10 Palevsky   Acute Renal Failure
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10 Palevsky Acute Renal Failure

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    10 Palevsky   Acute Renal Failure 10 Palevsky Acute Renal Failure Presentation Transcript

    • Acute Renal Failure Paul M. Palevsky, M.D. Professor of Medicine Chief, Renal Section VA Pittsburgh Healthcare System
    • Acute Renal Failure
      • Definition
        • The loss of renal function (measured as GFR) over hours to days
        • Expressed clinically as the retention of nitrogenous waste products in the blood
    • Relationship Between GFR and Serum Creatinine in ARF 120 40 80 0 GFR (mL/min) 0 7 14 21 28 4 Days 2 0 6 Serum Creatinine (mg/dL)
    • Acute Renal Failure
      • Definitions
        • Azotemia - the accumulation of nitrogenous wastes
        • Uremia - symptomatic renal failure
        • Oliguria - urine output < 400-500 mL/24 hours
        • Anuria - urine output < 100 mL/24 hours
    • Manifestations of ARF
      • Azotemia progressing to uremia
      • Hyperkalemia
      • Metabolic acidosis
      • Volume overload
      • Hyperphosphatemia
      • Accumulation and toxicity of medications excreted by the kidney
    • Differential Diagnosis of Azotemia
      • Etiologies of acute elevations of BUN
        • Acute renal failure
        • Protein loading
        • GI bleeding
        • Catabolic steroids
        • Tetracycline antibiotics
    • Differential Diagnosis of Azotemia
      • Etiologies of acute elevations of creatinine
        • Acute renal failure
        • Medications that block creatinine secretion
          • cimetidine
          • trimethoprim
        • Substances that interfere with creatinine assay
          • cefoxitin
          • flucytosine
          • acetoacetate
    • Classification of the Etiologies of Acute Renal Failure Acute Renal Failure Acute Tubular Necrosis Acute Interstitial Nephritis Acute GN Acute Vascular Syndromes Intratubular Obstruction Prerenal ARF Postrenal ARF Intrinsic ARF
    • Physiologic Response to Volume Depletion Na Reabsorption AII AII PG RPF GFR P GC FF Urea Reabsorption
    • Prerenal Acute Renal Failure Na Reabsorption AII AII PG RPF GFR P GC FF Urea Reabsorption
    • Pathogenesis of Prerenal Azotemia Renal Vasoconstriction Decreased GFR Angiotensin II Adrenergic nerves Vasopressin + + + Nitric oxide Prostaglandins - - Volume Depletion Congestive Heart Failure Liver Failure Sepsis
    • Prerenal Acute Renal Failure
      • Volume Depletion
      • Decreased effective blood volume
        • congestive heart failure
        • cirrhosis
        • nephrotic syndrome
        • sepsis
      • Renal vasoconstriction
        • hepatorenal syndrome
        • hypercalcemia
        • nonsteroidal anti-inflammatory drugs
    • Prerenal Acute Renal Failure: Clinical Presentation
      • History
        • volume loss (e.g., diarrhea, acute blood loss)
        • heart disease
        • liver disease
        • evidence of infection
        • diuretic use
        • thirst
        • orthostatic symptoms
    • Prerenal Acute Renal Failure: Clinical Presentation
      • Physical Examination
        • Blood pressure and pulse
        • Orthostatic changes in blood pressure
        • Skin turgor
        • Dryness of mucous membranes and axillae
        • Neck veins
        • Cardiopulmonary exam
        • Peripheral edema
    • Prerenal Acute Renal Failure: Clinical Presentation
      • BUN:Creatinine ratio
        • > 20:1
      • Urine indices
        • Oliguria
          • usually < 500 mL/24 hours; but may be non-oliguric
        • Elevated urine concentration
          • U Osm > 700 mmol/L
          • specific gravity > 1.020
        • Evidence of high renal sodium avidity
          • U Na < 20 mmol/L
          • FE Na < 0.01
        • Inactive urine sediment
    • Fractional Excretion of Sodium FE Na = Filtered Sodium Excreted Sodium FE Na = P Na x GFR U Na x V FE Na = U Cr / P Cr U Na / P Na
    • Fractional Excretion of Sodium
