Transcript Acute Renal Failure for the Intern

Acute Renal Failure for the Intern
Background and Epidemiology
Affects 5%-7% of all hospitalized patients
20%-70% mortality rate overall
ARF in ICU – 50%-70% mortality rate
Mortality rate unchanged over past 50 years
Anatomy 1
 Renal Arteries
 Kidneys
 Glomerulus
 Collecting system
 Ureter
 Bladder
 Urethra
 Renal Vein
Anatomy 2
Glomerulus
PCT
Loop of Henle
DCT
Collecting system
130 to 180 liters is filtered across the
glomerulus every day. 98 to 99 % of
that filtrate is reabsorbed.
Estimations of Renal Function
What do the kidneys do?
Filter the blood
What is the “ideal”
substance to measure?
•Completely filtered
•Not secreted
How can we measure the
function of the kidneys?
Measure the glomeular
filtration of a substance
within the kidneys
•Not reabsorbed / transported
What do we commonly
use to measure renal
function?
Serum Creatinine Concentration
Creatinine
Water soluble breakdown product
of creatine from skeletal muscle
(and ingested meat, suplements).
Creatinine is released into the
circulation at a relatively constant
rate.
Creatinine is freely filtered in the
glomerulus, and is not metabolized
by the kidney.
Remember:
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Not all individuals will
have the same amount of
creatinine in their blood.
Different drugs can affect
the concentration of serum
creatinine (without
affecting a patient’s renal
function).
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Approximately 15% of the urinary
creatinine is secreted in the
proximal tubule (in normally
functioning kidney).
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Cimetidine
Trimethoprim
Decrease Creatinine Secretion 
Rise in serum level by up to 0.5 mg/dl
Effects on Serum Creatinine
Decreased Creatinine Secretion
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Cimetidine >> Ranitidine & Famotidine
Trimethoprim
Interfere with the Assay
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Acetoacetate (Diabetic Ketoacidosis)
Cefoxitin
Flucytosine
Enhanced Creatinine Production
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Large meat meal
Creatine containing supplements
Rhabdomyolysis
Serum Creatinine and Renal Function
Glomerular Filtration Rate
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Cockcroft-Gault Method
Jelliffe Method
MDRD
(140 – age) * weight (kg)
72 * serum Creatinine
(multiply by 0.85 for female)
[98 – 0.8 * (age – 20)] * BSA
186 * sCr ^ (-1.154) * Age ^ (-0.203)
Multiple by 0.743 for female
1.73 * serum Creatinine
(multiply by 0.9 for female)
Multiply by 1.21 for African American
•Assumes albumin = 4.0
95 +/- 20 ml/min in women
•Assumes patient is ~ 1.73 m2
120 +/- 25 ml/min in men
Which formula should you use?
Strengths & Weaknesses
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MDRD
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Underestimates patients with normal
renal function
Overestimates patients with severe
renal impairment.
Cockcroft-Gault
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Underestimates patients at older ages
Overestimates patients at younger ages
All of these formulas are best
used in patient’s with stable
renal function.
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It takes time for the serum
creatinine level to accurately
reflect renal function.
We usually use the
Modification of Diet in Renal
Disease (MDRD) forumula.
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Levey et al. Ann Intern Med.
Mar 1999.
What is Acute Renal Failure?
Increase in sCr > 0.5 mg/dl (44 umol/l)
Increase in sCr > 2-fold
Decrease in GFR > 50%
Decrease in GFR requiring dialysis
Depends on who you talk to!
Classification of ARF
Etiology
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Pre-Renal
Intrinsic Renal
Post-Renal
Urine Output
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Polyuria > 3 liters / day
Oligouria: 400 – 100 cc/day
Anuria: < 100 cc / day
Urinalysis
Intrinsic Renal ARF
usually has an abnormal
urinalysis.
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Are there casts present?
Is there proteinuria
present?
If hematuria is present,
are the RBC’s
dysmorphic?
YOU SHOULD KNOW
HOW TO SPIN A
PATIENT’S URINE!
Urinalysis
Collect 10 – 20 ml of
freshly voided urine in a
sterile specimen container.
Take the sample to the
laboratory.
Centrifuge the specimen
at 2,500 rpm for 5
minutes.
Decant the supernatent.
Place the specimen on a
UA microscope slide.
Urine Microscopy
a
Urine Microscopy, cont.
Renal Tubular Cast
Dysmorphic RBC
Urinalysis Clinical Correlation
Nephritis: “active”
urinary sediment with
casts, RBC’s, WBC’s.
