Internal Medicine
Nephrology – Lecture 3: ACUTE KIDNEY INJURY (AKI)
Dr. Cortez
ACUTE KIDNEY INJURY
• Rapid decreased GFR occurring over a period of hours to
days
• Clinically diagnosed by one of the ff:
 Increased BUN only (if pre-renal)
 Increased BUN and Creatinine
 Acute oliguria – urine <400 ml/day
Consequences of AKI
• Retention of nitrogenous waste products
• Expansion of ECF volume (volume overload)
• Disorders on electrolytes (hyperkalemia) and acid-base
balance (metabolic acidosis)
ETIOLOGY of AKI
• Pre-renal = 55%
• Intrinsic renal = 40%
• Post-renal = 5%
Lecture:
• Problem in pre-renal: reduced renal blood flow
• Intrinsic renal –disease in the kidneys & its structures
• Post-renal: no abnormality in blood flow or the kidneys;
(+) obstruction in flow of urine
Causes of PRE-RENAL AKI
CLASSIFICATION OF AKI
Non-oliguric
Urine output > 400 ml/day
Oliguric
Urine output < 400 ml/day
Anuric
Urine output < 100 ml/day
Low urine output reflects:
• More severe initial injury (oliguric and anuric)
• Implication for: volume overload and electrolyte
disturbances
• Prognosis
If there is:
• Reduction in GFR
• Obstruction to urine flow
OLIGURIA → always synonymous with ACUTE RENAL
FAILURE
ADQI Definition of AKI
GFR criteria
UO criteria
Risk
↑ Screa x 1.5 or
GFR ↓ 25%
<0.5 ml/kg/hr x 6 hrs
Injury
↑ Screa x 2 or GFR
↓ 50%
<0.5 ml/kg/hr x 12 hrs
Oliguria (< 500ml/day)
Failure
↑ Screa > 4 mg/dL
Acute rise > 0.5
mg/dL
<0.3 ml/kg/hr x 24 hrs
Anuria observed in 12
hrs
Loss
Persistent ARF = complete loss of kidney
function > 4 weeks
ESKD
End stage kidney disease (Loss of kidney
function > 3months with no recovery of kidney
function)
Note: This shows that AKI can lead to ESKD or CKD. If the
patient is diagnosed with AKI then put on dialysis but with no
apparent recovery in 3 months’ time = ESKD
*ADQI – Acute Dialysis Quality Improvement Initiative
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Figure:
• Hepatorenal syndrome – (+) cirrhosis, peripheral
vasodilation, afferent arteriolar vasoconstriction (reduced
blood flow)
• Cardiorenal syndrome – cardiac failure (depleted
circulating blood volume and cardiac output)
• All l/t reduced or diminished renal blood flow
HEPATORENAL SYNDROME (HRS)
• Diagnostic criteria:
 Cirrhosis with ascites
 Serum creatinine > 1.5 mg/dL
 No improvement in serum creatinine after at least 2 days
of diuretic withdrawal and volume expansion with
albumin
 (-) Shock
 (-) Evidence of parenchymal disease
• 2 Types of HRS
 Type 1 HRS
 Type 2 HRS
Type 1 HRS
Rapid progressive AKI with
doubling of serum creatinine level to
> 2.5 mg/dL in < 2 weeks
Type 2 HRS
Moderate renal dysfunction, serum
creatinine of 1.5 – 25 mg/dL with
steady or slow progressive
course
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ABNORMAL COMPARTMENT SYNDROME
• Can cause AKI in patients with:
 Acute abdominal distention
 Rapidly accumulating ascites
 Abdominal trauma
• Mechanism:
 Renal vein compression
 Constriction of renal artery from sympathetic system
and RAAS activation
 Reduced CO
HYPERVISCOCITY SYNDROME
• Ineffective circulation of blood volume kasi malapot ang dugo
• Seen in:
 Multiple myeloma
 Polycythemia
 Macroglobulinemia
INTRARENAL/INTRINSIC AKI
• Problem within the kidney
• Can be caused by:
 Disease of large renal vessels
 Diseases of renal microvasculature
 Glomerular disease
 Tubulointerstitial disease
 Acute Tubular Necrosis (ATN)
Diseases of large
renal vessels
Renal artery stenosis/ thrombosis
