ACUTE KIDNEY INJURY

S.P.O. Page 1

ACUTE KIDNEY INJURY
Rapid decrease in GFR occurring over period of
hours to days; reversible damage to renal fxn
In CKD several months to years before devt of
renal dysfunction : progressive; irreversible damage
to renal fxn
Clinically diagnosed by one of the ff:
o Increase in BUN
o Increase in BUN and SCreatinine (SCr
elevation of 50% mpd or 43mg/dl)
o Acute Oliguria UO <400ml/day
No known structural problem on the Asians
AKD Decrease in GFR observed in <3months,
may lead to CKD if remain unreversed in 3 mos
CKD Decrease in GFR observed in >3months
Elevation in nitregenous waste products, BUN,
creatinine, volume overload, electrolyte
Potassium elevation is common hyperkalemia
metabolic acidosis

Overview of AKI, CKD and AKD (interrelationship)

Acute Kidney Injury
Acute Kidney Injury vs. Chronic Kidney Disease
Most cases, the distinguishing features between the 2
is usually straight forward
History
PE
Laboratories

Ultrasound
Small kidneys (<10cm)
Reduction of cortical thickness
Increased echogenecity
Scarring
Multiple cyst
Normochronic, normocytic anemia is seen in CKD
Radiologic changes of renal osteodystrophy are
usually late and seldom helpful in practice
Level of BUN (>140mg/dL) or Serum Creatinine
(>10mg/dL) in patients who appear relatively well
and are still non-oliguric are most likely CKD.
Urinary sediments that is inactive with broad casts
Acute-on-Chronic Kidney Disease
The degree of renal failure has been aggravated by
some intercurrent event
Additional decline in GFR from a superimposed
process as:
o Volume depletion
o Nephrotoxic drugs
o Disease relapse
o Disease acceleration
o Infection
o Obstruction
o Hypercalcemia
o Accelerated hypertension
o Heart failure
Consequence of AKI
Retention of nitrogenous waste products
Expansion of ECF volume
Disorders on electrolytes and Acid-Base balance
ACUTE KIDNEY INJURY no ATN
(ACUTE RENAL FAILURE) old name of AKI;
has ATN; Not all pts with ARF will oliguria
ACUTE TUBULAR NECROSIS not all pt with
AKI has ATN
AKI classified as:
1) NONOLIGURIC
Urine output > 400ml/day (>500
o 40% of patients have this
o Better recovery
2) OLIGURIC almost 60% of patients
Urine output < 400ml/day
o Fluid overload and/or hyperkalemia
o More severe injury
3) ANURIC
Urine output < 100ml/day
ACUTE KIDNEY INJURY

S.P.O. Page 2

Low Urine Output
More severe injury
Implication for volume overload
Electrolyte disturbances
Prognosis
Reduction in GFR
Obstruction to urine flow
Oliguria Acute renal failure
Recent ly, a consensus conference sponsored by t he Acut e Dialysis Qualit y
Improvement Initiative (ADQI) has proposed a new definit ion of ARF, t hat
has been widely endorsed and is increasingly being used. In keeping wit h t he
spect rum of changes seen in AKI, a diagnost ic classificat ion scheme was
developed
ADQI definition of AKI: patient is at
GFR criteria Urine Output criteria
RISK Screa x 1.5
or
GFR >25%
UO <0.5ml/kg/hr x6
hrs
INJURY Screa x 2
or
GFR >50%
UO <0.5ml/kg/hr
x12 hrs.
Oliguria
FAILURE Screa > 4mg/dl
Acute rise >0.5mg/dl
UO <0.3ml/kg/hr
x24 hrs.
Anuria x 12hrs.
LOSS Persistent ARF = Complete loss of kidney
function > 4weeks
ESKD End Stage Kidney Disease
(>3 Months)
*Renal replacement t herapy/t reat ment for t he last t wo (Loss and ESKD)
Tandaan ang UO <30 if t he pat ient is 50 kg

Renal dysfunction is defined in terms of either a rise in creatinine or a
reduction in urine output, the more severe of the two criteria being selected.
RIFLE-F (Failure) is present even if the risk in serum creatinine is less that
the threefold above baseline, provided that the new serum creatinine is
greater than 4mg/dL and has risen by at least 0.5 mg/dL. When the achieved
designation results from ed e.g. RIFLE-Fo. Similarly, a subscript c is used
to denote the presence of preexisting chronic kidney disease.

