Download Acute kidney injury (AKI)

Acute kidney injury
Dr.shahram.sajjadieh.MD
nephrologist
Azotemia
Uremia or Uremic syndrome
ARF (hours to days)
RPRF(days to weeks)
CRF (months to years)
Abrupt decrease of renal function sufficient to result in:
Retention of nitrogenous waste products
 loss of regulation of extracellular volume and electrolytes
Rapid deterioration of renal function


(increase of serum cr of >0.3-0.5 mg/dl in <48-72hrs or a
percentage increase of >50%)

Decreased urine output(<0.5 ml/kg/hr for >6hr)
(usually but not always)
Oliguria: <400 ml urine output in 24 hours
Anuria: <100 ml urine output in 24 hours
ARF
Definition of Acute Kidney Injury (AKI) based on “Acute
Kidney Injury Network”
Stage
Increase in Serum
Creatinine
Urine Output
1
1.5-2 times baseline
OR
0.3 mg/dl increase from
baseline
<0.5 ml/kg/h for >6 h
2
2-3 times baseline
<0.5 ml/kg/h for >12 h
3
3 times baseline
OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given
<0.3 ml/kg/h for >24 h
OR
Anuria for >12 h
Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to
improve outcomes in
Acute Kidney Injury. Critical Care 2007; 11: R31.
Risk of renal injury
Injury to the kidney
Indicator Classes
Failure of kidney function
Loss of kidney function
Outcome Classes
End-stage Kidney Disease
ARF
GFR/Cr criteria
Risk
Injury
Failure
Loss
ESRD
Increase in cr x1.5
Or GFR decrease >25%
Increase in cr x 2
Or GFR decrease >50%
Increase in cr x 3
Or GFR decrease >75%
Urine Output
criteria
UO < 0.5ml/kg/hr
for 6hrs
UO < 0.5ml/kg/hr
for 12hrs
UO < 0.3ml/kg/hr
for 24 hrs or
Anuria for 12hrs
Persistent ARF = complete loss of renal
function > 4 weeks
End Stage Renal Disease > 3 months
ARF
8
Mortality
• Dialysis requiring = 40-90%
• Increased mortality even in patients not requiring dialysis
• 25% increase in creatinine associated with a mortality
rate of 31% compared with 8% for matched patients
without renal failure
Non-Oliguric vs. Oliguric vs. Anuric
• Oliguric renal failure.
– Functionally, urine output less than that required to
maintain solute balance (can’t excrete all solute taken in).
– Defined as urine output < 400ml/24hr.
• Anuric renal failure.
– Defined as urine output < 100ml/24hr.
– Less common – suggests complete obstruction, major
vascular catastrophy, or more commonly severe ATN.
Non-Oliguric vs. Oliguric vs. Anuric
• Classifying by urine output may help establish a
cause.
– Oliguria – more common with obstruction, prerenal
azotemia
– Nonoliguric – intrarenal causes – nephrotoxic ATN, acute
GN, AIN.
• More importantly, assists in prognosis.
– Significantly higher mortality with oliguric renal failure.
– 80% vs. 25% mortality in Oliguric vs. non-oliguric ARF
– Nonoliguric renal failure may also suggest greater liklihood
of recovery of function.
ARF
12



Prerenal Azotemia
55%
Renal
40%
 ATN
90%
(Ischemic , nephrotoxic)
 AIN
 AGN or Vasculitis
 Acute Renovascular Disease
 Microvascular (HUS_TTP, atheroemboli)
Post renal
5%
Admission in wards ~ 5%
Admission in ICU ~ 30%

Chronic Hx of:
 Nocturia,
polyuria, edema or
hematuria
 Pruritus, neuropathy, impotence,
other uremic symptoms
 Underlying predisposing illness
(DM, HTN)

Objective Findings:
Bilateral Small Kidneys
 Renal OsteoDystrophy
 Band keratopathy
 Carbamylated Hemoglobine


