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Acute Renal Failure Paul M. Palevsky, M.D. Professor of Medicine Chief, Renal Section VA Pittsburgh Healthcare System
Acute Renal Failure <ul><li>Definition </li></ul><ul><ul><li>The loss of renal function (measured as GFR) over hours to da...
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 ...
Acute Renal Failure <ul><li>Definitions </li></ul><ul><ul><li>Azotemia - the accumulation of nitrogenous wastes </li></ul>...
Manifestations of ARF <ul><li>Azotemia progressing to uremia </li></ul><ul><li>Hyperkalemia </li></ul><ul><li>Metabolic ac...
Differential Diagnosis of Azotemia <ul><li>Etiologies of acute elevations of BUN </li></ul><ul><ul><li>Acute renal failure...
Differential Diagnosis of Azotemia <ul><li>Etiologies of acute elevations of creatinine </li></ul><ul><ul><li>Acute renal ...
Classification of the Etiologies of Acute Renal Failure Acute Renal Failure Acute Tubular Necrosis Acute Interstitial Neph...
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 + + + ...
Prerenal Acute Renal Failure <ul><li>Volume Depletion </li></ul><ul><li>Decreased effective blood volume </li></ul><ul><ul...
Prerenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>volume loss (e.g., diarrhea, acu...
Prerenal Acute Renal Failure: Clinical Presentation <ul><li>Physical Examination </li></ul><ul><ul><li>Blood pressure and ...
Prerenal Acute Renal Failure:  Clinical Presentation <ul><li>BUN:Creatinine ratio </li></ul><ul><ul><li>> 20:1 </li></ul><...
Fractional Excretion of Sodium FE Na  =   Filtered Sodium Excreted Sodium FE Na  =   P Na  x GFR U Na  x V FE Na  =   U Cr...
Fractional Excretion of Sodium <ul><li>Etiologies of a fractional excretion of sodium < 0.01 </li></ul><ul><ul><li>normal ...
Treatment of  Prerenal Acute Renal Failure <ul><li>Correction of volume deficits </li></ul><ul><li>Discontinuation of anta...
Postrenal Acute Renal Failure <ul><li>Urinary tract obstruction </li></ul><ul><ul><li>level of obstruction </li></ul></ul>...
Postrenal Acute Renal Failure
Postrenal Acute Renal Failure
Postrenal Acute Renal Failure
Pathophysiology of Renal Failure in Obstructive Uropathy <ul><li>Early </li></ul><ul><ul><li>Increased intratubular pressu...
Etiologies of Postrenal  Acute Renal Failure <ul><li>Upper tract obstruction </li></ul><ul><ul><li>Intrinsic </li></ul></u...
Postrenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Symptoms of bladder outlet obst...
Postrenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Changes in urine volume </li></...
Postrenal Acute Renal Failure: Clinical Presentation <ul><li>Physical Examination </li></ul><ul><ul><li>Suprapubic mass </...
Postrenal Acute Renal Failure: Clinical Evaluation <ul><li>Diagnostic studies </li></ul><ul><ul><li>BUN: Creatinine ratio ...
Postrenal Acute Renal Failure: Clinical Evaluation <ul><li>Diagnostic studies </li></ul><ul><ul><li>Post-void residual bla...
Renal Ultrasound - Hydronephrosis
Treatment of  Postrenal Acute Renal Failure <ul><li>Relief of obstruction </li></ul><ul><ul><li>Lower tract obstruction </...
Intrinsic Acute Renal Failure <ul><li>Acute tubular necrosis (ATN) </li></ul><ul><li>Acute interstitial nephritis (AIN) </...
Acute Tubular Necrosis
Acute Tubular Necrosis <ul><li>Ischemic </li></ul><ul><ul><ul><li>prolonged prerenal azotemia </li></ul></ul></ul><ul><ul>...
Pathophysiology of ATN: Tubular Epithelial Cell Injury and Repair Loss of polarity Normal Epithelium Migration , Dediffere...
Pathophysiology of  Acute Tubular Necrosis <ul><li>Mechanisms of decreased renal function </li></ul><ul><ul><li>Vasoconstr...
Phases of Ischemic ATN Prerenal Initiation Extension Maintenance Recovery GFR Time
Pathophysiology of ATN Ischemia Endothelial Injury Capillary Obstruction & Continued Ischemia Inflammation Tubular Injury ...