Features suggesting CKD
1) Symptoms lasting >3months
2) BUN or Creatinine documented months earlier
3) Normocytic, normochromic anemia
a. SCr of 10mg/dl, hgb 80 or .27 hct, azotemia
without obvious blood loss
4) Small bilateral kidneys < 10cm on renal UTZ
(normal on Filipinos: 10 + or 2 SD, so 6 or 7 is
suggestive); in AKI varies
5) Retention of nitrogenous waste products AKI and
CKD have both retention, but CKD: compensated,
AKI uncompensated
6) Expansion of ECF volume late stage(5)
7) Disorders on electrolytes and acid base balance
Etiology of AKI
Pre-renal = 55% blood flow reduction or
hypoperfusion of kidney, most common
Intrinsic Renal = 40% glomerular problem
Post renal = 5% obstruction
GFR is dependent on renal BF, BF is dependent on CO, hence
Decrease in renal blood flow = decrease GFR
Causes of PreRenal AKI

Endot helinafferent const rict or
Endot helin inhibit ors given t o AKI: unopposed NO effect
ACE/ARB dilat es efferent drops GFR
NSAIDs const rict s afferent
HPS product ion of subs t hat causes afferent vasoconst rict ion
Hyperviscosit y Syndrome --. Decreased renal BF
Mult iple myeloma
Polycyt hemia
Macroglobulinema
ACUTE KIDNEY INJURY

S.P.O. Page 3

Prerenal AKI
characterized by renal hypoperfusion
integrity of renal parenchymal tissue is preserved
most common cause of AKI
GFR is corrected rapidly on restoration of renal
perfusion within 24 72 hours = reversible
secondary to disease characterized by
o hypovolemia
o low CO
o systemic vasodilatation
o intrarenal vasoconstriction
associated with bland urinary sediments urine sp.gr
is high, (+)hyaline cast
For Impaired Renal Autoregulation or Compensation






Activation of

Release of




Release of













Intrarenal / Intrinsic AKI
Problem within the kidney
Causes:
o Diseases of large renal vessels
Renal artery stenosis/ thrombosis/
embolism/ obstruction/
atherosclerotic plaque
Operative arterial cross
clamping
Bilateral renal thrombosis /
occlusion
o Diseases of renal microvasculature
Vasculiis wegeners
thrombotic microangiopathies
hemolytic uremic syndrome
malignant hypertension
thrombotic thrombocytopenic
purpura
toxemia of pregnancy
HELLP syndrome, eclampsia
o Glomerular disease
AGN
RPGN
o Tubulointerstitial
Acute Interstitial Nephritis
leptospirosis in Phils





Hypovolemia
1. St ret ch Receptor on ARF
Art eries
Triggers: Afferent
Arteriolar Vasodilation
via local pyogenic reflux
(aut oregulat ion)
2. Synt hesize: A.a.
vasodilat at ion
a. vasodilat ing
prost aglandins
i. PGE2
ii. Prost acyclin
b. Nit ric Oxide
i. Kallikrein
ii. Kinins
Sympat hetic NS
RAS
AVP
Norepinephrine
AVP
Angiot ensin II

1. Vasoconst rict ion
2. Inhibit salt loss t hrough sweat
glands
3. St imulat e salt and H2O
appet it e, rest ore BV and
art erial pressure

Efferent Arteriolar
constriction
preserve
GFR
Act ivat e Barorecept ors
ACUTE KIDNEY INJURY

S.P.O. Page 4

Drug-induced Allergic Interstitial Nephritis
-Lactams
Ampicillin
Amoxicillin
Carbenicillin
Methicillin
Naf cillin
Oxacillin
Pen G
Cephalexin
Cephalotin
Cephradine
Cef otaxime

Other Antibiotics
Ethambutol
p-
Aminosalicy late
Rif ampin
Sulf onamides
Trimetoprim
Ciprof loxacin
Lev of loxacin
Norf loxacin
Vancomy cin

NSAIDS
Aspirin
Celecoxib
Fenoprof en
Ibuprof en
Indomethacin
Mef enamic acid
Naproxen
Phenazone
Pheny lbutazone
Tolmetin

Diuretics
Chlorthalidone
Furosemide
Bumetanide
Thiazides


Other
A-Methly dopa
Allopurinol
Azathioprine
Carbamazepine
Cimetidine
Omeprazole
Clof ibrate
Clozapine
Famotidine
Sulf inpy razone
Phenobarbita
Infectious
Bacterial
Acute
py elonephritis
Leptospirosis
Scarlet f ev er
Ty phoid f ev er
Legionnaires
Dse,
Viral
CMV
Measles
Inf ectious
Mononucleosis
Rocky Mountain
spotted f ev er
Other
Candidiasis
Toxoplasmosis
Miscellaneous
Sy stemic dse.
SLE
Sjogren sy n.
Tubulointerstitial
nephritis and
uv eitis sy n,
Cancer
Ly mphoma
Leukemia
My eloma
Sarcoidosis