      • Etiologies of a fractional excretion of sodium < 0.01
        • normal renal function
        • prerenal azotemia
        • hepatorenal syndrome
        • early obstructive uropathy
        • contrast nephropathy
        • rhabdomyolysis
        • acute glomerulonephritis
    • Treatment of Prerenal Acute Renal Failure
      • Correction of volume deficits
      • Discontinuation of antagonizing medications
        • NSAIDs/COX-2 inhibitors
        • Diuretics
      • Optimization of cardiac function
    • Postrenal Acute Renal Failure
      • Urinary tract obstruction
        • level of obstruction
          • upper tract (ureters)
          • lower tract (bladder outlet or urethra)
        • degree of obstruction
          • partial
          • complete
    • Postrenal Acute Renal Failure
    • Postrenal Acute Renal Failure
    • Postrenal Acute Renal Failure
    • Pathophysiology of Renal Failure in Obstructive Uropathy
      • Early
        • Increased intratubular pressure
        • Initial increase followed by decrease in renal plasma flow
      • Late
        • Normal intratubular pressure
        • Marked decrease in renal plasma flow
    • Etiologies of Postrenal Acute Renal Failure
      • Upper tract obstruction
        • Intrinsic
          • nephrolithiasis
          • papillary necrosis
          • blood clot
          • transitional cell cancer
        • Extrinsic
          • retroperitoneal or pelvic malignancy
          • retroperitoneal fibrosis
          • endometriosis
          • abdominal aortic aneurysm
      • Lower tract obstruction
          • benign prostatic hypertrophy
          • prostate cancer
          • transitional cell cancer
          • urethral stricture
          • bladder stones
          • blood clot
          • neurogenic bladder
    • Postrenal Acute Renal Failure: Clinical Presentation
      • History
        • Symptoms of bladder outlet obstruction
          • urinary frequency
          • urgency
          • intermittency
          • hesitancy
          • nocturia
          • incomplete voiding
    • Postrenal Acute Renal Failure: Clinical Presentation
      • History
        • Changes in urine volume
          • anuria
          • polyuria
          • fluctuating urine volume
        • Flank pain
        • Hematuria
        • History of pelvic malignancy
    • Postrenal Acute Renal Failure: Clinical Presentation
      • Physical Examination
        • Suprapubic mass
        • Prostatic enlargement
        • Pelvic masses
        • Adenopathy
    • Postrenal Acute Renal Failure: Clinical Evaluation
      • Diagnostic studies
        • BUN: Creatinine ratio > 20:1
        • Unremarkable urine sediment
        • Variable urine chemistries
    • Postrenal Acute Renal Failure: Clinical Evaluation
      • Diagnostic studies
        • Post-void residual bladder volume
          • > 100 mL consistent with voiding dysfunction
        • Radiologic studies
          • Ultrasound
          • CT scan
          • Nuclear medicine
          • Retrograde pyelography
          • Antegrade nephrostograms
    • Renal Ultrasound - Hydronephrosis
    • Treatment of Postrenal Acute Renal Failure
      • Relief of obstruction
        • Lower tract obstruction
          • bladder catheter
        • Upper tract obstruction
          • ureteral stents
          • percutaneous nephrostomies
      • Recovery of renal function dependent upon duration of obstruction
      • Risk of post-obstructive diuresis
    • Intrinsic Acute Renal Failure
      • Acute tubular necrosis (ATN)
      • Acute interstitial nephritis (AIN)
      • Acute glomerulonephritis (AGN)
      • Acute vascular syndromes
      • Intratubular obstruction
    • Acute Tubular Necrosis
    • Acute Tubular Necrosis
      • Ischemic
          • prolonged prerenal azotemia
          • hypotension
          • hypovolemic shock
          • cardiopulmonary arrest
          • cardiopulmonary bypass
      • Sepsis
      • Nephrotoxic
        • drug-induced
