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Acute Kidney Injury
Board Review
AKI
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Basics of AKI
New Biomarkers of renal injury
Pathogenesis of AKI
Treatment of AKI
Clinical questions based learning
Acute Renal Failure
• Acute kidney Injury
• Defined as loss of renal function
,measured by the decline in GFR ,
developing over a period of hours to
days.
• Clinically menifested by the retention of
Nitrogenous products that are normally
excreted by the kidneys
RIFLE Criterion for diagnosis of
AKI
• Acute Dialysis Quality Initiative proposed a
definition for AKI based on stratification of
severity of renal injury.
AKI by AKIN
Usually abrupt increase in s/Cr >0.3 mg or
50% increase in Cr compared to baseline(
usually within 48hrs)
• Decrease in urine output to 0.5ml/kg for 6
hrs
AKIN
• The diagnostic criterion should be applied
only after volume status has been
optimized
• Obstruction needs to be excluded if only
oliguria was used as sole diagnostic
criterion
• Has staging system(1-3)
• Loss and ESRD are removed from AKIN
and used as outcome only.
AKI
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Can be
Oliguric
Non oliguric
Anuric
Clinical expression of the disease is
variable
• Sometimes diagnosed based on blood
tests only.
Incidence of AKI
• Depends upon definition of AKI
• 0.5% if >2mg /dl increase in s/Cr
• 12% if 0.5 mg/dl increase in s/Cr
» Chertow JASN 2006
Markers of AKI
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Serum creatinine
Cystatin C
KIM 1
NGAL
IL-8
Treatment of AKI
• Medical Therapy
• Renal Replacement Therapy
Treatment of AKI
• Pharmacologic therapy of AKI
• Dopamine not recommended either as
prophylaxis or treatment ( Lancet 2000)
esp in critically ill pts as proven in ANZICS
trial where renal dose dopamine was not
associated with any decrease in s/cr or
RRT.
Medical Therapy
• Fenoldopam esp in non diabetics( in comparison
to dopamine may attain better s/Cr, improve
GFR and shorten ICU stay
• Diuretics
• Not recommended based on randomized clinical
trials ( Neph Dial Transplant 1997)
• In comparion of lasix vs dopamine vs placebo, at
48 hrs intervals, no change in s/Cr.
• High dose lasix 2gm/day vs placebo, no effect
on s/Cr and need for RRT
Medical Therapy
• ANP:
• Natriuretic peptides no sustained results
• In randomized control trial looking at 504
pts, primary outcome being at 21 day
dialysis free survival, ANP group had no
statistical difference.
• Insulin like growth factor
Only one clinical trial showing no benefit in
critically ill pts ( Am J Physiology 2000 )
Thyroxine
No benefit in clinically ,may be harmful (KI
2000)
Renal Replacement Therapy
• Timing of RRT initiation
• Indications of RRT
• Prophylactic RRT ( Inten Care Med 1999 )
Modality of RRT
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Modality of RRT
IHD
CRRT
PD
EDD
SLED
Question
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A 77 year-old woman presents with weakness, anorexia, and fatigue for one week. One
month ago, she had symptoms suggestive of a viral infection; at that time the plasma
creatinine concentration was 1.0 mg/dL. She is now admitted because of increasing
symptoms.
Physical examination reveals a blood pressure of 160/100. The remainder of the
examination is noncontributory: there is no edema or rash.
Initial laboratory data include:
BUN = 98 mg/dL
Plasma creatinine = 10 mg/dL
Plasma sodium = 140 meq/L
Plasma potassium = 4.6 meq/L
Hematocrit = 29 percent
Urinalysis = trace protein by dipstick, benign sediment
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A. Is this acute or chronic renal failure? What factors help to make this decision if no prior
history is available?
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B. What categories of renal disease (prerenal, postrenal, glomerular, vascular, or
tubulointerstitial) can cause this type of renal failure with a normal urinalysis?
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C. Is the patient in sodium, water, and potassium balance? How might this be achieved in
the presence of a marked decline in glomerular filtration rate?