Less reliable:
Anemia
 Hypocalcemia
 Hyperphosphatemia

Differentiation between ARF and CRF
Acute
Chronic
Short
(days-weeks)
Long
(month-years)
Hb concentration
Normal
Low
Renal size
Normal
Reduced
ROD
Absent
Present
Peripheral neuropathy
Absent
Present
Serum Cr
Acute reversible
increase
Chronic
irreversible
History
Epidemiology
• Prevalence
– 1-5% all patients admitted to hospital
– 10-30% patients admitted to ICU
• Etiology
– Hemodynamic 30%
– Parenchymal 65%
• Acute tubular necrosis 55%
• Acute glomerulonephritis 5%
• Vasculopathy 3%
• Acute interstitial nephritis 2%
– Obstruction 5%
Clinical Approach to Acute Renal Failure
Acute Renal Failure
Clinical Assessment (Volume Status,
Urinalysis and Ultrasound)
Intra-Renal
Pre-Renal
Absolute Decrease
In ECF Volume
GI losses
Hemorrhage
Decreased
Renal
Blood Flow
Heart failure
Renal artery
stenosis
Altered Intra-Renal
Hemodynsmics
Drug-induced
NSAIDS/COX-2
Inhibitors
Calcineurin inhibitors
ACE inhibitors
AII Receptor Blockers
Sepsis
Hypercalcemia
Cirrhosis/Hepatorenal
syndrome
Abdominal compartment
syndrome
Tubulointerstitial
Disorders
Tubular Injury
Ischemic
Nephrotoxic
Interstitial Nephritis
Allergic-type
NSAID-type
Glomerular Disorders
Glomerulonephritis
Thrombotic
microangiopathies
Atheroembolic
disease
Post-Renal
Anatomic Obstruction
Bladder Outlet
Prostate
Pelvic Tumor
Ureteral
Tumor
Stones
Stricture
Tubular Obstruction
Crystals
Calcium oxalate
(Ethylene glycol
poisoning)
Drugs
Indinovir
Methotrexate
Proteins
Myeloma cast
nephropathy
AKI: Diagnostic studies-urine
• Urinalysis for sediment, casts
• Response to volume repletion with return to baseline
SCr 24-72 hr c/w prerenal event
• Urine Na; FENa
FENa (%) = UNa x SCr x 100
SNa x UCr
– FENa < 1%: Prerenal
– FENa 1-2%: Mixed
– FENa > 2%: ATN
• Hansel’s stain
• BUN/Creatinine ratio.
– > 20:1 – suggest prerenal or obstruction.
– Can be elevated by anything leading to increased urea
production/absorption.
•
•
•
•
GI bleed
TPN
Steroids
Drugs – Tetracycline.
• Creatinine in anephric state typically only rises
1mg/dl/day.
– If greater – should be concerned for rhabdomyolysis
ATN vs. Prerenal Azotemia
Indices
Prerenal
ATN
UNa
< 20
> 40
FeNa
< 1%
> 1%
U/PCreat
> 40
< 20
Confounding Variables in the Diagnosis of Prerenal Azotemia versus ATN
• A low urine Na can also be seen in:
– Contrast induced ATN
– Early ATN or obstruction
– Acute Glomerulonephritis and Nephrotic Syndrome
• Diuretics can elevate the urine Na
• Jaundice may induce “muddy brown” cast formation
Urinalysis in Acute Kidney Injury
Normal/bland
Prerenal
Postrenal
AKI
Abnormal sediment
Hematuria
RBC casts
proteinuria
WBC
WBC casts
Eosinophils
RTE cells
Pigmented
casts
Glomerulopathy
Vasculitis
Thrombotic MA
Pyelonephritis
Interstitial
nephritis
AIN
Atheroembolic
AKI
ATN
Myoglobin
Hemoglobin
Crystalluria
Uric acid
Toxins
Drugs
Nonalbumin
proteinuria
Plasma cell
dyscrasia
Urinary Sediment Findings in
Intra-Renal Acute Renal Failure
Intra-renal Acute
Renal Failure
Tubular proteinuria
Albuminuria
Dysmorphic Hematuria
Red cell casts
Glomerulonephritis
Atheroembolic disease
Thrombotic
microangiopathy
Oval fat bodies
Fatty Casts
Minimal change
disease
Focal segmental
glomerulosclerosis
Muddy brown casts
Renal tubular epithelial
cells and casts
White cells
White cell casts
Eosinophiluria
Tubular epithelial
injury
-Ischemic
-Nephrotoxic
Interstitial nephritis
Urinary tract
infection
Crystalluria
Drug toxicity
Urate crystals
-Urate nephropathy
Calcium oxalate crystals
-ethylene glycol

Symptoms and/or signs of RF:
Weakness and easy fatiguability (from anemia),
 Anorexia
 Vomiting
 Mental status changes or Seizures
 Edema,…


Systemic symptoms and findings:

Fever, arthralgias, pulmonary lesions
ARF
ATAPOUR
Prerenal Azotemia:
- fall in GFR secondary to renal
hypoperfusion that potentially has
rapid reversible component with
restoration of effective intravascular
volume or perfusion pressure.