/embolism/obstruction/atherosclerotic
plaque
Diseases of renal
microvasculature
• Vasculitis
• Thrombotic
microangiopathies:
HUS, Malignant HPN, TTP,
Toxemia of pregnancy resulting to
HELLP
Glomerular
disease
• AGN, RPGN
*Injury to glomerulus = lower surface
area for filtration = reduced GFR
ACUTE TUBULAR NECROSIS (ATN)
• Necrosis of the tubules
• Can either be:
 Ischemic ATN – 50%
 Nephrotoxic ATN – 35%
Lecture
• ALL pre-renal causes can lead to ischemic ATN
• If the pre-renal causes is/are not addressed and it
goes on, it will not only cause pre-renal AKI but
also ischemic ATN
• 20-30% of patients do not have morphological evidences of
tubular necrosis
•
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•
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Ischemic ATN
All causes of pre-renal azotemia
Hypoperfusion induces ischemic injury to renal cells
Recovery takes 1 – 2 weeks after normalization of
renal blood flow
Extreme effect of renal hypoperfusion: Complete
Cortical Necrosis (irreversible renal failure)
Pre-renal
AKI
Ischemic
ATN
Bilateral
Complete
Cortical
Necrosis
Nephrotoxic ATN
• Increased incidence in:
✓ Elderly (> 40 y/o)
✓ Preexisting CKD
✓ True or “effective” hypovolemia
✓ Concomitant exposure to other toxins (ex.
nephrotoxic drugs)
Exogenous Nephrotoxins that are common causes of
Acute Intrinsic Azotemia with Acute Tubular Necrosis
Disease of Tubulointerstitium Associated with Acute
Intrinsic Renal Azotemia
Notes: The elderly frequently use NSAIDS → prone to ATN
Usual presentation: Drug-induced allergic interstitial nephritis
• Patient takes the drugs. After a few days, px develops
fever, rashes. Examination of urine shows increased
eosinophils, eosinophiluria & elevation of serum creatinine
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Endogenous Nephrotoxins that cause Acute Intrisic Renal
Azotemia with Acute Tubular Necrosis
URETHRAL OBSTRUCTION
• Phimosis, congenital valves, stricture, tumor
MORPHOLOGY OF AKI
4 cellular fates:
• Cellular death by necrosis (tubular necrosis)
• Cellular death by apoptosis
• Cellular replication and division
• Cells may appear indifferent to stress (sublethal changes)
Disruption of
cell
cytoskeleton
• Myoglobin – released from the muscle when there is muscle
injury (trauma, electrical shock, seizure etc.) → toxic to the
kidney → can l/t renal failure
• Hemoglobin – can be from transfusion reactions, hemolysis
of red blood cells
• Uric Acid – acute uric acid production occurs during cancer
therapy. Chemotherapeutic agents and radiation treatment
kill tumor cells which release uric acid → loads the kidney →
toxic (called Tumor Lysis Syndrome or Acute Uric Acid
Nephropathy)
Flattening of epithelium
Loss of brush border
Loss if focal cell contact
Membrane proteins
redistribution (integrins,
Na+K+ ATPase
Redistribution of
ADHESIN
molecules
Loss of cell
polarity
Disengagement
of cells from
substratum
Cellular
dysfunction
INTRATUBULAR
OBSTRUCTIOB
*Research today aims to decrease the production of the
integrins and adhesins. Even with advances in nephrology,
mataas pa rin ang mortality in patients with AKI, especially if it
develops in an ICU setting.
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
• Extgraureteric: Iatrogenic (ligation during pelvic surgery)
• Periureteric: Hemorrhage, tumor, or fibrosis
Lecture:
• In bilaterally functioning kidneys, a unilateral ureteric
obstruction can still be compensated by the other
functioning ureter, therefore AKI does not develop.