Question
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A 74-yr-old man with diabetes, hypertension,chronic kidney disease,
and a baseline serumcreatinine of 1.7 mg/dl undergoes coronary
angiography. Forty-eight hours after the procedure, his serum
creatinine is 1.8 mg/dl. One week later, he is readmitted to the hospital
with abdominal and lower extremity muscle pains. His serum
creatinine is 3.6 mg/dl. His amylase is elevated at 320 U/L, with a
creatinine kinase of 470 U/L. His urine specific gravity is 1.012, with 1
blood and 2 protein by dipstick. Microscopic examination reveals 3 to
5 red blood cells per high powered field, rare white blood cell, and
moderate number of fine granular casts.
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What is the MOST likely etiology of his
ARF?
A. Contrast nephropathy.
B. Atheroembolic disease.
C. Myoglobinuric ARF.
D. Prerenal azotemia.
E. Vasculitis.
Radiocontrast Nephropathy
• Mostly hospital acquried
• Accounts for almost 10% cases of AKI
• Characterized by abrupt decline in renal
function after IV administration of iodinated
contrast material.
• Typically Cr begins to rise within 24-48 hrs
of contrast
CIN
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Risks factors for CIN
CKD
DM
CHF, AMI, PVD ,MM,
Hct
Strategies to prevent RCN
• IV Hydration ( Arch Int Med 2000 )
• Low osmolality contrast medium ( KI 1995
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• Acetylcysteine ( NEJM 2000, NEJM 2006 )
• Sodium Bicarbonate ( JAMA 2004)
• Miscellaneous agents
• Hemodialysis as prophylaxis
Question
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A 43-yr-old woman with end-stage liver disease secondary to hepatitis C
infection is admitted to the hospital with worsening encephalopathy and
ascites. Her serum creatinine on admission is 1.2mg/dl. She is treated with oral
lactulose and neomycin with improvement in her mental status. Her ascites is
treated with large volume paracentesis. Four days into her hospitalization, she
is noted to be oliguric, with a serum creatinine of 3.6 mg/dl. Her BP is 98/60
mmHg, with a heart rate of 96 beats per minute. Jugular venous pulsation is
visible 3 cm above the sternal angle with her head elevated 30°. She is
markedly edematous, and she has a fine petechial rash over her lower
extremities. Her urine sodium is 10mEq/L. Her urinalysis reveals moderate
numbers of bile-stained granular casts.
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Which ONE of the following interventions or diagnostic tests is most important
in differentiating between the potential etiologies of her ARF?
A. Intravenous administration of 50 g of albumin.
B. Intravenous administration of at least 1.5 L of isotonic saline.
C. Measurement of central venous pressure.
D. Renal ultrasound.
E. Assay for serum cryoglobulins.
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Hepatorenal syndrome
• AKI is common in pts with advanced liver
disease.
• Mostly AKI is due to pre-renal ,HRS and
ATN
• Differentiation between these entities may
be difficult.
• Is usually of two types
• Diagnosis is based on the following
criterion
Treatment of HRS
Pharmacologic therapy includes
Vaspressin analogs
60-75%
response
Octreotide with Midodrine not yet
FDA approved for HRS ( Am J of Gas
2005 )
Octreotide , Midodrine with albumin
Definite therapy is Liver
transplantation
RRT is usually not recommended
Question
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A 57-yr-old man is admitted after a motor vehicle accident. He has sustained multiple
fractures and blunt chest and abdominal trauma. His BP is 95/60 mmHg. A left
hemothorax is treated with a chest tube, an abdominal lavage reveals only minimal
blood, and a non-contrasted CT of the abdomen is negative. He is volumeresuscitated with approximately 5 L of crystalloid, and his BP increases to 135/85
mmHg. Twenty-four hours after admission, he is noted to have marked abdominal
distension, his amylase and lipase are elevated, his urine output has decreased to 10
ml/h, and his serum creatinine is 2.3 mg/dl. His central venous pressure is 18 mmHg.
His urine sodium is 12 mEq/L. Urine sediment contains a few fine granular casts. A
renal ultrasound demonstrates a small retroperitoneal hematoma without
hydronephrosis and marked ascites. His intravesical pressure is 27 mmHg.
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Which ONE of the following choices is the
most appropriate next step in the management
of his acute renal failure?
A. Abdominal decompression.
B. Placement of bilateral ureteral stents.
C. Fluid resuscitation.
D. Watchful waiting.
E. Initiation of renal replacement therapy
Abdominal Compartment syndrome
uncommon cause of AKI ( Crit Care 2000)
Seen mostly in trauma pts
Menifested usually as oliguric AKI
Diagnosis requries high index of suspicion
and measurement of intra-vesical pressure
Treatment is decompression of the abdomen
AKI usually resovles with relief of the high
IBP.