Acute Tubular Necrosis (ATN)
Acute Kidney Injury (AKI)
Ischemia (Ischemic ATN) 50%
Nephrotoxins (Nephrotoxic ATN) 35%
20-30% of patients do not have morphological
evidences of tubular necrosis
Ischemic ATN
all causes of prerenal azotemia
hypoprefusion reduce ischemic injury to renal cells
recovery takes in which after normalization of renal
blood flow
Renal Hypoperfusion
Prerenal AKI
Ischemic AKI
Bilateral complete cortical necrosis
Nephrotoxic Injury ATN
Kidney vulnerable to nephrotoxic renal injury
o Rich blood supply 25% of CO
o Ability to concentrate toxins to high level
within medullary interstitium and renal
epithelial cellsc harmful metabolites
o Important site for xenobiotic metabolism
Increase in incidence:
o Elderly > 45 y.o. decrease 0.6 GFR/year
o Preexisting CKD DM Nephropathy
o True or effective hypovolemia
o Concommitant exposure to other toxins

Exogenous Nephrotoxins That are Common Cause of Acute
Intrinsic Azotemia with Acute Tubular Necrosis
Antibiotics
Acyclovir
Cidofovir
Indinavir
Foscarnet
Pentamidine
Aminoglycosides
Amphotericin B
Organic solvents
Ethylene glycol
Toluene
Poisons
Paraquat
Snake bites
Chemotherapeutic agents
Cisplatin
Ifosfomide
Anti-inflammatory and
immunosuppressive agents
NSAIDS (including
COX- 2 inhibitors)
Cyclosporin/tacrolimus
Intravenous immune
globulin
Radiocontrast agents
Bacterial toxin
Contrast mediumIVP
Endogenous
Myoglobin muscle injury
Hemoglobin
Uric acid
Calcium
INH intake(not extrinsic) seizure rhabdomyolysis
Malignancy
hypercalcemia

Causes of Acute Post Renal AKI
Ureteric Obstruction
Intraluminal: Stones blood clot, sloughed renal
papillae, uric acid or sulfonamide crystals, fungus
balls
Intramural: postoperative edema after ureteric
surgery, BK virus-induced ureteric fibrosis in renal
allograft
Extraureteric: Iatrogenic (ligation during pelvic
surgery)
Periureteric: Hemorrhage, tumor, or fibrosis
ACUTE KIDNEY INJURY

S.P.O. Page 5

o 2 functioning kidneys bilateral AKI
o 1 functioning kidney unilateral AKI
Bladder Neck Obstruction
Intraluminal: Stones, blood clots, sloughed papillae
Intramural: bladder CA, bladder infection w/mural
edema, neurogenic, drugs (eg tricyclic
antidepressants, ganglion blockers)
Extramural: Prostatic hypertrophy, prostatic
carcinoma
Urethral Obstruction
Phimosis, congenital valves, stricture, tumor
*Bladder Neck and Urethral Obstruction bilateral
hydronephrosis obstructive nephropathymay lead to
CKD
AKI from obstruction develops:
bladder neck
urethra
bilateral ureteric obstruction
unilateral ureteric obstruction in a pt with one
functioning kidney or with significant preexisting
CKD
Morphology of AKI
4 cellular fates:
Cellular death by necrosis
Cellular death by apoptosis
Cellular replication and division
Cells may appear indifferent to stress
Sublethal Changes walang nakikita even in biopsy





















Integrins prevents cellular dysfunction
Clinical Features:
Oliguria
S/S fluid overload/volume depletion
S/S of underlying causes of ARF
S/S electrolytes imbalance, acid base disorders
Changes in sensorium may be the only
manifestation, early in AKI, Late in CKD

Clinical Evaluati on of AKI:
History:
o Fluid losses and fluid intake
o Urine volume
o Infection: Viral, bacteria, fungal
o Drug/s intake
o Radiologic procedures, Surgery
o Symptoms of underlying disease
o Diseases or clinical situation that leads to
development of endogenous toxins
Renal calculi
Cardiac disease

Physical Examinati on:
State of hydration BP, HR, JVP, mucous
membrane, skin turgor
Signs of chronic liver disease
Skin Lesions
Edema fluid overload
Abdominal findings (+) KP, distended UBobst.
Rectal exam enlarged prostate
Muscle tenderness/weakness
Staging of AKI
Clinical Evaluati on of volume status
Volume depletion:
Hx thirst, oliguria/anuria
Excessive fluid losses
Fluid balance I & O, daily weights
PE dry mucosa, poor skin turgor
Absent axillary sweat
Reduced JVP
Postural tachycardia/hypotension
Supine tachycardia/hypotension
Current status of new urinary biomarkers for discriminating
between different forms of AKI.
Disruption of
cell
cytoskeleton
Fl atteni ng of epi thel i um
Loss of brush border
Loss of focal cel l contact
Di sengagement of cells
from substratum
Membrane protei ns
redi stri buti on
(i ntegri ns, Na-K-
ATPase)
Loss of cel l ul ar pol arity
Cel l ul ar Dysfuncti on
Redi stri buti on of adhesi on
mol ecul es
Intratubul ar obstructi on
ACUTE KIDNEY INJURY