Pre renal A.
Intermediate
syndrome
ATN
ACN
Postulated
Major
Pathologic
Mechanism
Cortical
hypoperfusion
GFR
Syndrome
(ml/min)
Prerenal 40-100
Azotemia
Medullary
Intermediate 20 - 60
hypoperfusion
syndrome
Medullary
ischemia
ATN
0 - 25
Cortical
ischemia
ACN
0-5
Preventability
Immediate
Within 1–3
days
Within 1–3
weeks
Unpredictable
 Volume depletion
 Renal losses (diuretics, polyuria)
 GI losses (vomiting, diarrhea)
 Cutaneous losses (burns,…)
 Hemorrhage
 Decreased cardiac output
 HF
 Pulmonary embolus
 Acute MI
 Severe valvular heart disease
 Abdominal compartment syndrome
(tense ascites)
ARF
Conditions that Lead to Pre-renal Acute Renal Failure
Intravascular Volume Depletion
Large-vessel Renal Vascular Disease
Decreased Effective Circulating Volume
CHF Cirrhosis Nephrosis
Generalized
or Localized Reduction in
Renal Blood Flow
Medications
CsA, Tacrolimus
ACE inhibitors NSAIDS
Radiocontrast Amphotericin B
Aminoglycosides
Renal Artery Thrombosis
Renal Artery Embolism
Renal Artery Stenosis or Crossclamping
Sepsis
Small-vessel Renal Vascular Disease
Vasculitis Atheroemboli
Thrombotic Microangiopathies
Transplant Rejection
Hepatorenal
Syndrome
Ischemic
Acute Renal Failure
 Most
common cause of intrinsic
cause of ARF
 Often multifactorial
 Ischemic ATN:
 Hypotension, sepsis, prolonged prerenal state
 Nephrotoxic ATN:
 Contrast, Antibiotics, Pigments, heme
protein,…
ARF


Prerenal Azotemia
ATN




Initiation
Extension
Maintenance
Recovery
ARF
Phases of Ischemic Epithelial Tubular
Injury
Pre-renal
Initiation
GFR
Extension
Maintenance
Recovery
Time
1.
Initiation (hours to days)

GFR due to:
 Renal blood flow
 Obstruction of tubules by casts
 Back leak of filterate
ARF
2. Extension:
•
Continued ischemic injury &
inflammation
•
•
•
•
•
Cellular apoptosis/necrosis /sloughing
Disruption of normal epithelial integrity
Abnormal tubular function
Luminal obstruction
Capillary sloughing and worsening
ischemia
ARF
3. Maintenance (1-2 weeks)
 Release of vasoactive mediators from
injured endothelial cells
 Congestion of medullary blood vessels
 Reperfusion injury induced by reactive
oxygen species & inflammatory mediators
release by leukocytes & parenchymal cells
 Tubuloglomerular feedback
ARF
4. Recovery
 Tubular epithelial cell repair and
regeneration
 gradual return of GFR toward
premorbid levels
ARF
Intrarenal
vasoconstrition
ATN
Intratubular
obstruction
Reduction in
Kf
Backleak of
glomerular
filtrate
Diagnostic Index
Prerenal
Azotemia
Intrinsic
Azotemia
>1.018
<1.012
> 500
< 250
BUN / Cr
>20
<10 - 15
Urinary Na conc.(mEq/l)
<10
>20
Fractional Excretion of
Na(%)
UNa×Pcr×100 / PNa×Ucr
Urine sediment
<1
>1
Hyaline casts
Muddy brown
granular casts
Urine SG
Urine Osmolality


Rising RIFLE class associated with
increasing mortality
Patients who are treated with RRT still
have a mortality of 50-60%
ARF
Risk Factors for Ischemic Tubular Injury
•
•
•
•
•
•
•
•
•
•
•
Volume depletion
Aminoglycosides
Radiocontrast
NSAIDs, Cox-2 inhibitors
Sepsis
Rhabdomyolysis
Preexisting renal disease
HTN
Diabetes mellitus
Age > 50
Cirrhosis
ARF

Ureteric obstruction
 Stone, Clot,…
 Ligation during pelvic surgery

Bladder neck obstruction
 BPH
 Neurogenic bladder
 Drugs (TCA, ganglion blockers)
 Stone disease, hemorrhage/clot

Urethral obstruction
 Strictures, Clot,…
ARF



Sepsis accounts for nearly 50% of all
causes of AKI
Combination of Factors
 Immunological
 Toxic
 Inflammatory
Effect renal microvasculature and
Tubular cells
ARF
Definition:
 A group of clinical disorders that
affect principally the renal tubules
and interstitium with relative sparing
of glomeruli and renal vasculature
Classification:
1. AIN
2. CIN
AIN is a clinicopathologic
syndrome of:
ARF
 Associated with interstitial edema
and cellular infiltrate


Etiology
 Idiopathic
 Secondary
10-20% of pts with ARF
who have had a renal
biopsy have AIN

