Transcript Acute Renal Failure - Isfahan University of Medical Sciences

Background
• Acute Kidney Injury (AKI) is an abrupt loss of renal function
that results in the retention of nitrogenous and other waste
products. This can lead to metabolic and organ
dysfunction.
• Renal function is most easily monitored by measuring the
serum creatinine level and estimating the glomerular
filtration rate (GFR)
What is GFR? How is it Calculated?
• The Glomerular Filtration Rate (GFR) is the
volume of fluid filtered from glomerular
capillaries into the Bowman’s capsule per
unit time
Risk Factors for AKI
• Age > 75 yrs
• Chronic kidney disease (CKD, eGFR < 60
mls/min/1.73m2)
• Cardiac failure
• Diabetes mellitus
• Hypovolemia
• Nephrotoxic medication
• Atherosclerotic peripheral vascular disease
• Liver disease
• Sepsis
Definition of AKI
As per the Acute Kidney Injury Network:
• An abrupt (within 48hrs) reduction in kidney function
defined as an increase in serum creatinine level of
0.3mg/dl
OR
• An increase in serum creatinine ≥ 50%
OR
• Urine output is < 0.5ml/kg/hr for >6 consecutive hours
Etiologies of AKI
• Prerenal- causes that decrease effective blood flow to the
kidneys
o Volume loss (dehydration, bleeding, renal loss, GI loss,
burns, 3rd spacing), decreased cardiac output, systemic
vasodilation, renal artery disease, etc.
Etiologies of AKI
• Intrinsic (Renal)- causes due to damage to the kidney
itself
o Acute tubular necrosis, glomerulonephritis, acute
interstitial nephritis, vasculitides, autoimmunity,
drugs, infection, etc.
Etiologies of AKI
• Postrenal- causes as a result of urinary tract
obstruction, can occur anywhere from the renal
pelvis to the urethra.
o Stone, stricture, tumor, clot, prostate etiology,
bladder neck obstruction, extraluminal
compression, etc.
Baseline Set of Laboratories to Consider
• Biochemistry
o urea and electrolytes
• Hematology
o CBC
• Urinalysis (+/- microscopy, eosinophils)
• Urinary Biochemistry
o electrolytes, urea, osmolality
• Microbiology
o urine/blood culture when/if infection suspected
• Imaging
o renal ultrasound
o CXR, abdominal x-ray
• ECG
Urine Patterns in Renal Disease
Urinary Pattern
Hematuria with red cell casts, heavy
proteinuria, or lipiduria
Renal Disease
Glomerular disease or vasculitis
Granular and epithelial casts with free epithelial Acute Tubular Necrosis
cells
Pyuria with white cell and granular casts and
no/mild proteinuria
Tubular or interstitial disease or obstruction
Hematuria and pyuria with no or variable
casts(excluding red cell casts)
Acute interstitial nephritis, glomerular disease,
vasculitis, obstruction, renal infarction
Pyuria alone
Usually infections, sterile pyuria suggests TB
Management
Importantly, manangement of AKI is varied and depends on
the cause. Given no effective pharmaceutical options,
management of AKI is primarily supportive. However, some
general principles can be applied.
• Prerenal azotemia is usually responsive to isotonic fluid
repletion
• Managament of ATN includes discontinuation of
nephrotoxic agents, optimization of hemodynamics,
continued monitoring of renal function (acid/base status,
electrolyte abnormalities).
• Postrenal causes warrant removal of the obstruction.
Management Cont.
• Things to do for patients with AKI
o Renally dose medications
o Avoid nephrotoxins
o Monitor I/Os
o Serial assessment of serum creatinine
• Renal Replacement Therapy (i.e dialysis) is the central
component of care for patients with severe AKI
• The generally accepted indications for renal replacement
therapy in the setting of AKI include:
o Acidosis
o Electrolyte disturbance
o Ingestion/Intoxication
o Volume Overload
o Overt Uremia
5 Key Steps in Evaluating Acute Renal
Failure
1) Obtain a thorough history and physical;
review the chart in detail
2) Do everything you can to accurately
assess volume status
3) Always order a renal ultrasound
4) Look at the urine
5) Review urinary indices
Acute Renal Failure
Muddy Brown Casts:
Highly suggestive of
ATN.
Pigmented granular
casts as seen in
hyperbilirubinemia can
be confused for these.
UpToDate Images.
Acute Renal Failure
White Blood Cell Casts:
Raises concern for
interstitial nephritis.
Can be seen in other
inflammatory disorders.
Also seen in
pyelonephritis.
UpToDate Images.
Acute Renal Failure
• Hematuria
Nonglomerular hematuria:
Urologic causes.
Bladder/Foley trauma.
Nephrolithiasis.
Urologic malignancy.
May be “crenated” based upon age
of urine, osmolality – NOT
dysmorphic.
Acute Renal Failure
Dysmorphic Red Cells:
Suggestive of glomerular
bleeding as seen with
glomerulonephritis.
Blebs, buds, membrane
loss.
Rarely reported in other
conditions – DM, ATN.
