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Transcript
Acute Renal
Failure
Syed Rizwan, MD
1
Acute Renal Failure


Comprises a family of syndromes
Abrupt decrease in GFR(over
hours to days)
2
MANIFFESTATIONS of
ARF



Increase in BUN
Increase in creatinine
Oligouria(< 400 –500 cc)
3
DEFINITION





No consensus
Multiple
Relative rise in Serum Creatinine
> 0.5mg/dl if baseline creatinine is
normal
> 1 mg/dl if baseline serum
creatinine is high
4
Creatinine and GFR
 Creatinine
produced in muscles
 Creatinine excretion depends on,
• Glomerular filtration
• Proximal tubular excretion
 Change
in Serum Creatinine with
no change in GFR
• Muscle wasting or amputation lowers
creatinine
• Medications(Trimethoprim,
Cimetidine) increase creatinine by
deceasing tubular excretion
5
Blood Urea and GFR

Increase BUN with no change in GFR






GI Bleed
Hyper catabolic states
Protein loading
Glucocorticoids
Tetracycline
Decrease BUN with no change in GFR


Protein Malnutrition
Severe Liver disease
6
ARF and Biomarker




Lack of sensitivity of BUN and
creatinine
Need for Biomarkers
Kidney Injury Molecules-1(KIM-1)
increased in Patients with Acute
Tubular Necrosis
None available for cliniical utility
yet
7
Epidemiology of ARF




Incidence, etiology and outcome
varied depending on Population
studied and Definition used
Mostly in-Patient than out –Patient
5-7% of hospital admissions
Mortality varies between 20%-85%
depending on cause
8
ARF Classification



Prerenal
Renal
Postrenal
9
Prerenal ARF



Hemodynamically mediated
reduction in GFR in absence on
Renal Parenchymal injury.
ARF resolves if hemodynamic
insult is reversed
If hemodynamic insult is sustained,
can result in overt renal injury
10
Renal ARF

Renal Parenchymal injury
11
Postrenal ARF

Acute obstruction to the Urinary
Tract
12
Prerenal Azotemia

Decreased Glomerular
perfusion(no renal injury)
True Volume Depletion e.g.
Diarrhea
 Effective Volume Depletion,
cirrhosis
 Altered Intrarenal Hemodynamics
e.g. ACEI

 Affenet
dilatation
 Efferent vasoconstriction
13
Prerenal Azotemia

True or Effective Volume depletion,
Neurohumoral vasoconstrictor
 Increased catecholamine
 Renin-angiotensin system
activation
 Increased vasopressin release

14
Renal Autoregulation


Maintains Glomerular Blood Flow
and thus GFR
Afferent Vasodialtaion,
Prostaglandins
 Kallikrein-kinin
 Myogenic influence
 Nitiric oxide


Efferent vasoconstriction

Angiotension 11
15
Prerenal Azotemia

Prerenal ARF presents with
Oligouria
 Low Urine Na from Na retention
 Increased BUN :creatinine ratio
>20:1
 FENa < 1%


Existing Renal Insufficiency or
Diuretic can alter this picture
16
ARF and ACEI &ARB

ACEI & ARB have greatest
benefits in Patients with high risk of
ARF
Old age
 Diabetics
 Cardiomyopathy
 CHF with higher dose oh Diuretic
 Renal Vascular disease
 Chronic Kidney disease

17
Prerenal ARF with ACEI
&ARB







Efferent Vasodilatation deceases
GFRmedications
Lower GFR raises serum creatinie but
usually less than 30%
Must monitor serum creatinine and
electrolytes before and after starting or
changing dose of these medications
Stop if ARF
Correct volume status
W/u for renal Artery Stenosios
Can reintroduce cautiously if reversible
factors corrected
18
Prerenal ARF & NSAIDs



Both COX1/Cox!! Inhibitors cause lower
Prostaglandins synthesis
Impairs Afferent vasodilatation decrease
Glomerular perfusion
Effect greatest in high risk population





CHF
Cirrhosis
CKD
Vascular disease
elderly
19
Abdominal
Compartment Syndrome



Unusual cause of ARF
Associated with increased intraabdominal pressure
Manifestations,