Acute Tubular Necrosis:  Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Acute illness </li></ul></ul><ul><ul>...
Acute Tubular Necrosis:  Clinical Presentation <ul><li>Urine indices </li></ul><ul><ul><li>Urine volume </li></ul></ul><ul...
Acute Tubular Necrosis:  Clinical Presentation
Acute Tubular Necrosis: Treatment <ul><li>Supportive therapy </li></ul><ul><li>No specific pharmacologic treatments </li><...
Prognosis of Acute Tubular Necrosis <ul><li>Mortality dependent upon comorbid conditions </li></ul><ul><ul><li>overall mor...
Mortality in Acute Tubular Necrosis Chertow et al: Arch Int Med 1995; 155:1505-1511 Number of Failed Non-Respiratory Organ...
Effect of Contrast Nephropathy on Mortality Levy et al: JAMA 1996; 275:1489-1494
Acute Interstitial Nephritis <ul><li>Acute renal failure due to lymphocytic infiltration of the interstitium </li></ul><ul...
Acute Interstitial Nephritis
Acute Interstitial Nephritis <ul><li>Drug-induced </li></ul><ul><ul><li>penicillins </li></ul></ul><ul><ul><li>cephalospor...
Acute Interstitial Nephritis: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>preceding illness or drug exposu...
Acute Interstitial Nephritis: Clinical Presentation <ul><li>Urine findings </li></ul><ul><ul><li>non-nephrotic protinuria ...
Acute Interstitial Nephritis: Clinical Presentation
Acute Interstitial Nephritis: Clinical Presentation
Acute Interstitial Nephritis: Treatment <ul><li>Discontinue offending drug </li></ul><ul><li>Treat underlying infection </...
Acute Glomerulonephritis <ul><li>Nephritic presentation </li></ul><ul><ul><li>proteinuria </li></ul></ul><ul><ul><ul><li>m...
Acute Glomerulonephritis
Acute Glomerulonephritis <ul><li>Etiologies </li></ul><ul><ul><li>poststreptococcal glomerulonephritis </li></ul></ul><ul>...
Acute Vascular Syndromes <ul><li>Renal artery thromboembolism </li></ul><ul><li>Renal artery dissection </li></ul><ul><li>...
Atheroembolic Disease
Intratubular Obstruction <ul><li>Intratubular crystal deposition </li></ul><ul><ul><li>tumor lysis syndrome </li></ul></ul...
Differential Diagnosis of  Acute Renal Failure <ul><li>Prerenal ARF </li></ul><ul><li>Postrenal ARF </li></ul><ul><li>Intr...
Acute Renal Failure:  Diagnostic Evaluation <ul><li>Evaluate for prerenal causes </li></ul><ul><ul><li>clinical exam </li>...
Acute Renal Failure: Diagnostic Evaluation <ul><li>Evaluate for postrenal causes </li></ul><ul><ul><li>bladder catheteriza...
Acute Renal Failure: Diagnostic Evaluation <ul><li>Evaluation for intrinsic ARF </li></ul><ul><ul><li>clinical history </l...
Diagnostic Evaluation of ARF Muddy brown casts; tubular epithelial cells > 2% >40 <10:1 ATN Normal or RBC’s variable >20 v...
Acute Renal Failure: Management <ul><li>Prerenal ARF </li></ul><ul><ul><li>volume repletion </li></ul></ul><ul><ul><li>ino...
Acute Renal Failure: Management <ul><li>Intrinsic ARF </li></ul><ul><ul><li>General supportive care </li></ul></ul><ul><ul...
Acute Renal Failure: Management <ul><li>Indications for dialysis </li></ul><ul><ul><li>volume overload  </li></ul></ul><ul...
