Percy Pentecost MD
Objectives
To understand:
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3 major etiologies of ARF
• Pathophysiology of:
• prerenal ARF
• Postrenal ARF
• Intrarenal ARF
• Basic evaluation and treatment of ARF
Definitions
• Acute Renal Failure: abrupt and sustained decline in renal
function resulting in an accumulation of nitrogenous waste
products and uremic toxins
• Oliguria: Urine output less than 400 mL/ 24°
• Anuria: Urine output less than 100 mL/ 24°
• Azotemia: Increase in serum concentration of nitrogenous
waste products
Incidence
• Community Acquired ARF:
• Prerenal70% of cases
• Mortality 7%
• Hospital Acquired ARF:
• 15-20% of ICU patients
• Ischemic or Toxic injury in 60% of these cases
• Mortality 50-70%
Risk Factors
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Advanced Age
Preexisting Renal Disease
Diabetes
Cardiac Disease
Liver Disease
• “Older Sicker Patients
• “Internal Medicine Patients”
3 Major Etiologies of ARF
• Prerenal
• “before the kidney”
• Postrenal
• “after the kidney”
• Intrarenal
• “within the kidney”
Prerenal Factoids
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Very Common
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Often reversible within 24-48 hours
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Caused by renal hypoperfusion and decreased GFR
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Not associated with significant tubular injury…
…unless sustained
Prerenal Causes
• Hypovolemia:
• Hemorrhagic Shock, Dehydration, Liver Failure with Low Albumin
• Low Cardiac Output (real and effective):
• CHF, Drugs*
• Systemic Vasodilation:
• Sepsis, Drugs*, Hepatorenal Syndrome
• Renal Vasoconstriction:
• Renal Artery Stenosis, Embolism, or Disection
Prerenal--Drugs
Changes in tone of afferent/ efferent
arterioles will affect RBF and GFR
ASA and NSAIDS cause this------------------->
ACEIs and ARBs cause this------------------->
Prerenal Diagnosis
• Bun to Creatnine greater than 20 / 1 Classically
• FENa < 1% and Urine Sodium is low (<20)
• Kidneys avidly absorbing Na to increase perfusion pressure
• Urine Osms and SG are high
• Urine is concentrated
• Urine Sediment is bland (Minimal RBCs and WBCs)
• No tubular / glomerular injury or inflamation
• History suggests
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Nausea, vomiting, diarrhea, immobile with no access to water, etc…
Prerenal--Treatment
• Supportive Care
• Improve Renal Hemodynamics
• IVFs
• Minimize Nephrotoxic drugs
• Stop ACEi, NSAIDS
• Prevention
• Recognize Early
Postrenal Failure Factoids
• 5% of all cases of acute renal failure
• Corrected within 1 week of onset prognosis excellent
• Persists > 12 weeks: interstitial fibrosis / tubular atrophy
• Irreversible
• Variable presentation:
• Anuria with complete obstruction
• Polyuria alternating with oliguria in partial obstruction
• Post-obstructive diuresis may lead to volume depletion
Postrenal Causes
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Urethral:
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Ureters
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Urethral Stricture
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Stones
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Clogged Foley
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Sloughed Papilla
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BPH
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AAA
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Abdominal Cancers
Bladder:
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Bladder Tumor
Abdominal Compartment
Syndrome
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Retroperitoneal Fibrosis
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Lymphadenopathy
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Post Surgical
Neurogenic Bladder
Clots
Postrenal Failure Diagnosis
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Clinical Suspicion Important—Who is going to get this?
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BUN/Cr ratio may be high (like in pre-renal)
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BUN diffuses back into system
K may be high
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Type IV RTA
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UA with blood is common
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FeNa, Urine sodium, Urine Osms: normal
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Ultrasound
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Hydronephrosis
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Obstructing Lesion?
Consider Noncontrast CT for stones
Postrenal Failure Treatment
• Put in Foley (or check for patency)
• Address Underlying Cause
• Urology Consult may be helpful
• Tumor? Stone removal?
• Watch for Post-obstructive Diuresis
Intrarenal--Causes
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Ischemic Tubular Injury (formerly ATN)
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Nephrotoxic Injury (Formerly ATN)
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Acute Interstitial Nephritis
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Intra-tubule Deposition/Obstruction
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Atheroembolic
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Thrombotic Microangiopathy
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Glomerulornephritis
Ischemic and Toxic Injury
Intrarenal Ischemic/Toxic Injury Phases
• Initiation
• Sustained Prerenal state (poor O2 delivery)
• Toxic Injury
• Extension and Maintenance
• Altered transport, adhesion, etc.
• Cell sloughing into tubule lumen
• Leukocytes, cytokines, etc.
• Now vascular blockage too...
• Recovery
• After insults are gone....
Intrarenal Ischemic/Toxic Injury Diagnosis
• Prerenal Azotemia:
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BUN/Cr >20:1
Specific Gravity >1.020
FENA <1%
Uosm > 500
Una <25
Bland Sediment
– Tubules working no signs of
injury
• ATN / AKI:
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BUN/Cr ~10-15:1
Specific Gravity ~ 1.010
FENA >2%
Uosm 300-350
Una > 40
Muddy Brown Casts
– Tubules injured and not
working
Intrarenal Ischemic/Toxic Injury Toxins
Partial List
• Aminoglycosides
• Amphotericin B
• Iodinated contrast
• Cisplatin
• Heme pigments
• Hemolysis
• rhabdomyolysis
Notes
• From ischemic or due to
contrast onset is rapid.