Red Blood Cell Casts:
Essentially diagnostic of
vasculitis or
glomerulonephritis.
Acute Renal Failure
Crystals – Pretty and important.
Uric acid crystals:
Seen in any setting of
elevated uric acid and an
acidic urine.
Seen with tumor lysis
syndrome.
UpToDate Images.
Calcium oxalate crystals:
Monohydrate – dumbell
shaped, may be needle-like.
Dihydrate – envelope shaped.
Form independent of urine pH.
Seen acutely in ethylene glycol
ingestion.
Diagnostic Evaluation of
Renal
Failure
10015%
80Cumulative 60% Correct
Diagnosis 40-
25%
60%
200Hx, PE, Labs
Therapeutic
Trials
Renal
Biopsy
Renal Biopsy-When?
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Exclude pre- and post-renal failure, and
clinical findings are not typical for ATN
Extra-renal manifestations that suggest a
systemic disorder
Heavy proteinuria
RBC casts
Case 1
A 42 year male is admitted to the SICU after sustaining
multiple trauma. His course is complicated by
Enterobacter sepsis with profound hypotension
requiring support with intravenous dopamine. The
urine output has gradually decreased to only 300 ml
per day. The urine sodium is 78.
Ischemic Acute Renal Failure
• A form of ATN often following a prerenal insult
• Severity of renal failure correlates with duration of insult
• Treatment is to optimize renal perfusion, avoid additional
nephrotoxic insults and other supportive measures
Conditions that Lead to Pre-renal Acute Renal Failure
Intravascular Volume Depletion
Decreased Effective Circulating Volume
CHF Cirrhosis Nephrosis
Generalized
or Localized Reduction in
Renal Blood Flow
Hepatorenal
Syndrome
Ischemic
Acute Renal Failure
Sepsis
Phases of Ischemic Epithelial Tubular
Injury
Pre-renal
Initiation
GFR
Extension
Maintenance
Recovery
Time
Risk Factors for Ischemic Tubular Injury
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Volume depletion
Aminoglycosides
Radiocontrast
NSAIDs, Cox-2 inhibitors
Sepsis
Rhabdomyolysis
Preexisting renal disease
HTN
Diabetes mellitus
Age > 50
Cirrhosis
Case 2
A 56 y.o. male presents with complaints of persistent
fever, chills, sore throat, and myalgias for the past 14
days. Ten days ago he started taking amoxicillin he
had on hand for dental prophylaxis. His physical
exam is remarkable for fever to 38.6oC, an exudative
pharyngitis and a diffuse maculopapular rash.
Case 2
Laboratory Data
Result
Normal Range
Serum
Na
134 mEq/L 135-145
K
5.7 mEq/L 3.5-5
Cl
106 mEq/L 100-111
Total CO2
14 mEq/L 24
BUN
46 mg/dL
4-15
Creatinine
3.8 mg/dL 0.6-1.0
Glucose
96 mg/dL
60-100
Whole blood
WBC
12 x109/L
4.5-11.0
Hgb
11 gm/dL
13.5-17.5
Hct
33 %
41.0-53.0
Platelets
216 x109/L
150-440
Urine
Specific gravity
1.010
1.002-1.036
Protein
2+
Negative
Blood
Trace
Negative
Glucose
Negative
Negative
The urine sediment shows 3-5 RBC’s/h.p.f., 20-25 WBC’s/h.p.f., coarse granular and white cell
casts, and rare red cell casts.
Case 2
Acute Interstitial Nephritis-Etiology
• Allergic/Drug induced
• Autoimmune
– Sarcoid
-SLE
– Sjogren’s
• Toxins
– Chinese herb nephropathy
-Heavy metals
– Light chain cast nephropathy
• Infiltrative
– Leukemia
– Lymphoma
• Infections (Legionella, CMV, HIV, Toxoplasma)
Acute Interstitial Nephritis
Clinical Presentation
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Non-oliguric ARF
Fever in allergic and infectious types (except NSAID type)
Rash in allergic type (except NSAID induced)
Eosinophilia
UA: WBC casts
Eosinophiluria (allergic)
Hematuria (NSAID related)
Common Causes of Drug Induced AIN
• NSAIDS
• Antibiotics
– Penicillins
• methacillin
• Ampicillin, amoxacillin, carbenacillin, oxacillin
• Cephalosporins
– Quinolones (ciprofloxacin)
– Anti-tuberculous medications (rifampin, INH, ethambutol)
– Sulfonamides (TMP-SMX, furosemide, thiazides)
• Miscellaneous
– Allopurinol, cimetidine, dilantin
Acute Kidney Injury: AIN causes
DRUGS
INFECTION
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ACEI
Allopurinol
Cephalosporins
Cimetidine
Fluoroquinolones
Loop diuetics
NSAIDS
PCN
Phenytoin
Rifampin
Sulfonamides
Tegretol
Thiazides
Bacterial
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Agents causing pyelonephritis
Legionella
Brucella
Yersinia
Viral
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Hantavirus
HIV
CMV,EBV,HSV
Acute Interstitial Nephritis
Treatment
• Withdrawal of offending agent
