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!