Etiology( Secondary):

Drugs
 Antibiotics, NSAIDs, Allopurinol, Diuretics,…



Systemic infections
 Legionnaires disease,
Strep, CMV,…
Primary Renal Infections
 Acute bacterial pyelonephritis
 Reflux nephropathy
Immune disorders
 SLE, Sjogrens syndrome,…
Leptospirosis,
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
•
•
•
•
•
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)
Lumphocyturia (NSAID related)
Acute Kidney Injury: AIN causes
DRUGS
INFECTION
•
•
•
•
•
•
•
•
•
•
•
•
•
•
ACEI
Allopurinol
Cephalosporins
Cimetidine
Fluoroquinolones
Loop diuetics
NSAIDS
PCN
Phenytoin
Rifampin
Sulfonamides
Tegretol
Thiazides
Bacterial
–
–
–
–
•
Agents causing pyelonephritis
Legionella
Brucella
Yersinia
Viral
–
–
–
Hantavirus
HIV
CMV,EBV,HSV

Drug-induced AIN is secondary to
immune reaction
AIN occurs only in a small percentage of
individuals taking the drug
 AIN is not dose-dependent
 Association with extrarenal manifestations
of hypersensitivity
 Recurrencence after re-exposure

NSAID versus Beta-lactam AIN
Beta-lactam
Duration of exposure
Fever/rash/eosinophilia
Eosinophiluria
> 3 gm proteinuria
Rate of recovery
Chronic renal failure
Benefit of steroids
2 weeks
80%
80%
< 1%
Fast
Rare
Probably
NSAID
5 months
20%
15%
83%
Slow
Common
Probably not







Acute rise in plasma cr
Eosinophilia
Sterile pyuria
Positive Hansel stain
(>1% total WBCs are eosinophil)
Active urine sediment with:
WBC, RBC, and WBC casts
Normal or mildly increased protein
excretion (usually no more than 1g/day)
Renal tubular acidosis







ARF
Hypersensitivity reaction (fever, skin rash,
peripheral eosinophilia, and artheralgia)
Hypertension and edema are uncommon
Hematuria, sterile pyuria, leukocyte casts
Eosinophiluria
Mild to moderate proteinuria (< 1gr/day)
Electrolyte abnormalities (hyperkalemia,
RTA, renal sodium wasting
Other conditions associated with
Eosinophiluria
Prostatitis
 RPGN
 Bladder Cancer
 Renal Atheroembolic disease







CBC
Urinalysis
Hansel stain
Renal ultrasound
Gallium scan
Gold standard is renal biopsy. Indications are:
 Uncertainty of diagnosis
 Advanced RF
 Lack of spontaneous recovery after cessation of offending
drug
 If immunosupressive therapy is considered
 Discontinue offending agent!!
 Most cases improve spontaneously
 Prednisone (1mg/kg/day)
for minimum of 1-2 weeks
 Much less commonly used
Mycophenylate mofetil
Cyclosporine
Cyclophosphamide

Myoglobinuria: rhabdomyolysis.

Hemoglobinuria: intravascular hemolysis.




The urine may have a low FENa despite tubular
injury.
Positive dipstick test for heme pigment without
red blood cells on microscopic exam should
suggest myoglobinuria or hemoglobinuria.
Heme-pigmented granular casts.
Plasma is normal color in myoglobinuria and red
brown in hemoglobinuria.
Resultant effects of derangements due to
rhabdomyolysis and reperfusion











Potassium 
Hyperkalemia

Calcium 
Hypocalcemia

Phosphate 
Hyperphosphatemia
Myoglobin
Myoglobinemia 
Fluid shifts
Hypovolemia

Reperfusion
Free radicals 
Purines

Hyperuricemia 
Hypoxemia
Lactic acid

Thromboplastin Complement system
Creatinine 
Elevated serum levels
Sodium 
Hyponatremia
ARF
Arrhythmias
Arrhythmias
Renal damage
Renal damage
Renal failure
Renal damage
Renal damage
Acidosis
DIC

Delay in treatment associated with greater
morbidity and mortality
50% renal failure at 6 hours
 100% renal failure at 12 hours
 Rhabdomyolysis induced renal failure
has 40% mortality

ARF

Fluid resuscitation before victim extricated
 1 L NS bolus, followed by 1-1.5 L per hour
Limb stabilization
 Minimize potential systemic effects of
reperfusion

 Use of tourniquets prior to release
Alkalinization by giving 1 ampule of
sodium bicarbonate (50 mEq) immediately
prior to extrication, followed by adding 1
ampule of sodium bicarbonate to each liter
of NS infused at 1-1.5 L per hour
 keep second IV line open without sodium
bicarbonate

ARF

Transfusion reactions due to ABO incompatible blood
are probably the most frequently encountered
hemolytic processes that can lead to acute renal failure.

