Acute Renal Failure

Syed Rizwan, MD

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Acute Renal Failure
 Comprises a family of syndromes
 Abrupt decrease in GFR(over
hours to days)

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MANIFFESTATIONS of
ARF
 Increase in BUN
 Increase in creatinine
 Oligouria(< 400 –500 cc)

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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

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Creatinine and GFR
 Creatinine produced in muscles
 Creatinine excretion depends on,
• Glomerular filtration
• Proximal tubular excretion

 Changein Serum Creatinine with

no change in GFR
• Muscle wasting or amputation lowers
creatinine
• Medications(Trimethoprim,
Cimetidine) increase creatinine by
deceasing tubular excretion

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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

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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

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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

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ARF Classification
 Prerenal
 Renal
 Postrenal

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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

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Renal ARF
 Renal Parenchymal injury

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Postrenal ARF
 Acute obstruction to the Urinary
Tract

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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

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Prerenal Azotemia
 True or Effective Volume depletion,
 Neurohumoral vasoconstrictor
 Increased catecholamine

 Renin-angiotensin system

activation
 Increased vasopressin release

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Renal Autoregulation
 Maintains Glomerular Blood Flow
and thus GFR
 Afferent Vasodialtaion,
 Prostaglandins
 Kallikrein-kinin

 Myogenic influence

 Nitiric oxide

 Efferent vasoconstriction
 Angiotension 11

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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

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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

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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

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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

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Abdominal Compartment
Syndrome
 Unusual cause of ARF
 Associated with increased intra-abdominal
pressure
 Manifestations,
 Respiratory compromise
 Decreased cardiac output
 Intestinal ischemia
 Hepatic Dysfunction
 Oliguric ARF
 Increased renal venous pressure
 Recovery with decreased intraabdominal
pressure

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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

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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

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Acute Tubular Necrosis
 Ischemic vs Nephrotoxic
 Most frequently multi-factorial
 Medical vs Surgical
 Ischemic- Hypotension,shock
 Nephrotoxic- Dye induced,
Rhabdomyolysis

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Acute Tubular Necrosis
 Initiation, maintenance, recovery
Phases
 Mortality from very low to very high
 Potentially Preventable
 Long –term outcome in survivors
very good

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ATN- Specific Syndromes
 Radiocontrast Nephropathy
 Rhabdomyolysis
 Aminoglycoside Related
 Amphotericin B associated

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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

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Radiocontrast
Nephropathy
 Risks higher with higher creatinine
 Normal- negligible risks
 Mild- Moderate RI(Creatinine< 2)–

5-10% risks
 Mild- Moderate RI with DM- 10-

40% risks
 Advanced Renal Disease- >50%

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Radiocontrast
Nephropathy
 Pathogenesis incompletely
understood
 Severe Renal vasoconstriction
within seconds of contrast
administration
 Direct Renal Tubular injury
 FENa < 1%

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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

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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

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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
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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)

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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?
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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

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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,

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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 ?

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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
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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
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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

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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
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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

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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
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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

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Rx of ARF
 No proven Drugs
 Many cause preventable
 Volume expansion
 Withdrawal of Drugs
 Diuretics help in management but
not curative
 Dopamine potentially harmful

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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

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CVVHD vs Hemodialysis
 HD –
 more stable Pt, SBP >90, no heparin,
allows larger amount of fluid removal in3-
4 hours
 CVVHD
 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

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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?
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