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May be accompanied by
HTN, proteinuria, ARF.
Implies inflammation and
glomerular damage.
Nephrotic Syndrome:
proteinuria without casts.
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Proteinuria (GBM defect)
Edema (low albumin)
Hypoalbuminemia
Lipid Abnormalities
Hypercoagguable State
(AT III depletion)
Pre-Renal ARF
Is the patient dry?
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Etiology
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Aortic dissection
Thromboembolic disease
Drugs (NSAID, ACEI)
Volume Depletion
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Urine Na * Plasma Cr
Acutely reduced renal perfusion
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Bleeding
Third Spacing Fluid
Dehydration
Relative Hypotension
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Shock
Cardiac failure
(Volume depletion)
FENa < 1 %
Plasma Na & Urine Cr
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FEUrea < 35 %
BUN / Cr ratio
Urine Osm and SG
Urine Volume
Heart Rate & BP
Pulse Pressure
Skin Turgor
Mucous Membranes
Thirst
Treatment?
* 100
NSAID’s and ACE-I in the kidneys
ACE-I
NSAID
Inhibit PGmediated
dilatation
inhibit
arteriolar
constriction
Post-Renal ARF
Laboratory Evaluation
Etiology of Obstruction?
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Foley malfunction
Prostatic obstruction
Neurogenic bladder
Post-surgical complication
Retroperitoneal fibrosis / CA
Bilateral Urolithiasis
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FENa – variable
Urine Osm – variable
Radiographic Evaluation
Renal US: hydonephrosis, hydroureter.
Unilateral obstruction often does not cause
rise in serum creatinine (unless patient only
has a single functional kidney).
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Intrinsic Renal ARF
“Active” Urine sediment
implies renal involvement.
Categorized based on
location of injury:
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Tubules
Interstitium
Glomerulus
Vessels
Less common systemic
conditions
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Thadhani, R. et al. N Engl J Med 1996;334:1448-1460
Pre-eclampsia
TTP – HUS
Acute Tubular Necrosis
Most common cause of ARF due
to intra-renal causes (~ 75%)
Urinalysis
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Many causes of ATN
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Transient ischemic episode
Toxic injury to the kidneys
Myoglobinuria (Rhabdomyolysis)
Heavy metals
Contrast exposure
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Iso-osmolar (300 – 400 mOsms)
Urine Na > 20
FENa > 1 %
“Muddy brown casts” are nonspecific,
but sensitive.
Urine Output
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Oligouria: more tubular damage, longer
recovery.
Non-oligouria: less tubular damage,
shorter recovery time.
Still carries a high mortality.
For those who improve
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90% will do so within 3 weeks
99% will do so within 6 weeks
Microscopy of ATN
Tubular Necrosis: Ischemia
Etiology
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Systemic Hypotension
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Cardiogenic Shock
Distributive Shock (sepsis)
Hypovolemia (burns, trauma,
blood loss).
Post-Surgical Anesthesia
Distributive Hypoperfusion
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Thyroid Storm
Heart Failure
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? Hepato-Renal Syndrome
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Tubular cells have a high
metabolism (i.e. are sensitive to
states of low blood flow, hypoxia,
or hypotension).
Continuum with pre-renal
azotemia
Tubular Necrosis: Nephrotoxins
Common Drugs:
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Amphotericin B toxicity is dependent
on the total dose (>3 gram); can also
cause an RTA.
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Aminoglycosides cause proximal
tubule damage resulting in non-oligouric
ATN.
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Cisplatin is directly toxic to the
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tubules; also causes a magnesuria and
hypomagnesemia.
Methotrexate
Radiocontrast
IVIG
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Thadhani, R. et al. N Engl J Med 1996;334:1448-1460
Contrast Induced Nephropathy
Radiocontrast agents
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Osmolality
 First generation contrast
agents had very high
osmolality (1500 – 1800
mosm/kg)
 Second generation contrast
agents have lower osmolality
(600 – 800 msom/kg): iohexol
 Third generation agents have
even lower osmolality (~290
mosm/kg): iodixanol
Ionic versus non-ionic
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First generation were ionic
compounds, newer products
are non-ionic.
Pathogenesis is not fully understood
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Renal vasoconstriction?
Direct toxic effect of contrast?
Tubular injury from oxygen radicals?
Patient’s at highest risk
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Diabetes with renal insufficiency
Baseline CKD (sCr > 1.5 mg/dl)
High total dose of contrast (> 70 cc)
Multiple Myeloma
Hypovolemia (or distributive state)
Concurrent Nephrotoxic Drugs
Contrast Induced Nephropathy
Prevention & Treatment
Prevention:
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Don’t use contrast (MRI?)