Question
• Which ONE of the following choices is not recognized as a risk
factor for the development of aminoglycoside nephrotoxicity?
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A. Volume depletion.
B. Biliary tract disease.
C. Elevated peak drug levels.
D. Elevated trough drug levels.
E. Age 65 yr.
Question
• A 27-yr-old woman with HIV infection treated with highly active antiretroviral therapy (HAART) presents with nausea, vomiting, and
• abdominal and flank pain. Her serum creatinine is 2.8 mg/dl
(baseline value was 0.7 mg/dl 2 wk previously). Urine microscopy is
remarkable for rectangular plate-like and needle shaped crystals.
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Which ONE of the following medications is
most likely to have caused her ARF?
A. Adefovir.
B. Indinavir.
C. Nevirapine.
D. Ritonavir.
E. Zidovudine.
Question
• A 34-yr-old man receiving treatment for HIV infection
presents with severe myalgias. His serum creatinine is
2.1 mg/dl, with a creatine phosphokinase of 7,4000 U/L.
His urinalysis is strongly positive for blood on dipstick,
but he has only 2 to 4 red blood cells per high-powered
field.
• Which ONE of the following medications is MOST
likely to be associated with his ARF?
• A. Acyclovir.
• B. Adefovir.
• C. Cidofovir.
• D. Foscarnet.
• E. Zidovudine.
HIV/AIDS
• Incidence is high in pts with CD4 cell count
<200/mm3 and HIV RNA levels
>10,000/ml and in men ( KI 2005,
prospective cohort study )
• Most common causes are pre-renal and
ATN associated with either opportunistic
infections or drugs
• Rarely TTP/HUS ,Rhabdomyolysis and
AIN
HAART
• Indinavir /Ritonavir usually associated
with crystalluria and development of AKI
.Nephrolithiasis can be seen as well.
• Tenofovir ,Cedoforvir are associated with
Fanconi’s syndrome with severe acid base
disturbances.
Question
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A 23-yr-old Gravida 2, Para 1 woman presents at 32-wk gestation with
increasing lower-extremity swelling. Physical examination reveals the
following: BP 145/95 mmHg, mild right upper quadrant abdominal tenderness
with a gravid uterus, mild hyperreflexia, and marked lower extremity edema
that has developed over the preceding two weeks. Laboratory studies are
remarkable for a hemoglobin of 9.8 g/dl, platelet count of 83,000/mm3,
prothrombin time 13 s, partial thromboplastin time of 41 s, serum creatinine of
1.8 mg/dl, alanine aminotransferase 120 U/L, aspartate amino transferase 92
U/L, bilirubin 3.4 mg/dl, and lactate dehydrogenase of 810 U/L. Urinalysis
shows 3 protein. A peripheral blood smear has moderate schistocytosis.
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Which ONE of the following interventions is MOST appropriate?
A. Immediate delivery.
B. Intravenous methylprednisolone.
C. Intravenous heparin.
D. Plasma exchange.
E. Activated protein C.
Pre-eclampsia
• Usually seen after 20 weeks of gestation
• Usually in very young or older primigravida
• Can be superimposed on pre-existing
Hypertension or renal disease
• Characterized by severe proteinuria, new
onset Hypertension and renal failure
• Can progress to HELLP/Fatty liver of
pregnancy
• Treatment is usually delivery of the baby
Question
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A 42 yrs old male with AML is admitted to the hospital for treatment of AML.
His s/Cr is 0.7mg/dl on admission. He is started on chemotherapy. Pt
becomes nauseous, loses appetite, starts vomiting, and on third hospital
day, he becomes oliguric and repeat chemistries reveal K of 6.4meq/L, Co2
14, Cr of 3.0mg/dl. Calcium is 7.2mg/dl and PO4 is 6.4mg/dl. Pt is started
on IV fluids with normal saline but urine output does not improve. Renal
consult for further work up called.
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The most likely cause of this patient’s AKI is
1 Acute interstitial Nephritis from chemotherapy
2 Hydronephrosis due to prostatic hyperplasia
3 pre-renal AKI
4 Acute Glomerulonephritis
Tumor Lysis Syndrome
• Spontaneous and chemotherapy induced
or radiation induced.