Severe acute hemolytic episodes in patients with
glucose-6-phosphate dehydrogenase deficiency.
Common Nephrotoxic Agents
• Antimicrobial agents
– Aminoglycosides
– Amphotericin B
– Acyclovir
– Foscarnet
– Pentamidine
• Chemotherapeutic agents
– cisplatin
– mitomycin C
– streptozocin
• Vasoactive drugs
– NSAIDS
– ACE inhibitors
– CSA and tacrolimus
• Radiocontrast agents
Aminoglycoside Nephrotoxicity
•
•
•
•
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(CIN)
• 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
•
•
•
•
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
Prevention of Radiocontrast Nephropathy
Intervention
Strength of
Evidence
Clarity of
Risk-Benefit
Grade of Recommendation
Volume expansion
with normal saline
Good
Clear
A: Intervention is always indicated
and acceptable
Volume expansion
with sodium
bicarbonate
Fair
Clear
B: Intervention may be effective and is acceptable
Iso-osmolar contrast
Fair
Clear
B: Intervention may be effective and is acceptable
Theophylline
Fair
Unclear
C: May be considered; minimal or
no relative impact
N-acetylcysteine
Good
Unclear
C: May be considered; minimal or
no relative impact
Hemofiltration
Fair
Unclear
I: Insufficient evidence to recommend for or against
Fenoldopam
Good
Unclear
D: Not useful
Hemodialysis
Good
Unclear
D: Not useful
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
Acute Urate Nephropathy
• Acute oliguric renal failure associated with urate levels >
18 mg/dl
• Associated with overproduction and excretion of urate in
patients undergoing chemotherapy or with a heavy tumor
burden
• Urine urate/creatinine > 1
• Prevention: allopurinol 600-900 mg/d + NS (uo > 2.5 l/d)
• Urinary alkalinization may worsen calcium phosphate
precipitation and NS is as effective as urinary alkalinization
alone
• Early dialysis indicated for oliguric ARF to decrease urate
burden
Renal Disease Associated
with Multiple Myeloma
• Myeloma cast nephropathy
– direct precipitation of casts in tubules
– Factors favoring cast precipitation:
-affinity of light chains for Tamm-Horsfall protein
-high luminal Cl-volume depletion
– Plasmapheresis may be beneficial
• Hypercalcemic nephropathy
• Glomerular lesions (MPGN, Amyloid, Light chain deposition
disease)
AKI: Glomerulonephritis (RPGN)
• 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
•
•
•
•
•
TTP
HUS
Scleroderma renal crisis
Preeclampsia
Malignant hypertension
Acute Glomerulonephritis (RPGN)
• Accounts for a minority of AKI: ~5%
• May have severe morbidity, mortailty
• Extra-renal manifestations may be present
•
•
•
•
Pulmonary
Dermal
GI
Hematologic
• HTN may be present, especially in absence of prior Hx
• UA: differentiates from ATN, AIN
• Dysmorphic RBC, RBC casts, proteinuria > 0.5gm/24h
• Serologies, complement activation
• Need for specific therapy to reduce Ab critical towards
attenuating/reversing AKI
Acute Glomerulopathies
• RPGN most commonly seen with:
– Lupus nephritis (DPGN, class IV)
– Pauci-immune GN (ANCA associated)
– Anti-GBM disease
– less commonly: IgA, post-infectious
• Nephrotic presentations of ARF
– Collapsing FSGS (HIV nephropathy)
– Minimal change disease with ATN
• Thrombotic microangiopathies (HUS, TTP, malignant
hypertension, scleroderma kidney, pre-eclampsia)
Atheroembolic Renal Disease
• ARF in patient with erosive atherosclerosis
• Often follows aortic manipulation (angiography, surgery,
trauma) or anticoagulation
• Pattern is often an acute worsening of renal function due to
showering of emboli, followed by more insidious progression
over several weeks to months due to ongoing embolization of
atheromatous plaques
• Livedo reticularis
• Nephritic sediment, eosinophilia, eosinophiluria, low C3
• Poor prognosis
Livedo reticularis
• Patient with lupus and
anti-phospholipid
antibodies with livedo
reticularis (manifested by
a reddish-cyanotic,
reticular pattern of the
skin) which has resulted in
ulcer formation (arrows).
Courtesy of Samuel
Moschella, MD.
Hollenhorst plaque (cholesterol
cyrstal, arrow) in retinal artery
• Reproduced with
permission from:
Digital Reference of
Opthalmology,
Edward S. Harkness
Eye Institute,
Columbia University,
NY.
Hepatorenal Syndrome
Major Criteria
•
•
•
•
•
Chronic or acute liver disease with advanced hepatic failure and portal
hypertension
Low GFR, as indicated by a serum creatinine >1.5 mg/dL or a creatinine
clearance < 40 mL/min
Absence of shock, ongoing bacterial infection, fluid loss, and current or
recurrent treatment with nephrotoxic drugs. Absence of gastrointestinal fluid
losses (repeated vomiting or intense diarrhea) or renal fluid losses (as indicated
by weight loss > 500 gm/d for several days in patients with ascites without
peripheral edema or > 100 gm/d in patients with peripheral edema)
No sustained improvement in renal function (decrease in serum creatinine to
1.5 mg/dL or less or increase in creatinine clearance to 40 ml/min or more)
after withdrawal of diuretics and expansion of plasma volume with 1.5 L of
isotonic saline
Proteinuria < 500 mg/d and ultrasonographic evidence of obstructive uropathy
or parenchymal renal disease.
Hepatorenal syndrome
Minor Criteria
•
•
•
•
Urine volume < 500 mL/day
Urine sodium < 10 mEq/L
Urine osmolality > plasma osmolality
Serum sodium concentration < 130 mEq/L
Other AKI….
• Abdominal Compartment Syndrome
– Presence of IAP >20 that is associated with a single or multiple organ
system failure. Causes severe oliguric or anuric renal failure. Tx:
surgical decompression.
• Acute Phosphate Nephropathy
– AKI from Nephrocalcinosis after use of oral sodium phosphate
(phospho soda) for colonoscopy.
• Orlistat associated AKI
– AKI from Oxalate nephropathy due to enhancing oxalate absorption
with increased urinary excretion.
• IVIG associated AKI
– AKI from osmotic nephrosis from sucrose-containing formulation.
• Herbal, Home remedies
– Arsenal X, Chromium picolinate, Chineses Herb Xi Xin with aristolochic
acid; tea from Mouring Cypress, Snake gallbladder, Star fruit (oxalate),
Ma Huang (ephedra), Noni Juice