Respiratory compromise
Decreased cardiac output
Intestinal ischemia
Hepatic Dysfunction
Oliguric ARF
Increased renal venous pressure
Recovery with decreased intraabdominal
pressure
20
Post-Renal ARF




Obstruction – complete or Partial
Anuria or variable urine output
Recovery depends on duration of
obstruction
Conditions Sonogram may not show
obstruction,




Retroperitoneal fibrosis
Tumors
Adenopathy
Encasing ureter prevent dilatation
21
ARF- Renal


Useful to categorize according to
Anatomical injury.
Primary sites,






Glomerulus- Acute Glomerulonephritis
Tubules- Acute Tubular Necrosis
Interstitium- Acute Interstial Nephritis
Vascular- Atheroembolism
ATN- most common
U/A-Protein, RBC,Casts,pigments
22
Acute Tubular Necrosis





Ischemic vs Nephrotoxic
Most frequently multi-factorial
Medical vs Surgical
Ischemic- Hypotension,shock
Nephrotoxic- Dye induced,
Rhabdomyolysis
23
Acute Tubular Necrosis




Initiation, maintenance, recovery
Phases
Mortality from very low to very high
Potentially Preventable
Long –term outcome in survivors
very good
24
ATN- Specific
Syndromes




Radiocontrast Nephropathy
Rhabdomyolysis
Aminoglycoside Related
Amphotericin B associated
25
Radiocontrast
Nephropathy



10% of Hospital acquired ATN
Mild and Transient in Majority
Risk factors,







Amount of Dye(> 100cc)
Volume Depletion
Renal Insufficiency
DM
Old Age
CHF
ACEI or NSAIDs
26
Radiocontrast
Nephropathy

Risks higher with higher creatinine
Normal- negligible risks
 Mild- Moderate RI(Creatinine< 2)–
5-10% risks
 Mild- Moderate RI with DM- 1040% risks
 Advanced Renal Disease- >50%

27
Radiocontrast
Nephropathy




Pathogenesis incompletely
understood
Severe Renal vasoconstriction
within seconds of contrast
administration
Direct Renal Tubular injury
FENa < 1%
28
Radiocontrast
Nephropathy










Independent risk factor of death
Prevention in high risk Patients
Consider Alternate imaging.g. MRI
Volume repletion with Saline
Minimize amount of Dye
Low Osmolality contrast media?
N-Acetylcysteine(Mucomyst)?
Fenoldopam-Selective Dopamine
agonist?
Lasix, Mannitol, Dopamine –not helpful,
may be risky
Prophylactic Hemodialysis- not helpful 29
Radiocontrast
Nephropathy




N-Acetylcysteine – reducing agent,
scavenge reactive oxygen species(ROS)
No good large randomized trial to prove
its efficacy
Impact on morbidity and mortality
unknown
Used commonly in practice b/o potential
benefits and lack of Toxicity
30
Aminoglycoside
Nephrotoxicity






Usually after 7-10 days
Depends on dose and frequency
Direct Proximal Tubular injury
Once a day dosing may be less
Nephrotoxic
K. Ca. MG wasting
Risk factors- age, Renal
insufficiency, Dose,Volume
depletion
31
ARF from
Rhabdomyolysis



Muscle injury leading to ARF
Most cases subclinical
Myoglobinuria cause,






Renal vasoconstriction
Proximal tubular damage
Intratubular cast (Obstruction)
Hypovolemia(Third Spacing)
Metabolic Acidosis,
Electrolyte Imbalance(K,Ca,P)
32
ARF from
Rhabdomyolysis

Subclinical causes more common
Drugs
 PVD
 Seizure





FENa < 1%
U/A- Heme/+vie but no RBC
Aggressive Volume replacement
Urinary Alkalization?, Mannitol?
33
Amphotericin B
Nephrotoxiciy








Very high incidence of ARF
Binds to sterol in cell membrane
Multiple sites in Nephrons
Distal Tubular Acidosis
Mg and K wasting
Dose dependent
Liposomal Amphotercin formulation less
toxic
Saline loading helpful
34
Postoperative ARF