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10 Palevsky Acute Renal Failure

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Transcript of "10 Palevsky Acute Renal Failure"

  1. 1. Acute Renal Failure Paul M. Palevsky, M.D. Professor of Medicine Chief, Renal Section VA Pittsburgh Healthcare System
  2. 2. Acute Renal Failure <ul><li>Definition </li></ul><ul><ul><li>The loss of renal function (measured as GFR) over hours to days </li></ul></ul><ul><ul><li>Expressed clinically as the retention of nitrogenous waste products in the blood </li></ul></ul>
  3. 3. 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)
  4. 4. Acute Renal Failure <ul><li>Definitions </li></ul><ul><ul><li>Azotemia - the accumulation of nitrogenous wastes </li></ul></ul><ul><ul><li>Uremia - symptomatic renal failure </li></ul></ul><ul><ul><li>Oliguria - urine output < 400-500 mL/24 hours </li></ul></ul><ul><ul><li>Anuria - urine output < 100 mL/24 hours </li></ul></ul>
  5. 5. Manifestations of ARF <ul><li>Azotemia progressing to uremia </li></ul><ul><li>Hyperkalemia </li></ul><ul><li>Metabolic acidosis </li></ul><ul><li>Volume overload </li></ul><ul><li>Hyperphosphatemia </li></ul><ul><li>Accumulation and toxicity of medications excreted by the kidney </li></ul>
  6. 6. Differential Diagnosis of Azotemia <ul><li>Etiologies of acute elevations of BUN </li></ul><ul><ul><li>Acute renal failure </li></ul></ul><ul><ul><li>Protein loading </li></ul></ul><ul><ul><li>GI bleeding </li></ul></ul><ul><ul><li>Catabolic steroids </li></ul></ul><ul><ul><li>Tetracycline antibiotics </li></ul></ul>
  7. 7. Differential Diagnosis of Azotemia <ul><li>Etiologies of acute elevations of creatinine </li></ul><ul><ul><li>Acute renal failure </li></ul></ul><ul><ul><li>Medications that block creatinine secretion </li></ul></ul><ul><ul><ul><li>cimetidine </li></ul></ul></ul><ul><ul><ul><li>trimethoprim </li></ul></ul></ul><ul><ul><li>Substances that interfere with creatinine assay </li></ul></ul><ul><ul><ul><li>cefoxitin </li></ul></ul></ul><ul><ul><ul><li>flucytosine </li></ul></ul></ul><ul><ul><ul><li>acetoacetate </li></ul></ul></ul>
  8. 8. 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
  9. 9. Physiologic Response to Volume Depletion Na Reabsorption AII AII PG RPF GFR P GC FF Urea Reabsorption
  10. 10. Prerenal Acute Renal Failure Na Reabsorption AII AII PG RPF GFR P GC FF Urea Reabsorption
  11. 11. Pathogenesis of Prerenal Azotemia Renal Vasoconstriction Decreased GFR Angiotensin II Adrenergic nerves Vasopressin + + + Nitric oxide Prostaglandins - - Volume Depletion Congestive Heart Failure Liver Failure Sepsis
  12. 12. Prerenal Acute Renal Failure <ul><li>Volume Depletion </li></ul><ul><li>Decreased effective blood volume </li></ul><ul><ul><li>congestive heart failure </li></ul></ul><ul><ul><li>cirrhosis </li></ul></ul><ul><ul><li>nephrotic syndrome </li></ul></ul><ul><ul><li>sepsis </li></ul></ul><ul><li>Renal vasoconstriction </li></ul><ul><ul><li>hepatorenal syndrome </li></ul></ul><ul><ul><li>hypercalcemia </li></ul></ul><ul><ul><li>nonsteroidal anti-inflammatory drugs </li></ul></ul>
  13. 13. Prerenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>volume loss (e.g., diarrhea, acute blood loss) </li></ul></ul><ul><ul><li>heart disease </li></ul></ul><ul><ul><li>liver disease </li></ul></ul><ul><ul><li>evidence of infection </li></ul></ul><ul><ul><li>diuretic use </li></ul></ul><ul><ul><li>thirst </li></ul></ul><ul><ul><li>orthostatic symptoms </li></ul></ul>
