF
Cr won’t 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?
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/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
In’s/Out’s, 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/O’s, 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, Fleet’s 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 doesn’t pee, then he’s 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
1.5-2 times baseline
OR
0.3 mg/dl increase
from baseline
<0.5 ml/kg/h for >6 h
2
2-3 times baseline
<0.5 ml/kg/h for >12 h
3
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