          • radiocontrast agents
          • aminoglycosides
          • amphotericin B
          • cisplatinum
          • acetaminophen
        • pigment nephropathy
          • hemoglobin
          • myoglobin
    • Pathophysiology of ATN: Tubular Epithelial Cell Injury and Repair Loss of polarity Normal Epithelium Migration , Dedifferentiation of Viable Cells Differentiation & Reestablishment of polarity Sloughing of viable and dead cells with luminal obstruction Ischemia/ Reperfusion Apoptosis Necrosis Cell death Adhesion molecules Na + /K + -ATPase Proliferation
    • Pathophysiology of Acute Tubular Necrosis
      • Mechanisms of decreased renal function
        • Vasoconstriction
        • Tubular obstruction by sloughed debris
        • Backleak of glomerular filtrate across denuded tubular basement membrane
    • Phases of Ischemic ATN Prerenal Initiation Extension Maintenance Recovery GFR Time
    • Pathophysiology of ATN Ischemia Endothelial Injury Capillary Obstruction & Continued Ischemia Inflammation Tubular Injury Disruption of Cytoskeleton Loss of Cell Polarity Desquamation of Cells Tubular Obstruction & Backleak Apoptosis & Necrosis Activation of Vasoconstrictors Impaired Vasodilation Increased Leukocyte Adhesion
    • Acute Tubular Necrosis: Clinical Presentation
      • History
        • Acute illness
        • Exposure to nephrotoxins
        • Episodes of hypotension
      • Physical examination
        • Hemodynamic status
        • Volume status
        • Features of associated illness
      • Laboratory data
        • BUN:Creatinine ratio < 10:1
        • Evidence of toxin exposure
    • Acute Tubular Necrosis: Clinical Presentation
      • Urine indices
        • Urine volume
          • may be oliguric or non-oliguric
        • Isosthenuric urine concentration
          • U Osm  300 mmol/L
          • specific gravity  1.010
        • Evidence of renal sodium wasting
          • U Na > 40 mmol/L
          • FE Na > 0.02
        • Urine sediment
          • tubular epithelial cells
          • granular casts
    • Acute Tubular Necrosis: Clinical Presentation
    • Acute Tubular Necrosis: Treatment
      • Supportive therapy
      • No specific pharmacologic treatments
      • Acute dialysis for:
        • volume overload
        • metabolic acidosis
        • hyperkalemia
        • uremic syndrome
          • pericarditis
          • encephalopathy
        • azotemia
    • Prognosis of Acute Tubular Necrosis
      • Mortality dependent upon comorbid conditions
        • overall mortality ~ 50%
      • Recovery of renal function seen in ~ 90% of patients who survive - although not necessarily back to prior baseline renal function
    • Mortality in Acute Tubular Necrosis Chertow et al: Arch Int Med 1995; 155:1505-1511 Number of Failed Non-Respiratory Organ Systems
    • Effect of Contrast Nephropathy on Mortality Levy et al: JAMA 1996; 275:1489-1494
    • Acute Interstitial Nephritis
      • Acute renal failure due to lymphocytic infiltration of the interstitium
      • Classic triad of
        • fever
        • rash
        • eosinophilia
    • Acute Interstitial Nephritis
    • Acute Interstitial Nephritis
      • Drug-induced
        • penicillins
        • cephalosporins
        • sulfonamides
        • rifampin
        • phenytoin
        • furosemide
        • NSAIDs
      • Malignancy
      • Idiopathic
      • Infection-related
        • bacterial
        • viral
        • rickettsial
        • tuberculosis
      • Systemic diseases
        • SLE
        • sarcoidosis
        • Sjögren’s syndrome
        • tubulointerstitial nephritis and uveitis
    • Acute Interstitial Nephritis: Clinical Presentation
      • History
        • preceding illness or drug exposure
      • Physical examination
        • fever
        • rash
      • Laboratory Findings
        • eosinophilia
    • Acute Interstitial Nephritis: Clinical Presentation
      • Urine findings
        • non-nephrotic protinuria
        • hematuria