• Characterized by multiple electrolyte
abnormalities.
• Diagonosis is clinical in conjunction with
urine studies.
• Treatment is supportive.
• Prevention is indicated in high tumor
burden conditions.
Question
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A 37-yr-old man with a history of intravenous drug abuse is admitted with a 2-wk history of
fevers and malaise. Blood cultures on admission are positive for coagulase-negative
Staphylococcus, and an echocardiogram demonstratesa vegetation on his aortic valve.
His serum creatinine is 1.1 mg/dl. He is started on antibiotic therapy with vancomycin
and gentamicin, his blood cultures resolve, and he is discharged to home to complete
a 4-wk course of intravenous antibiotics. He is readmitted 2 wk later with recurrent fevers,
having been noncompliant with his outpatient antibiotic regimen. Blood cultures are again
positive for coagulase-negative Staphylococcus. His serum creatinine is now 2.4 mg/dl.
Urinalysis reveals hematuria with some dysmorphic red blood cells but without any casts
noted. Serum complement levels are slightly below the lower limits of normal.
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Which ONE of the following choices provides the most appropriate management
for his acute renal failure?
A. Continue current antibiotic therapy.
B. Discontinue aminoglycoside antibiotic.
C. Discontinue vancomycin.
D. Begin a tapering course of oral prednisone.
E. Begin intravenous methylprednisolone.
Question
• A 23yrs old female is admitted to the
hospital with h/o sore throat. Admission
labs reveal Cr of 2.5mg/dl, proteinuria of
5.6 gms of random quantification. Her
PMH is unremarkable. Last blood test
done three months ago revealed Cr of
0.8mg/dl. Family history is unremarkable.
• What is the most likely cause of her AKI
Contd
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Acute post infectious GN
Hepatitis C related Cryoglobulinemia
Acute Tubular Necrosis
Microscopic Polyangitis
Question
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A 57-yr-old woman with a history of mitral valve prolapse and no history of
renal disease develops Streptococcus viridans endocarditis. She is placed on
intravenous ampicillin and gentamicin. Two weeks into her course of therapy,
she develops worsening shortness of breath and lower extremity edema. On
physical examination, she has an erythematous maculopapular rash across her
legs and lower abdomen. Laboratory studies demonstrate a serum creatinine of
2.6 mg/dl. The leukocyte count is 9800/mm3, with 4% eosinophils. Urinalysis
demonstrates microscopic hematuria and pyuria. The urine stain for
eosinophils is negative.
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Which ONE of the following treatmentoptions would be most appropriate in this
patient?
A. Discontinue gentamicin, continue ampicillin.
B. Discontinue gentamicin and ampicillin, begin vancomycin.
C. Discontinue gentamicin and ampicillin, begin vancomycin and oral
prednisone.
D. Continue current antibiotics without change.
E. Continue current antibiotics and begin intravenous methylprednisolone.
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Contd
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Plasmodium Ovale
Schistosoma Hematobium
Borrelia Burgdoferi
Leptospira Interrogans
Brucella Melitensis
Question
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A 66-yr-old man develops acute renal failure(ARF) following operative repair of
a 5.6-cmabdominal aortic aneurysm. The aneurysm extended superiorly to the
level of the right renal artery and the aorta was cross-clamped above the level
of the right renal artery for approximately10 min. The left kidney was atrophic
with severe atheromatous disease of the renal artery. He developed oliguric
ARF postoperatively. Renal ultrasound1 d postoperative demonstrated a
normal appearing right kidney without evidence hydronephrosis. The patient is
begun on intermittent hemodialysis. On the 8th postoperative day,he notes an
increase in his urine output. Dialysisis discontinued, and his serum creatinine
spontaneously falls from 3.7 mg/dl to 3.4 mg/dl. The following day, however, he
reports no further urine output, and his serum creatinine increasesto 4.1 mg/dl.
Over the next several days, he describes a pattern of fluctuating urine output
with occasional hematuria and has a progressive increase in his serum
creatinine concentration to 6.5 mg/dl
Which diagnostic work-up is MOSTappropriate at this time?
A. Repeat renal ultrasound.
B. Computed tomography (CT) scan of abdomen.
C. Renal biopsy.
D. Abdominal exploration.
E. Resume hemodialysis for unresolved acute
tubular necrosis (ATN).