  14. 14. Prerenal Acute Renal Failure: Clinical Presentation <ul><li>Physical Examination </li></ul><ul><ul><li>Blood pressure and pulse </li></ul></ul><ul><ul><li>Orthostatic changes in blood pressure </li></ul></ul><ul><ul><li>Skin turgor </li></ul></ul><ul><ul><li>Dryness of mucous membranes and axillae </li></ul></ul><ul><ul><li>Neck veins </li></ul></ul><ul><ul><li>Cardiopulmonary exam </li></ul></ul><ul><ul><li>Peripheral edema </li></ul></ul>
  15. 15. Prerenal Acute Renal Failure: Clinical Presentation <ul><li>BUN:Creatinine ratio </li></ul><ul><ul><li>> 20:1 </li></ul></ul><ul><li>Urine indices </li></ul><ul><ul><li>Oliguria </li></ul></ul><ul><ul><ul><li>usually < 500 mL/24 hours; but may be non-oliguric </li></ul></ul></ul><ul><ul><li>Elevated urine concentration </li></ul></ul><ul><ul><ul><li>U Osm > 700 mmol/L </li></ul></ul></ul><ul><ul><ul><li>specific gravity > 1.020 </li></ul></ul></ul><ul><ul><li>Evidence of high renal sodium avidity </li></ul></ul><ul><ul><ul><li>U Na < 20 mmol/L </li></ul></ul></ul><ul><ul><ul><li>FE Na < 0.01 </li></ul></ul></ul><ul><ul><li>Inactive urine sediment </li></ul></ul>
  16. 16. 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
  17. 17. Fractional Excretion of Sodium <ul><li>Etiologies of a fractional excretion of sodium < 0.01 </li></ul><ul><ul><li>normal renal function </li></ul></ul><ul><ul><li>prerenal azotemia </li></ul></ul><ul><ul><li>hepatorenal syndrome </li></ul></ul><ul><ul><li>early obstructive uropathy </li></ul></ul><ul><ul><li>contrast nephropathy </li></ul></ul><ul><ul><li>rhabdomyolysis </li></ul></ul><ul><ul><li>acute glomerulonephritis </li></ul></ul>
  18. 18. Treatment of Prerenal Acute Renal Failure <ul><li>Correction of volume deficits </li></ul><ul><li>Discontinuation of antagonizing medications </li></ul><ul><ul><li>NSAIDs/COX-2 inhibitors </li></ul></ul><ul><ul><li>Diuretics </li></ul></ul><ul><li>Optimization of cardiac function </li></ul>
  19. 19. Postrenal Acute Renal Failure <ul><li>Urinary tract obstruction </li></ul><ul><ul><li>level of obstruction </li></ul></ul><ul><ul><ul><li>upper tract (ureters) </li></ul></ul></ul><ul><ul><ul><li>lower tract (bladder outlet or urethra) </li></ul></ul></ul><ul><ul><li>degree of obstruction </li></ul></ul><ul><ul><ul><li>partial </li></ul></ul></ul><ul><ul><ul><li>complete </li></ul></ul></ul>
  20. 20. Postrenal Acute Renal Failure
  21. 21. Postrenal Acute Renal Failure
  22. 22. Postrenal Acute Renal Failure
  23. 23. Pathophysiology of Renal Failure in Obstructive Uropathy <ul><li>Early </li></ul><ul><ul><li>Increased intratubular pressure </li></ul></ul><ul><ul><li>Initial increase followed by decrease in renal plasma flow </li></ul></ul><ul><li>Late </li></ul><ul><ul><li>Normal intratubular pressure </li></ul></ul><ul><ul><li>Marked decrease in renal plasma flow </li></ul></ul>
  24. 24. Etiologies of Postrenal Acute Renal Failure <ul><li>Upper tract obstruction </li></ul><ul><ul><li>Intrinsic </li></ul></ul><ul><ul><ul><li>nephrolithiasis </li></ul></ul></ul><ul><ul><ul><li>papillary necrosis </li></ul></ul></ul><ul><ul><ul><li>blood clot </li></ul></ul></ul><ul><ul><ul><li>transitional cell cancer </li></ul></ul></ul><ul><ul><li>Extrinsic </li></ul></ul><ul><ul><ul><li>retroperitoneal or pelvic malignancy </li></ul></ul></ul><ul><ul><ul><li>retroperitoneal fibrosis </li></ul></ul></ul><ul><ul><ul><li>endometriosis </li></ul></ul></ul><ul><ul><ul><li>abdominal aortic aneurysm </li></ul></ul></ul><ul><li>Lower tract obstruction </li></ul><ul><ul><ul><li>benign prostatic hypertrophy </li></ul></ul></ul><ul><ul><ul><li>prostate cancer </li></ul></ul></ul><ul><ul><ul><li>transitional cell cancer </li></ul></ul></ul><ul><ul><ul><li>urethral stricture </li></ul></ul></ul><ul><ul><ul><li>bladder stones </li></ul></ul></ul><ul><ul><ul><li>blood clot </li></ul></ul></ul><ul><ul><ul><li>neurogenic bladder </li></ul></ul></ul>