S.P.O. Page 6

Biomarker
name
CPB Contrast
nephropathy
Sepsis or
ICU
setting
Kidney
tx
NGAL 2h
post-
CPB
1-2 days
pre-AKI
2 days
pre-AKI
12-24
hpost-tx
IL-18 6h
post-
CPB
Not
increased
2 days
pre-AKI
12-24
hpost-tx
KIM-1 12h
post-
CPB
Not tested Not tested Not
tested
L-FABP 4h
post-
CPB
1-2 days
pre-AKI
Not tested Not
tested
*The times indicated (in hours) are the earliest time points at which the
biomarker is increased signif icantly f rom baseline values. AKI:acute
kidney injury, CPB:cardiopulmonary bypass, KIM-1 kidney injury
molecule-1;l-FABP; liver-type f atty acid____; NGAL: Neutrophil
gelatinase-associated lipocalin; tx:transplant
Urine Chemistry in Acute Kidney Injury
Urine Chemistry Pre-renal ATN
Urine osmolality, U
osm
(mosm/kg)
>500 <300
Urine to plasma
osmolality
>1.5 <1.1
Urine to plasma urea >8 <3
Specific gravity >1.018 <1.015
Urine sodium (mmol/L) <10 >40
Fractional sodium
excretion
<1 >2
Renal Failure index <1 >1
NGAL and IL-8 detects rise or deflection of GFR in >8hrs better than the SCr; available in the Phils
Urine Sediment in the Differential Diagnosis of Acute
Kidney Injury
Normal or Few RBC or
WBC
Prerenal Azotemia
Arterial thrombosis or
embolism
PreglomerularVasculitis
HUS or TTP
Scleroderma crisis
Postrenal Azotemia

Granular casts
Acute tubule necrosis
(muddy brown)
Glomerulonephritis or
vasculitis
Interstitial nephritis

Red Blood Cell Casts
Glomerulonephritis or
vasculitis
Malignant Hypertension
Rarely interstitial
nephritis
White Blood Cell Casts
Acute intestinal
nephritis or
exudative
glomerulonephritis
Sever
Pyelonephritis
Marked leukemic or
lymphomatous
infiltration
Eosinophils (>5%)
Allergic interstitial
nephritis(antibiotics
NSAIDs)
Athereombolic
Disease
Crystalluria
Acute
uratenephrophaty
Calcium Oxalate
Acyclovir
Indinavir
Sulfonamides
Radiocontrast
Agents

Prerenalwith compensation of decrease renal blood
flowincrease Na and H2O reabsorption in tubules low
urinary Na and H2O concentrationHigh urine
osmolarityHigh urine sp gravitylow urine sodium <10
High SCr, BUN and hyaline cast, High BUN-Crea ratio

ATN no compensation of decrease renal blood
flowdecrease Na and H2O reabsorption in tubules high
urinary Na and H2O concentrationlow urine
osmolaritylow urine sp gravityhigh urine sodium <10
Muddy brown granular cast, low BUN-Crea ratio
*BUN alone can differentiate Prerenal from ATN. N.v. 6:1

BUN and SERUM Creatinine
Rapid elevation (within 24- 48 hrs)
Renal ischemia
Radiocontrast
Atheroembolism
o Elevation later (10-14 days) toxins
o Increase in SK+, Uric acid, PO4
o Decrease in SCa+2
o Metabolic Acidosis -increase AnionGap:
ethylene glycol
methanol toxicity

Laboratory evaluation of AKI
UTZ normal or inc echogenicity,hydronephrosis
X-ray, KUB, IVP, retrogade pyelography ureteral
obstruction (diagnostic and therapeutic)
Ct scan stonogram/ unenhanced helical Ct, CT
angio renal artery stenosis
MRI/MRArenal artery pathology
Doppler UTZ renal artery pathology

Renal Biopsy
If the cause of intrinsic renal failure is unclear
if the cause of glomerular disease is not known
in allergic interstial nephritis
pts on supportive renal replacement for a period of 3
months w/o evidence of recovery
ACUTE KIDNEY INJURY

S.P.O. Page 7

Complications
Volume overload
Electrolyte disorders
Metabolic acidosis
Hyperphosphatemia/ hypocalcemia
Anemia, bleeding time
Uremic syndrome
Infection- common and accounts for 75%of deaths
Cardiac abnormalities: arrhythmia, AMI, pulmonary
embolism
GI bleeding 10 -30% due to stress ulceration on
gastric or small intestinal mucosa
P.S. Read on metabolic acid disorder for next meeting!