• From aminogylcosides onset
often delayed
• As a general rule, toxic
injury is dose dependent
• Aminoglycosides may be
less toxic given daily
Intrarenal Ischemic/Toxic Injury Treatment
• Remove the insult
• Supportive
• Watch / Replace Electrolytes
• Maintain fluid balance
AIN
AIN Factoids
• AIN = Acute Interstitial Nephritis
• Hypersensitivity drug reaction most common cause
AIN Drugs
• Drugs associated with AIN:
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Beta-lactam antibiotics
Sulfonamides
Vancomycin
Ciprofloxacin
Rifampin
Acyclovir
Captopril
Aspirin
NSAIDS
Diuretics
• More drugs associated with
AIN:
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Polymyxin
Erythromycin
Indinavir
Alpha-interferon
Cimetidine
Allopurinol
Azathioprine
Diazepam
Tetracycline
Phenobarbital
Clofibrate
Indinavir
Carbamazepine
Sulfinpyrazone
Phenindione
AIN Drug Factoids
• Original reports on methicillin-associated AIN reported
occurrence after 10-20 days of drug therapy
• Currently, reported to occur after 7-14 days of therapy
• Can occur within 2-3 days after re-exposure to particular drug
• Can occur de novo in response to previously tolerated drug
(e.g. NSAIDs)
AIN Diagnosis
• “Classic” presentation (less than 30% of patients)
• Elevated Cr
• Fever
• Rash
• Eosinophiluria
• Clinical suspicion is important
• Renal biopsy is gold standard
AIN Treatment
• Supportive
• Discontinue potentially offending drugs
• May need Renal Consult:
• Steroids may help (no RCTs to support)
• Window of therapy for steroids is 7-14 days after onset of azotemia
• Plasmapheresis if anti-tubular basement membrane ABs on biopsy
• Prognosis: Usually reversible if drug stopped quickly (1 week)
Tubular Obstruction
Tubular Obstruction
Pathophysiology:
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Drugs/compounds precipitate in tubules
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Form obstructing crystals
A Partial List:
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Methotrexate
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Intravenous acyclovir
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Sulfadiazine
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Indinavir
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Ethylene glycol toxicity
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Calcium oxalate crystals
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Urate crystal nephropathy
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After cancer chemotherapy
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Light chains in Multiple Myeloma
Tubular Obstruction Diagnosis
• Elevated Uric Acid (Post Chemotherapy)
• SPEP/UPEP (Multiple Myeloma)
• Medication List
• History
Tubular Obstruction Treatment
• Prevention Best Cure
• Adequate Volume
• Specific Therapies in some instances
• Theophyline for Cisplatin
• Supportive
Atheroembolic
Atheroembolic Pathogenesis
• Sometimes occurs spontaneously
• Anticoagulation may precipitate it
• Usually after manipulation of aorta
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Surgery
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Angiography
• Embolization of cholesterol into arterioles and glomerular capillaries
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inflammatory cell infiltrate
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ischemic tubular injury
Atheroembolic Diagnosis
• Cutaneous manifestations: Livedo reticularis, digital infarcts
• Other organs involves: bowel ischemia, CNS disturbance
• Eosinophilia
• Low C3 levels (in some patients—15%)
• Elevated ESR
• History
Atheroembolic Treatment
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Supportive
Treat diabetes, hypertension, dyslipidemia
Discontinue Anticoagulents
Management of vascular risk factors
Prognosis traditionally thought to be poor
• comorbid cardiovascular disease
Thrombotic Microangiopathy
Thrombotic Microangiopathies Etiology
• Pathophysiology:
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Clotting cascade imbalance
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Small vessel blockage and ischemia
• Multiple Precipitating factors
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DIC
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TTP
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Infectious Diarrhea (Ecoli 0157, Shiga Toxin)
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SLE
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HIV
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Drugs
Thrombotic Microangiopathies Diagnosis/Treatment
• Diagnosis:
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Low Platelets on CBC
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RBC fragments on peripheral smear
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Clotting cascade imbalance
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Small vessel ischemia
• Multiple Precipitating factors
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DIC
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TTP
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Infectious Diarrhea (Ecoli 0157, Shiga Toxin)
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SLE
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HIV
Acute Glomerulonephritis
Glomerulonephritis Pathogenesis
• Deposition of complexes in glomeruli
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Cause damage and inflammation
• Many Precipitating Factors
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Bacterial infection
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Group A Strep
Viral Infection
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URI
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Hep C
Rheumatalogic Disease
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SLE
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Vasculitis
Glomerulonephritis Diagnosis
• Urinalysis with “Active Sediment”
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RBCs and WBCS
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Dysmorphic RBCs
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RBC and WBC Casts
• C3 levels Low (C3 represents intrinsic and extrinsic pathway)
• ASO titer (post streptococcal)
• Hepatitis Panel (Hep C)
• Skin Biopsy (IgA Nephropathy and vasculitis)
• RF, ANA, ANCAs, etc. (SLE, vasculitis, etc.)
• Renal Biopsy
Glomerulonephritis Treatment
• Treat Infections
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“breaks the cycle”
• Treat Underlying Diseases
• Steroids and/or Cyclophosphamide
• Renal and Rheumatology Consults
Questions?