Acute Renal Failure

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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(lt 400 500 cc)

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DEFINITION

• No consensus
• Multiple
• Relative rise in Serum Creatinine
• gt 0.5mg/dl if baseline creatinine is normal
• gt 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
• Change in 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 gt201
• FENa lt 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(gt 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(Creatininelt 2) 5-10 risks
• Mild- Moderate RI with DM- 10-40 risks
• Advanced Renal Disease- gt50

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Radiocontrast Nephropathy

• Pathogenesis incompletely understood
• Severe Renal vasoconstriction within seconds of
  contrast administration
• Direct Renal Tubular injury
• FENa lt 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 lt 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.,gt90
  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 gt90, 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?