BUN and serum cr
CBC, peripheral smear, serology
Urinalysis
Urine electrolytes
U/S kidneys
Serology: ANA,ANCA, Anti DNA, HBV, HCV,
Anti GBM, cryoglobulin, CK, urinary Myoglobulin
ARF
Daily rise in Noncatabolic Catabolic &
& Nonoliguric
Oliguric
10 – 20
BUN (mg/dl)
20 -100
Cr (mg/dl)
0.5 – 1
>2
K (mEq/l)
< 0.5
1 – 2 (more)
<1
>2
Hco3 (mEq/l)

Urinalysis
Unremarkable in pre and post renal
causes
 Differentiates ATN vs. AIN. vs. AGN

 Muddy brown casts in ATN
 WBC casts in AIN
 RBC casts in AGN

Hansel stain for Eosinophils

Urinary Indices;
UNa x PCr
FENa = —————— x 100
PNa x UCr
FENa < 1% (Pre-renal state)
 May be low in selected intrinsic cause
 Contrast nephropathy
 Acute GN
 Myoglobin induced ATN
 FENa > 1% (intrinsic cause of ARF)
ARF
Diagnostic Index
Prerenal
Azotemia
Intrinsic
Azotemia
>1.018
<1.012
> 500
< 250
BUN / Cr
>20
<10 - 15
Urinary Na conc.(mEq/l)
<10
>20
Fractional Excretion of
Na(%)
UNa×Pcr×100 / PNa×Ucr
Urine sediment
<1
>1
Hyaline casts
Muddy brown
granular casts
Urine SG
Urine Osmolality

Laboratory Evaluation:
 Scr, More reliable marker of GFR
 Falsely elevated with Cimetidine,….
 small change reflects large change in GFR

BUN, generally follows Scr increase
 Elevation may be independent of GFR
 Steroids, GIB, Catabolic state, hypovolemia

BUN/Cr
 ratio> 20:1 suggests prerenal cause
ARF
Indications for Renal Biopsy in AKI:
 Acute nephritic syndrome
 Hematuria, cellular casts, proteinuria in setting of newonset or exacerbation of HTN, rising SCr
 May also have serologic (+) i.e. ANA, ANCA, aGBM that
tissue dx also provides treatment options and prognosis