ARF after vascular,cardiac and
major abdominal surgery.
Very high mortality
Multifactorial
1-5% after CABG.
Risk factors,

Renal disease, cardiogenic shock,
emergent surgery, Left main
disease etc,
35
Acute Interstitial
Nephritis







Classical triad(fever rash & eosinophilia)
not usually seen
Mostly Drug related e.g. Cipro
Infection : Strept., Staph, CMV, EB virus,
Hantaan virus etc
Systemic Diseases : SLE, Sarcoidosis.
Eosinophiluria may be absent
Dx by renal Biopsy.
Rx supportive, Hold Drug, Steroids ?
36
Atheroembolic ARF







Require high degree of suspicion
Cholesterol emboli
Renal failure – acute or subacute
Multisystem disorder
Lived reticularis
Digital Ischemia(Blue Toe
Syndrome)
GI bleed, TIA, Rahbdomyolysis
37
Atheroembolic ARF






ARF after vascular procedure
ARF can be abrupt needing dialysis
within few days.
Can be subacute occurring in staggered
steps separated by stable renal function.
Patients on Anticoagulants are at high
risk
Eosinphilia, eosinphiluria, low
complement.
High mortality
38
Hepatorenal Syndrome






Profound renal vasoconstriction
Resemble Pre-renal Azotemia
Volume Expansion fail to improve
renal function.
Pathogenesis incompletely
understood
Oligiuric ARF, FENa low
Diagnosis of exclusion
39
Hepatorenal Syndrome






Two Types
Type 1 HRS: rapid ARF,
hospitalized Pt.,>90% mortality
Type 11 HRS : insidious onset,
slow progression of RI, refractory
ascites, better prognosis.
ATN vs HRS
Low FENa I n ATN
casts in Bilirubinemia with HRS
40
Hepatorenal Syndrome






Rx difficult
Volume expansion with Albumin
Terlipressin(vasopressin analogue)
Midodrine (selective alpha 1
adrenergic agonist)+ octreotide(a
somstoastatin analogue)
TIPS, Liver Transplantation
Dialysis in selective Patients
41
ARF in HIV/AIDS







Prerenal Azotemia
Renal salt wasting from Adrenal
Insufficiency.
HIV Nephropathy
High risk for ATN
Drug side effects e.g. Pentamidine.
Crystal nephropathy(indinavir)
TTP(prognosis worse )
Rhabomyolysis
42
ARF from RPGN








Less common
Rapidly Progressive Glomerulonephritis
include vasculitis, SLE, Wagner's
Active Urinary sediments(RBC cast
diagnostic)
Higher degree of Proteinuria
Serology helpful(ANCA,
ANA,IgMantibodyetc0
Renal Biopsy usually required.
Early diagnosis essential to prevent
ESRD
Rx with Steroids and Cytoxan
43
Rx of ARF






No proven Drugs
Many cause preventable
Volume expansion
Withdrawal of Drugs
Diuretics help in management but
not curative
Dopamine potentially harmful
44
RRT in ARF


Renal Replacement Therapy usually the
only option in severe ARF.
Indication of RRT






HYPERKALEMIA
METABOLIC Acidosis
Uremic Symptoms
Fluid Load
“Prophylactic”
RRT




Intermittent Hemodialysis
CVVHD
Extended Daily Dialysis(6-12h)
Peritoneal Dialysis- not favored
45
CVVHD vs Hemodialysis

HD –


CVVHD


more stable Pt, SBP >90, no heparin,
allows larger amount of fluid removal
in3-4 hours
Unstable Pt., low BP with high dose
Pressers, allows gradual removal of fluids
24h
EDD

Allows no heparin dialysis, gradual
removal of fluids, but expensive b/o
Nursing Support
46
RRT- how to improve
outcome?




Lot of Questions to answer
Frequency of Dialysis
Quantification of Dialysis
Type of Membrane of Dialysis



Synthetic vs. Cellulose
Does Erythropoietin improves
outcome?
Faster fluid removal vs. slow fluid
removal?
47