  25. 25. Postrenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Symptoms of bladder outlet obstruction </li></ul></ul><ul><ul><ul><li>urinary frequency </li></ul></ul></ul><ul><ul><ul><li>urgency </li></ul></ul></ul><ul><ul><ul><li>intermittency </li></ul></ul></ul><ul><ul><ul><li>hesitancy </li></ul></ul></ul><ul><ul><ul><li>nocturia </li></ul></ul></ul><ul><ul><ul><li>incomplete voiding </li></ul></ul></ul>
  26. 26. Postrenal Acute Renal Failure: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Changes in urine volume </li></ul></ul><ul><ul><ul><li>anuria </li></ul></ul></ul><ul><ul><ul><li>polyuria </li></ul></ul></ul><ul><ul><ul><li>fluctuating urine volume </li></ul></ul></ul><ul><ul><li>Flank pain </li></ul></ul><ul><ul><li>Hematuria </li></ul></ul><ul><ul><li>History of pelvic malignancy </li></ul></ul>
  27. 27. Postrenal Acute Renal Failure: Clinical Presentation <ul><li>Physical Examination </li></ul><ul><ul><li>Suprapubic mass </li></ul></ul><ul><ul><li>Prostatic enlargement </li></ul></ul><ul><ul><li>Pelvic masses </li></ul></ul><ul><ul><li>Adenopathy </li></ul></ul>
  28. 28. Postrenal Acute Renal Failure: Clinical Evaluation <ul><li>Diagnostic studies </li></ul><ul><ul><li>BUN: Creatinine ratio > 20:1 </li></ul></ul><ul><ul><li>Unremarkable urine sediment </li></ul></ul><ul><ul><li>Variable urine chemistries </li></ul></ul>
  29. 29. Postrenal Acute Renal Failure: Clinical Evaluation <ul><li>Diagnostic studies </li></ul><ul><ul><li>Post-void residual bladder volume </li></ul></ul><ul><ul><ul><li>> 100 mL consistent with voiding dysfunction </li></ul></ul></ul><ul><ul><li>Radiologic studies </li></ul></ul><ul><ul><ul><li>Ultrasound </li></ul></ul></ul><ul><ul><ul><li>CT scan </li></ul></ul></ul><ul><ul><ul><li>Nuclear medicine </li></ul></ul></ul><ul><ul><ul><li>Retrograde pyelography </li></ul></ul></ul><ul><ul><ul><li>Antegrade nephrostograms </li></ul></ul></ul>
  30. 30. Renal Ultrasound - Hydronephrosis
  31. 31. Treatment of Postrenal Acute Renal Failure <ul><li>Relief of obstruction </li></ul><ul><ul><li>Lower tract obstruction </li></ul></ul><ul><ul><ul><li>bladder catheter </li></ul></ul></ul><ul><ul><li>Upper tract obstruction </li></ul></ul><ul><ul><ul><li>ureteral stents </li></ul></ul></ul><ul><ul><ul><li>percutaneous nephrostomies </li></ul></ul></ul><ul><li>Recovery of renal function dependent upon duration of obstruction </li></ul><ul><li>Risk of post-obstructive diuresis </li></ul>
  32. 32. Intrinsic Acute Renal Failure <ul><li>Acute tubular necrosis (ATN) </li></ul><ul><li>Acute interstitial nephritis (AIN) </li></ul><ul><li>Acute glomerulonephritis (AGN) </li></ul><ul><li>Acute vascular syndromes </li></ul><ul><li>Intratubular obstruction </li></ul>
  33. 33. Acute Tubular Necrosis