Unexplained AKI
 Uncertain or multiple competing ddx, of which treatment
differs greatly with definitive dx; AIN vs ATN
 Young pts with AKI often are considered based on longterm renal survival outcomes maximized with definitive
dx
ARF
Azotemia
R.Ultrasound
R.Size &
parechyma
+
Hydronephrosis
Small kidneys
Thin cortex
Nr. size kidneys
Intact
parechyma
CRF
Urinalysis
ARF
Urologic eval.
Urinalysis
Normal
Abnormal
Urine
Electrolytes
WBC, WBC
cast,
Eosinophils
Bacteria
AIN
Pyelonephritis
RBC cast,
proteinuria
AGN
or vasculitis
RBC
Large vessel
occlusion
ARF
Muddy brown
casts
ATN
Differential diagnosis of acute renal failure
98
99
101
ARF
104
106
Hydronephrosis
Normal Renal Ultrasound
Hydronephrosis
Hydronephrosis

Strategies that are likely to be effective
Isotonic hydration (IV route)
Once-daily dosing of aminoglycosides
Use of lipid formulations of amphotericin B
 Use of iso-osmolar nonionic contrast media




Strategies of unknown efficacy




NAC
Theophylline
Low-dose recombinant ANP (in cardiac surgical patients)
Strategies that are not effective




Loop diuretics
Dopamine and dopamine receptor agonists
ANPs
Prophylactic hemofiltration
The best approach to post-ischemic ATN is
to prevent its development.
1. Identify persons at high risk for AKI, such
as:





CKD
Atherosclerosis
DM
Advanced malignancy
Poor nutrition
2. Identify settings in which patients are
subjected to procedures that may induce
post-ischemic ATN:

Major surgery particularly:
 Cardiac surgery
 Abdominal aortic aneurysm surgery
 Surgery to correct obstructive jaundice



Sepsis
Marked hypovolemia
Severe pancreatitis
 In patients at increased risk or early in
the ischemic phase non-pharmacologic
interventions are suggested, including:
 Optimizing volume status with IV fluids
 Maintenance of adequate hemodynamic
status to ensure renal perfusion
 Avoidance of further injury by removing or
decreasing the effect of any nephrotoxins

Diuretics







Loop diuretics
Mannitol
Dopamine
Fenoldopame
ANP
Adenosine Antagonists
Intensive insulin therapy


Amino acids (Glycine and Alanine)
Antiapoptotic/necrosis agents




Minocycline
Guanosine
Pifithrin-alpha
Poly ADP-ribose polymerase (PARP) inhibitor [5aminoisoquinolinone (5-AIQ)]

Free radical scavengers
Deferoxamine
 Pyruvate


Growth factors
Erythropoiethine
 HGF
 IGF-1


Vasodilators



Anti-inflammatory drugs



Tezasartan, a dual ET-1 receptor antagonist
Heme oxygenases (Hos)
Anti-ICAM-1 antibodies and synthetic RGD
peptides (arginine-glycine-aspartic acid)
Statins
Enhancing tubular cell regeneration by
infusion of stem cells


Antioxidants
Other compounds:




Neutrophil gelatinase-associated lipocalin
IL-6 and C5a antagonists
IL-10
Ghrelin (a compound with a GH releasing effect)

Diuretics should NOT be administered as
prophylaxis for post-ischemic ATN



Clinical Outcomes:
 No effect on mortality
 No effect on the need for or incidence of RRT
Renal Physiologic Outcomes:
 Diuretic effect and increased cr clearance on
the first day which was not significant on the
following days.
Adverse effect:
 on the immune, respiratory, and endocrine
system.
Tachycardia
2. Arrhythmias (particularly among
1.
cardiac surgery patients)
Myocardial ischemia
4. Intestinal ischemia (due to
3.
precapillary vasoconstriction)
o
o
o
o
Dop-1 receptor agonist, lack of Dop-2, and
a-1 receptor effect, make it a potentially
safer drug than Dopamine!
Reduces in hospital mortality and the need
for RRT in AKI
Reverses renal hypoperfusion more
effectively than renal dose Dopamine
So far so good specially in cardiothoracic
ICU patients


ANP is a 28 AA polypeptide
synthesized in cardiac atrial muscle.
ANP augments GFR by:




Afferent arteriolar vasodilatation
Inhibit the RAS
Inhibits Na transport & lowers oxygen
requirements in several nephrone segments
ANP analog: Anaritide


ANP may be associated with improved
outcomes when used in low doses for
preventing AKI and in managing
postsurgery AKI.
There were no significant adverse events
in the prevention studies, however in the
high dose ANP treatment studies there
were significant increases hypotension
and arrhythmias.

Adenosine, in contrast to its general systemic
effect as a vasodilator, is a renal arterial
vasoconstrictor.



Increases afferent arteriolar tone in response to
increased distal tubular solute delivery.
Acts synergistically with Ang II to constrict
afferent arterioles.
Possible mediator of the intrarenal hemodynamic
changes that lead to ATN following radiocontrast
administration.