• Treatment of underlying process if infectious/autoimmune
etiology
• Trial of corticosteroids, especially in allergic presentations
1 mg/kg/day or 2 mg/kg every other day
– No randomized trials proving efficacy
– Reversal of renal failure usually seen in < 6 weeks
Rhabdomyolysis
• Often develops in the setting of crush injury, especially if
superimposed circulatory shock
• Hallmarks of diagnosis
– CK > 10,000
– (+) dipstick for blood but no RBCs
• Treatment
– Volume expansion (judiciously if severe oliguria or azotemia)
– Fasciotomy when indicated for compartment syndrome
(“second wave phenomenon”)
• Avoid calcium repletion unless neuromuscular manifestations
present
• Rebound hypercalcemia in recovery phase
Aminoglycoside Nephrotoxicity
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Generally presents 1 week after exposure
Non-oliguric
Low trough levels do not guard against nephrotoxicity
Incidence of ATN
– 10% after 1 week
– 40% after 2 weeks
• Risk factors for ATN
– Advanced age
– Liver disease
- Superimposed sepsis
- Hypotension
Radiocontrast-Induced
Acute Renal Failure
• Induces renal vasoconstriction and direct cytotoxicity via
oxygen free radical formation
• Risk factors:
– Renal insufficiency
– Advanced age
– Hypotension
- Diabetes
- > 125 ml contrast
• Usually non-oliguric ARF; irreversible ARF rare
Contrast Induced Nephropathy
• Assess CIN risk
– eGFR <30 – Hospital admission, Nephrology consult, Dialysis planning, renal protection
– eGFR 30-59 – Discontinue NSAIDs, IV volume expansion, Intra-arterial: isoosmolar, Intravenous: iso-osmolar or low osmolar contrast; limit contrast volume
– eGFR >60, Discontinue metformin
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Optimal Volume Status
Low-osmolality contrast media
F/U Creatinine 24 – 72hr after contrast exposure
Adequate IV volume expansion with isotonic crystalloid for 3 – 12hr before
the procedure and continue for 6 – 24hr afterward. Oral fluid data is
insufficient
• No adjunctive medical or mechanical treatment has been proved to be
efficacious
• Prophylactic hemodialysis and hemofiltration not validated
Acute Renal Failure due to
Intratubular Obstruction
• Crystalluria
– Ethylene glycol: Calcium oxalate
– Tumor lysis: Urate and Calcium phosphate
– Medications
• Acyclovir
• Methotrexate
• Sulfonamides
• Anti-retroviral agents
• Myeloma cast nephropathy
Case 3
A 35-year-old Hispanic female presents with a one
month history of periorbital and lower extremity
edema. Over two days prior to presentation she has
experienced arthralgias in her wrists and elbows. On
physical examination she is in no acute distress.
Blood pressure is 162/94, temperature 37.4 . Her
skin exam is significant for a malar erythematous
rash. The heart and lungs are normal. There is 3+
edema to the thighs bilaterally.
Case 3
Laboratory Data
Serum
Na
K
Cl
Total CO2
BUN
Creatinine
Glucose
Anti-neutrophil antibody 1:160
Whole blood
WBC
Hgb
Hct
Platelets
Urine
Specific gravity
Protein
Blood
RBC
Sodium
Creatinine
Result
Normal Range
138 mEq/L
4.2 mEq/L
108 mEq/L
17 mEq/L
75 mg/dL
3.5 mg/dL
83 mg/dL
Negative
135-145
3.5-5
100-111
24
4-15
0.6-1.0
60-100
5.9 x109/L
11.9 gm/dL
34 %
153 x109/L
4.5-11.0
13.5-17.5
41.0-53.0
150-440
1.015
3+
3+
>50/h.p.f.
10 mEq/L
35 mg/dL
1.002-1.036
Negative
Negative
0-4
Variable
Variable
Case 3
AKI: Glomerulonephritis (RPGN)/Systemic
Vasculitis
• Immune-Complex Mediated
• SLE
• Cryoglobulinemic vasculitis
• Henoch-Schönlein purpura
• Pauci-immune vasculitis
• Microscopic polyangiitis
• Wegener’s granulomatosis
• Churg-Strauss syndrome
• Post-strep GN
• Direct Ab attack
• Anti-GBM disease
• Goodpasture’s syndrome
• Thrombotic
Microangiopathy
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TTP
HUS
Scleroderma renal crisis
Preeclampsia
Malignant hypertension
AKI: Summary
• Small changes in creatinine can have grave
clinical consequences
• ABCDE assessment and careful management of
fluid status is mainstay of treatment
• Get help early
Future fixes…
• Neutrophil GelatinaseAssoc. Lipocalin (NGAL)
– Levels in blood and urine rise
within a few hours after
injury
• Cystatin C
– Absorbed by kidney, but not
secreted
– Rises one day before Cr
• Interleukin 18
– Produced by caspase-I which
is implicted in pathogenesis
of ARF
Have been shown to predict AKI severity in post-op
hearts