  34. 34. Acute Tubular Necrosis <ul><li>Ischemic </li></ul><ul><ul><ul><li>prolonged prerenal azotemia </li></ul></ul></ul><ul><ul><ul><li>hypotension </li></ul></ul></ul><ul><ul><ul><li>hypovolemic shock </li></ul></ul></ul><ul><ul><ul><li>cardiopulmonary arrest </li></ul></ul></ul><ul><ul><ul><li>cardiopulmonary bypass </li></ul></ul></ul><ul><li>Sepsis </li></ul><ul><li>Nephrotoxic </li></ul><ul><ul><li>drug-induced </li></ul></ul><ul><ul><ul><li>radiocontrast agents </li></ul></ul></ul><ul><ul><ul><li>aminoglycosides </li></ul></ul></ul><ul><ul><ul><li>amphotericin B </li></ul></ul></ul><ul><ul><ul><li>cisplatinum </li></ul></ul></ul><ul><ul><ul><li>acetaminophen </li></ul></ul></ul><ul><ul><li>pigment nephropathy </li></ul></ul><ul><ul><ul><li>hemoglobin </li></ul></ul></ul><ul><ul><ul><li>myoglobin </li></ul></ul></ul>
  35. 35. 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
  36. 36. Pathophysiology of Acute Tubular Necrosis <ul><li>Mechanisms of decreased renal function </li></ul><ul><ul><li>Vasoconstriction </li></ul></ul><ul><ul><li>Tubular obstruction by sloughed debris </li></ul></ul><ul><ul><li>Backleak of glomerular filtrate across denuded tubular basement membrane </li></ul></ul>
  37. 37. Phases of Ischemic ATN Prerenal Initiation Extension Maintenance Recovery GFR Time
  38. 38. 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
  39. 39. Acute Tubular Necrosis: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>Acute illness </li></ul></ul><ul><ul><li>Exposure to nephrotoxins </li></ul></ul><ul><ul><li>Episodes of hypotension </li></ul></ul><ul><li>Physical examination </li></ul><ul><ul><li>Hemodynamic status </li></ul></ul><ul><ul><li>Volume status </li></ul></ul><ul><ul><li>Features of associated illness </li></ul></ul><ul><li>Laboratory data </li></ul><ul><ul><li>BUN:Creatinine ratio < 10:1 </li></ul></ul><ul><ul><li>Evidence of toxin exposure </li></ul></ul>
  40. 40. Acute Tubular Necrosis: Clinical Presentation <ul><li>Urine indices </li></ul><ul><ul><li>Urine volume </li></ul></ul><ul><ul><ul><li>may be oliguric or non-oliguric </li></ul></ul></ul><ul><ul><li>Isosthenuric urine concentration </li></ul></ul><ul><ul><ul><li>U Osm  300 mmol/L </li></ul></ul></ul><ul><ul><ul><li>specific gravity  1.010 </li></ul></ul></ul><ul><ul><li>Evidence of renal sodium wasting </li></ul></ul><ul><ul><ul><li>U Na > 40 mmol/L </li></ul></ul></ul><ul><ul><ul><li>FE Na > 0.02 </li></ul></ul></ul><ul><ul><li>Urine sediment </li></ul></ul><ul><ul><ul><li>tubular epithelial cells </li></ul></ul></ul><ul><ul><ul><li>granular casts </li></ul></ul></ul>
  41. 41. Acute Tubular Necrosis: Clinical Presentation
  42. 42. Acute Tubular Necrosis: Treatment <ul><li>Supportive therapy </li></ul><ul><li>No specific pharmacologic treatments </li></ul><ul><li>Acute dialysis for: </li></ul><ul><ul><li>volume overload </li></ul></ul><ul><ul><li>metabolic acidosis </li></ul></ul><ul><ul><li>hyperkalemia </li></ul></ul><ul><ul><li>uremic syndrome </li></ul></ul><ul><ul><ul><li>pericarditis </li></ul></ul></ul><ul><ul><ul><li>encephalopathy </li></ul></ul></ul><ul><ul><li>azotemia </li></ul></ul>
  43. 43. Prognosis of Acute Tubular Necrosis <ul><li>Mortality dependent upon comorbid conditions </li></ul><ul><ul><li>overall mortality ~ 50% </li></ul></ul><ul><li>Recovery of renal function seen in ~ 90% of patients who survive - although not necessarily back to prior baseline renal function </li></ul>
  44. 44. Mortality in Acute Tubular Necrosis Chertow et al: Arch Int Med 1995; 155:1505-1511 Number of Failed Non-Respiratory Organ Systems
  45. 45. Effect of Contrast Nephropathy on Mortality Levy et al: JAMA 1996; 275:1489-1494