Patients who received theophylline had
a smaller increase in serum cr .
It remains unclear if theophylline might
be useful preventing contrast
nephropathy in some patients.


Currently no evidence of protective effect
Causes an osmotic diuresis with may benefit fluid
balance
Increasing flow through tubules,
preventing obstruction
 Osmotic action, decreasing endothelial
swelling
 Decreased blood viscosity with increased
renal perfusion (???)
 Free radical scavenging

ARF

Strategies that are likely to be effective





Strategies of unknown efficacy




Isotonic hydration (IV route)
Once-daily dosing of aminoglycosides
Use of lipid formulations of amphotericin B
Use of iso-osmolar nonionic contrast media
NAC
Theophylline
Low-dose recombinant ANP (in cardiac surgical patients)
Strategies that are not effective




Loop diuretics
Dopamine and dopamine receptor agonists
ANPs
Prophylactic hemofiltration

Neutrophil GelatinaseAssoc. Lipocalin
(NGAL)


Cystatin C



Levels in blood and urine
rise within a few hours
after injury
Absorbed by kidney, but
not secreted
Rises one day before Cr
Interleukin 6&18


Produced by caspase-I
which is implicted in
pathogenesis of ARF
KIM-1
Have been shown to predict AKI severity in post-op
hearts
131

Frusemide
Theoretically may reduce tubular injury
Due to shutting down Na/K/Cl ATPase
Reduces oxygen demand
May help with fluid balance
Reduced energy consumption in the critical outer
medulla (by 45% in-vitro)
 Wash out tubular debris






But




No clinical evidence
Accumulates in Oliguria
Nephrotoxic and Ototoxic
May actually increase mortality and or need for RRT
ARF

Dopamine
Low dose Dopamine (2-3µg/kg/min),
known as “renal dose”
 No effect on mortality or need for
Renal replacement therapy

ARF

Vasopressors and AKI
Although Noradrenaline causes
vasoconstriction with renal
vasculature
 No evidence of worsening AKI
 But should be used after adequate
volume resuscitation

ARF

Mannitol


Currently no evidence of protective effect
Causes an osmotic diuresis with may benefit fluid
balance
Increasing flow through tubules,
preventing obstruction
 Osmotic action, decreasing endothelial
swelling
 Decreased blood viscosity with increased
renal perfusion (???)
 Free radical scavenging

ARF

ANP


Theophyline


Improve renal function and decrease renal
insufficiency
Adenosine antagonist – prevents reduction in GFR.
Growth Factors

After ischemic insult, infusion of IGF-I, Epidermal GF,
Hepatocyte GF improved GFR, diminished
morphologic injury, diminished mortality
None of these things are well tested….
ARF

Maintenance of blood flow
 Cardiac output, isovolemia, etc
Avoidance of toxins
 Aminoglycosides, amphoteracin,
NSAIDs,…

Dose adjustment of drugs

Easy on paper….difficult in practice

ARF
1.
2.
3.
4.
5.
6.
7.
8.
Prevent it in the First Place!!
Treat / Remove the Cause
Restore adequate circulating Volume
Restore adequate blood pressure
Restore adequate flow
Control fluid intake
Wait, Patience is a virtue!
Renal replacement therapy
ARF

Nutrition management
 Initially very catabolic
 Goals:
 Adequate calories
 Low protein
 Low K and Phosphate
 Decreased fluid intake
ARF









Severe fluid overload
Refractory hypertension
Uncontrollable hyperkalemia
Nausea, vomiting, poor appetite, gastritis with
hemorrhage
Progressive uremic encephalopathy (lethargy,
malaise, somnolence, stupor, coma, delirium,
asterixis, tremor, seizures)
Pericarditis (risk of hemorrhage or tamponade)
bleeding diathesis (epistaxis - GI bleeding and etc..)
attributable to uremia
Severe metabolic acidosis
BUN > 70 – 100 mg/dl

When initiated?
 When uremia can no longer be
managed conservatively.
 Immediately when:
 Fluid overload unresponsive to diuretics
 Pericarditis
 Neurologic manifestations
 GI manifestations
 Unresponsive hyperkalemia
 Unresponsive acidosis
ARF
Prevention
Cause Prevention
✔✔
Treatment
Loop Diuretics
Loop Diuretics
↔
Natriuretic
Peptides
Osmotic Diuretics
↔
Dopamine
↔
Dialysis Mode
✔
Dialysis
Dosing
Ca Channel
Blockers
N-Acetylcysteine
Theophyllines
↔
ARF
↔
↔
↔
↔
✔ High dose