Use smallest amounts possible
of non-ionic, low-osmolar
contrast media.
Avoid volume depletion
Avoid NSAID’s
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Sodium Bicarbonate
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D5W + 3 amps NaHCO3/liter (~130 MEQ)
Run at 3.5 cc/kg*hour (ideal body weight)
for 1 hour prior to study, and 1.2
cc/kg*hour for 6 hours after exposure
N-acetylcysteine (Mucomyst)
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600 mg PO BID
Administer 2 doses prior to study, and 2
doses after study.
In Reality…
ATN is commonly
multifactorial –
nephrotoxic drugs
exposed to kidneys
with decreased
perfusion
Thadhani, R. et al. N Engl J Med 1996;334:1448-1460
Interstitial Nephritis
Acute Interstitial Nephritis
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Slight proteinuria
+/- Renal tubular acidosis
+/- Urine Eosinophils
+/- RBC, WBC, and WBC Casts
Caused by allergic reaction to
medication / exposure
Antibiotic AIN
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Classic Triad = fever, rash, eosinophilia.
Presentation is acute
Common Agents
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Chronic Interstitial Nephritis
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Chronic analgesic abuse
Heavy Meatals (lead, cadmium)
Sjogren’s Disease
Chronic Renal Outlet Obstruction
Sickle Cell Anemia
Multiple Myeloma
Beta-Lactams (esp Methicillin)
TMP/SMX
Cephalosporins
Rifampin
FQ
NSAID AIN
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Classic triad often absent
Presentation subacute, or after months
of use of NSAID.
Glomerulonephritis
First determine patient has
glomerulonephritis (not just
nephrotic syndrome).
Low Complement
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Renal Presentation
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Systemic Presentation
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If active sediment
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What are the serum
complement levels?
Does the patient have systemic
symptoms?
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SLE
SBE
Cryoglobulinemia
Normal Complement
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Renal Presentation
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Any of the nephritic syndromes can be
considered an RPGN, if it becomes
rapidly progressive!
PIGN
MPGN
ANCA + RPGN
IgA Nephropathy
Alport’s Syndrome
Systemic Presentation
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Goodpasture’s Syndrome
TTP – HUS
Vasculitis
Wegener’s
PAN
Idiopathic
ANCA
Consultation…
If the patient has
glomerulonephritis,
you should be talking
to nephrology!
Vascular Etiology
Atheroembolic
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Recent intravascular
intervention
Livedo reticularis
Low complement
Eosinophilia
Blue toes
Small Vessel Disease
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Scleroderma
TTP/HUS
DIC
Malignant HTN
Acute Indications for Hemodialysis
AEIOU:
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Acidosis: Which is not responsive to medical therapy
Electrolytes: Hyperkalemia
Toxic Ingestion: Lithium, TCA, Ethylene Glycol, Methanol,
Salicylates, (many others)
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Fluid Overload: Especially in heart failure patients
Symptomatic Uremia: Bleeding, encephalopathy, pericarditis.
What do you need to do as the Intern?
Learn about the patient’s history
 PMHx (CKD, CHF, Cirrhosis).
 Hospital Course
 Recent Surgery?
 Contrast exposures?
 Hypoxic episode?
 Hypotensive episode?
 New drugs?
Is the patient making urine?
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Examine the Patient
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Labs
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Repeat the P2
Check a UA with micro (look at the
microscope slide yourself!)
Estimate proteinuria (spot
protein/creatinine ratio)
Post-obstruction (foley, BPH, atonic
bladder, etc)
Hypovolemia or Pre-renal
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Vital signs
Fluid status (S3, JVD, edema)
Mental Status (uremia?)
Bleeding (uremia? hypovolemia?)
GU Exam +/- Rectal
Bladder scan and/or renal US
What is the patient’s volume status?
Intern Evaluation, cont…
What category of renal failure is present?
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Pre-renal
Intrinsic renal
Post-renal
Is there an indication for acute
hemodialysis?
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AEIOU
What can you do to support the patient?
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Fluid challenge if oligouric / anuric
Remove potential nephrotoxins
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Dose medications for patient’s GFR
Ensure adequate renal perfusion (BP)
Electrolyte management
Fluid management (especially if h/o CHF,
and/or if patient is anuric!)
Remember that ARF is usually
not a disease in itself, but rather
the final common pathway of a
variety of disease states.
Review of ARF
Questions?