  46. 46. Acute Interstitial Nephritis <ul><li>Acute renal failure due to lymphocytic infiltration of the interstitium </li></ul><ul><li>Classic triad of </li></ul><ul><ul><li>fever </li></ul></ul><ul><ul><li>rash </li></ul></ul><ul><ul><li>eosinophilia </li></ul></ul>
  47. 47. Acute Interstitial Nephritis
  48. 48. Acute Interstitial Nephritis <ul><li>Drug-induced </li></ul><ul><ul><li>penicillins </li></ul></ul><ul><ul><li>cephalosporins </li></ul></ul><ul><ul><li>sulfonamides </li></ul></ul><ul><ul><li>rifampin </li></ul></ul><ul><ul><li>phenytoin </li></ul></ul><ul><ul><li>furosemide </li></ul></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><li>Malignancy </li></ul><ul><li>Idiopathic </li></ul><ul><li>Infection-related </li></ul><ul><ul><li>bacterial </li></ul></ul><ul><ul><li>viral </li></ul></ul><ul><ul><li>rickettsial </li></ul></ul><ul><ul><li>tuberculosis </li></ul></ul><ul><li>Systemic diseases </li></ul><ul><ul><li>SLE </li></ul></ul><ul><ul><li>sarcoidosis </li></ul></ul><ul><ul><li>Sjögren’s syndrome </li></ul></ul><ul><ul><li>tubulointerstitial nephritis and uveitis </li></ul></ul>
  49. 49. Acute Interstitial Nephritis: Clinical Presentation <ul><li>History </li></ul><ul><ul><li>preceding illness or drug exposure </li></ul></ul><ul><li>Physical examination </li></ul><ul><ul><li>fever </li></ul></ul><ul><ul><li>rash </li></ul></ul><ul><li>Laboratory Findings </li></ul><ul><ul><li>eosinophilia </li></ul></ul>
  50. 50. Acute Interstitial Nephritis: Clinical Presentation <ul><li>Urine findings </li></ul><ul><ul><li>non-nephrotic protinuria </li></ul></ul><ul><ul><li>hematuria </li></ul></ul><ul><ul><li>pyuria </li></ul></ul><ul><ul><li>WBC casts </li></ul></ul><ul><ul><li>eosinophiluria </li></ul></ul>
  51. 51. Acute Interstitial Nephritis: Clinical Presentation
  52. 52. Acute Interstitial Nephritis: Clinical Presentation
  53. 53. Acute Interstitial Nephritis: Treatment <ul><li>Discontinue offending drug </li></ul><ul><li>Treat underlying infection </li></ul><ul><li>Treat systemic illness </li></ul><ul><li>Glucocorticoid therapy may be used in patients who fail to respond to more conservative therapy </li></ul>
  54. 54. Acute Glomerulonephritis <ul><li>Nephritic presentation </li></ul><ul><ul><li>proteinuria </li></ul></ul><ul><ul><ul><li>may be in nephrotic range (> 3 g/day) </li></ul></ul></ul><ul><ul><li>hematuria </li></ul></ul><ul><ul><li>RBC casts </li></ul></ul><ul><li>Diagnosis usually requires renal biopsy </li></ul>
  55. 55. Acute Glomerulonephritis
  56. 56. Acute Glomerulonephritis <ul><li>Etiologies </li></ul><ul><ul><li>poststreptococcal glomerulonephritis </li></ul></ul><ul><ul><li>postinfectious glomerulonephritis </li></ul></ul><ul><ul><li>endocarditis-associated glomerulonephritis </li></ul></ul><ul><ul><li>systemic vasculitis </li></ul></ul><ul><ul><li>thrombotic microangiopathy </li></ul></ul><ul><ul><ul><li>hemolytic-uremic syndrome </li></ul></ul></ul><ul><ul><ul><li>thrombotic thrombocytopenic purpura </li></ul></ul></ul><ul><ul><li>rapidly progressive glomerulonephritis </li></ul></ul>
  57. 57. Acute Vascular Syndromes <ul><li>Renal artery thromboembolism </li></ul><ul><li>Renal artery dissection </li></ul><ul><li>Renal vein thrombosis </li></ul><ul><li>Atheroembolic disease </li></ul>
  58. 58. Atheroembolic Disease
  59. 59. Intratubular Obstruction <ul><li>Intratubular crystal deposition </li></ul><ul><ul><li>tumor lysis syndrome </li></ul></ul><ul><ul><ul><li>acute urate nephropathy </li></ul></ul></ul><ul><ul><li>ethylene glycol toxicity </li></ul></ul><ul><ul><ul><li>calcium oxylate deposition </li></ul></ul></ul><ul><li>Intratubular protein deposition </li></ul><ul><ul><li>multiple myeloma </li></ul></ul><ul><ul><ul><li>-Bence-Jones protein deposition </li></ul></ul></ul>