• If only one kidney is functioning and the ureter of the
functioning kidney is obstructed → AKI
BLADDER NECK OBSTRUCTION (common)
• Intraluminal: Stones, blood clots, sloughed papillae
• Intramural: Bladder CA, bladder infection w/ mural edema,
neurogenic drugs (tetracyclic antidepressants, ganglion
blockers)
• Extramural: Prostatic hypertrophy, prostatic carcinoma
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CLINICAL FEATURES OF AKI
Acute oliguria
S/S fluid overload/volume depletion
S/S electrolyte imbalance, acid-base disorders
Changes in sensorium
CLINICAL EVALUATION OF AKI
History:
• Fluid losses and fluid intake (state of hydration)
• Urine volume
• Infection: viral, bacterial, fungal
• Drug/s intake
• Radiologic procedures, surgery
• Symptoms of underlying disease
• Diseases or clinical situation that lead to development of
endogenous toxins
• Renal calculi
• Cardiac disease
Physical examination:
• State of hydration; BP, HR, JVP, mucous membrane, skin
turgor
• Signs of chronic liver disease
• Skin lesions
• Edema
• Abdominal findings: (+) KP, distended UB
• Rectal exam – enlarged prostate can obstruct urine flow
• Muscle tenderness/weakness – common in px with
leptospirosis
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Clinical evaluation of VOLUME STATUS
Volume Depletion
• History: thirst, oliguria/anuria, excessive fluid losses, fluid
balance I & O, daily weights
• Physical exam:
 Dry mucosa
 Poor skin turgor
 Absent axillary sweat
 Reduced JVP
 Postural tachycardia/hypotension
 Supine tachycardia/hypotension
NGAL (Neutrophil gelatinase associated lipocalin)
• Highly upregulated after inflammation and kidney injury
• Can be detected in plasma and urine within 2hrs
URINE CHEMISTRY IN ACUTE KIDNEY INJURY (AKI)
Urine chemistry
Pre-renal
ATN
Urine osmolality Uosm
(mosml/kg)
> 500
< 300
Urine to plasma osmolality
>1.5
<1.1
>8
<3
>1.018
<1.015
Urine sodium (mmol/L)
<10
>40
Fractional sodium excretion
<1
>2
Renal failure index
<1
>1
Urine to plasma urea
Specific gravity
Volume Overload
• History: Orthopnea, PND, weight gain, edema
• Physical exam:
 Pitting edema
 Increased JVP
 Neck vein distention
 Elevated Bp
 Pulmonary crackles
STAGING OF AKI
Lecture:
• In pre-renal, there is volume depletion which is compensated
by Na+ and water reabsorption in the tubules. So, urine is
more concentrated (> 500 mosml/kg) and has high specific
gravity. Urinary Na+ is < 10 kasi naabsorb.
• In ATN there is no more compensation even when there are
signals to reabsorb water (may tubular necrosis na). So,
urine osmolality is low (<300 mosml/kg) and lower specific
gravity. Urine sodium is > 40 kasi di naaabsorb.
Example ((clinically)
• Patient 1: Brought to the ER hypotensive, 80/60 BP, 120 HR
2 days oliguric, defecating and vomiting for 3 days. Serum
creatinine is 6.5. After 4 liters of hydration (NSS or plain LR),
patient is still not urinating.
 This patient may have developed ischemic ATN already
• Patient 2: Defecating and vomiting. After a few hours of
arriving to the ER, patient presents with postural
hypotension, tachycardia, dry skin lesions. Serum creatinine
is 4.5. After only 2 liters of hydration, the patient urinated.
 This may patient may have only developed pre-renal AKI
*These criteria are almost the same as RIFLE criteria
Biomarkers for AKI
KIM-1 Kidney Injury Molecule
• A transmembrane protein expressed in the PTC injured by
ischemia or nephrotoxins
• Can be detected shortly after ischemic or nephrotoxic injury
in the urine
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