        • pyuria
        • WBC casts
        • eosinophiluria
    • Acute Interstitial Nephritis: Clinical Presentation
    • Acute Interstitial Nephritis: Clinical Presentation
    • Acute Interstitial Nephritis: Treatment
      • Discontinue offending drug
      • Treat underlying infection
      • Treat systemic illness
      • Glucocorticoid therapy may be used in patients who fail to respond to more conservative therapy
    • Acute Glomerulonephritis
      • Nephritic presentation
        • proteinuria
          • may be in nephrotic range (> 3 g/day)
        • hematuria
        • RBC casts
      • Diagnosis usually requires renal biopsy
    • Acute Glomerulonephritis
    • Acute Glomerulonephritis
      • Etiologies
        • poststreptococcal glomerulonephritis
        • postinfectious glomerulonephritis
        • endocarditis-associated glomerulonephritis
        • systemic vasculitis
        • thrombotic microangiopathy
          • hemolytic-uremic syndrome
          • thrombotic thrombocytopenic purpura
        • rapidly progressive glomerulonephritis
    • Acute Vascular Syndromes
      • Renal artery thromboembolism
      • Renal artery dissection
      • Renal vein thrombosis
      • Atheroembolic disease
    • Atheroembolic Disease
    • Intratubular Obstruction
      • Intratubular crystal deposition
        • tumor lysis syndrome
          • acute urate nephropathy
        • ethylene glycol toxicity
          • calcium oxylate deposition
      • Intratubular protein deposition
        • multiple myeloma
          • -Bence-Jones protein deposition
    • Differential Diagnosis of Acute Renal Failure
      • Prerenal ARF
      • Postrenal ARF
      • Intrinsic ARF
        • acute tubular necrosis
        • acute interstitial nephritis
        • acute glomerulonephritis
        • acute vascular syndromes
        • intratubular obstruction
    • Acute Renal Failure: Diagnostic Evaluation
      • Evaluate for prerenal causes
        • clinical exam
          • blood pressure
          • orthostasis
        • central venous pressures and cardiac output
        • intake/output record
        • urine sediment
        • urine sodium
          • U Na < 20 mmol/L
        • therapeutic trial of volume replacement
        • skin turgor
        • mucosal membrane hydration
        • FE Na < 0.01
    • Acute Renal Failure: Diagnostic Evaluation
      • Evaluate for postrenal causes
        • bladder catheterization
        • renal ultrasound
    • Acute Renal Failure: Diagnostic Evaluation
      • Evaluation for intrinsic ARF
        • clinical history
          • medications
          • hypotension
        • physical exam
        • urinalysis
          • crystals
          • paraproteins
        • radiocontrast agents
        • sepsis
        • cells
        • casts
    • Diagnostic Evaluation of ARF Muddy brown casts; tubular epithelial cells > 2% >40 <10:1 ATN Normal or RBC’s variable >20 variable Vascular RBC’s, RBC casts <1% <40 variable AGN WBC’s WBC casts, RBC’s, eosinophils >1% >20 <20:1 AIN Intrinsic Normal or RBC’s variable >20 >20:1 Postrenal Normal < 1% <20 >20:1 Prerenal Urine Sediment FE Na U Na (mEq/L) BUN:Cr Form of ARF
    • Acute Renal Failure: Management
      • Prerenal ARF
        • volume repletion
        • inotropic support
        • discontinue diuretics
      • Postrenal ARF
        • bladder catheterization
        • percutaneous nephrostomy or ureteral stents
        • fluid management during post-obstructive diuresis
    • Acute Renal Failure: Management
      • Intrinsic ARF
        • General supportive care
          • fluid management
          • diuretics
          • bicarbonate supplementation
          • potassium
          • phosphate
          • drug dosing
          • nutrition
    • Acute Renal Failure: Management
      • Indications for dialysis
        • volume overload
        • metabolic acidosis
        • hyperkalemia
        • uremic syndrome
          • pericarditis
          • encephalopathy
        • azotemia