  60. 60. Differential Diagnosis of Acute Renal Failure <ul><li>Prerenal ARF </li></ul><ul><li>Postrenal ARF </li></ul><ul><li>Intrinsic ARF </li></ul><ul><ul><li>acute tubular necrosis </li></ul></ul><ul><ul><li>acute interstitial nephritis </li></ul></ul><ul><ul><li>acute glomerulonephritis </li></ul></ul><ul><ul><li>acute vascular syndromes </li></ul></ul><ul><ul><li>intratubular obstruction </li></ul></ul>
  61. 61. Acute Renal Failure: Diagnostic Evaluation <ul><li>Evaluate for prerenal causes </li></ul><ul><ul><li>clinical exam </li></ul></ul><ul><ul><ul><li>blood pressure </li></ul></ul></ul><ul><ul><ul><li>orthostasis </li></ul></ul></ul><ul><ul><li>central venous pressures and cardiac output </li></ul></ul><ul><ul><li>intake/output record </li></ul></ul><ul><ul><li>urine sediment </li></ul></ul><ul><ul><li>urine sodium </li></ul></ul><ul><ul><ul><li>U Na < 20 mmol/L </li></ul></ul></ul><ul><ul><li>therapeutic trial of volume replacement </li></ul></ul><ul><ul><li>skin turgor </li></ul></ul><ul><ul><li>mucosal membrane hydration </li></ul></ul><ul><ul><li>FE Na < 0.01 </li></ul></ul>
  62. 62. Acute Renal Failure: Diagnostic Evaluation <ul><li>Evaluate for postrenal causes </li></ul><ul><ul><li>bladder catheterization </li></ul></ul><ul><ul><li>renal ultrasound </li></ul></ul>
  63. 63. Acute Renal Failure: Diagnostic Evaluation <ul><li>Evaluation for intrinsic ARF </li></ul><ul><ul><li>clinical history </li></ul></ul><ul><ul><ul><li>medications </li></ul></ul></ul><ul><ul><ul><li>hypotension </li></ul></ul></ul><ul><ul><li>physical exam </li></ul></ul><ul><ul><li>urinalysis </li></ul></ul><ul><ul><ul><li>crystals </li></ul></ul></ul><ul><ul><ul><li>paraproteins </li></ul></ul></ul><ul><ul><li>radiocontrast agents </li></ul></ul><ul><ul><li>sepsis </li></ul></ul><ul><ul><li>cells </li></ul></ul><ul><ul><li>casts </li></ul></ul>
  64. 64. 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
  65. 65. Acute Renal Failure: Management <ul><li>Prerenal ARF </li></ul><ul><ul><li>volume repletion </li></ul></ul><ul><ul><li>inotropic support </li></ul></ul><ul><ul><li>discontinue diuretics </li></ul></ul><ul><li>Postrenal ARF </li></ul><ul><ul><li>bladder catheterization </li></ul></ul><ul><ul><li>percutaneous nephrostomy or ureteral stents </li></ul></ul><ul><ul><li>fluid management during post-obstructive diuresis </li></ul></ul>
  66. 66. Acute Renal Failure: Management <ul><li>Intrinsic ARF </li></ul><ul><ul><li>General supportive care </li></ul></ul><ul><ul><ul><li>fluid management </li></ul></ul></ul><ul><ul><ul><li>diuretics </li></ul></ul></ul><ul><ul><ul><li>bicarbonate supplementation </li></ul></ul></ul><ul><ul><ul><li>potassium </li></ul></ul></ul><ul><ul><ul><li>phosphate </li></ul></ul></ul><ul><ul><ul><li>drug dosing </li></ul></ul></ul><ul><ul><ul><li>nutrition </li></ul></ul></ul>
  67. 67. Acute Renal Failure: Management <ul><li>Indications for dialysis </li></ul><ul><ul><li>volume overload </li></ul></ul><ul><ul><li>metabolic acidosis </li></ul></ul><ul><ul><li>hyperkalemia </li></ul></ul><ul><ul><li>uremic syndrome </li></ul></ul><ul><ul><ul><li>pericarditis </li></ul></ul></ul><ul><ul><ul><li>encephalopathy </li></ul></ul></ul><ul><ul><li>azotemia </li></ul></ul>
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