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Acute Renal Failure

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Title: Acute Renal Failure


1
Acute Renal Failure
  • Paul M. Palevsky, M.D.
  • Professor of Medicine
  • Chief, Renal Section
  • VA Pittsburgh Healthcare System

2
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

3
Relationship Between GFR and Serum Creatinine in
ARF
120
80
GFR (mL/min)
40
0
6
Serum Creatinine (mg/dL)
4
2
0
0
7
14
21
28
Days
4
Acute Renal Failure
  • Definitions
  • Azotemia - the accumulation of nitrogenous wastes
  • Uremia - symptomatic renal failure
  • Oliguria - urine output lt 400-500 mL/24 hours
  • Anuria - urine output lt 100 mL/24 hours

5
Manifestations of ARF
  • Azotemia progressing to uremia
  • Hyperkalemia
  • Metabolic acidosis
  • Volume overload
  • Hyperphosphatemia
  • Accumulation and toxicity of medications excreted
    by the kidney

6
Differential Diagnosis of Azotemia
  • Etiologies of acute elevations of BUN
  • Acute renal failure
  • Protein loading
  • GI bleeding
  • Catabolic steroids
  • Tetracycline antibiotics

7
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

8
Classification of the Etiologies of Acute Renal
Failure
Acute Renal Failure
9
Physiologic Response to Volume Depletion
10
Prerenal Acute Renal Failure
11
Pathogenesis of Prerenal Azotemia
Renal Vasoconstriction
12
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

13
Prerenal Acute Renal FailureClinical
Presentation
  • History
  • volume loss (e.g., diarrhea, acute blood loss)
  • heart disease
  • liver disease
  • evidence of infection
  • diuretic use
  • thirst
  • orthostatic symptoms

14
Prerenal Acute Renal FailureClinical
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

15
Prerenal Acute Renal Failure Clinical
Presentation
  • BUNCreatinine ratio
  • gt 201
  • Urine indices
  • Oliguria
  • usually lt 500 mL/24 hours but may be
    non-oliguric
  • Elevated urine concentration
  • UOsm gt 700 mmol/L
  • specific gravity gt 1.020
  • Evidence of high renal sodium avidity
  • UNa lt 20 mmol/L
  • FENa lt 0.01
  • Inactive urine sediment

16
Fractional Excretion of Sodium
17
Fractional Excretion of Sodium
  • Etiologies of a fractional excretion of sodium lt
    0.01
  • normal renal function
  • prerenal azotemia
  • hepatorenal syndrome
  • early obstructive uropathy
  • contrast nephropathy
  • rhabdomyolysis
  • acute glomerulonephritis

18
Treatment of Prerenal Acute Renal Failure
  • Correction of volume deficits
  • Discontinuation of antagonizing medications
  • NSAIDs/COX-2 inhibitors
  • Diuretics
  • Optimization of cardiac function

19
Postrenal Acute Renal Failure
  • Urinary tract obstruction
  • level of obstruction
  • upper tract (ureters)
  • lower tract (bladder outlet or urethra)
  • degree of obstruction
  • partial
  • complete

20
Postrenal Acute Renal Failure
21
Postrenal Acute Renal Failure
22
Postrenal Acute Renal Failure
23
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

24
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

25
Postrenal Acute Renal FailureClinical
Presentation
  • History
  • Symptoms of bladder outlet obstruction
  • urinary frequency
  • urgency
  • intermittency
  • hesitancy
  • nocturia
  • incomplete voiding

26
Postrenal Acute Renal FailureClinical
Presentation
  • History
  • Changes in urine volume
  • anuria
  • polyuria
  • fluctuating urine volume
  • Flank pain
  • Hematuria
  • History of pelvic malignancy

27
Postrenal Acute Renal FailureClinical
Presentation
  • Physical Examination
  • Suprapubic mass
  • Prostatic enlargement
  • Pelvic masses
  • Adenopathy

28
Postrenal Acute Renal FailureClinical Evaluation
  • Diagnostic studies
  • BUN Creatinine ratio gt 201
  • Unremarkable urine sediment
  • Variable urine chemistries

29
Postrenal Acute Renal FailureClinical Evaluation
  • Diagnostic studies
  • Post-void residual bladder volume
  • gt 100 mL consistent with voiding dysfunction
  • Radiologic studies
  • Ultrasound
  • CT scan
  • Nuclear medicine
  • Retrograde pyelography
  • Antegrade nephrostograms

30
Renal Ultrasound - Hydronephrosis
31
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

32
Intrinsic Acute Renal Failure
  • Acute tubular necrosis (ATN)
  • Acute interstitial nephritis (AIN)
  • Acute glomerulonephritis (AGN)
  • Acute vascular syndromes
  • Intratubular obstruction

33
Acute Tubular Necrosis
34
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

35
Pathophysiology of ATNTubular Epithelial Cell
Injury and Repair
Ischemia/ Reperfusion
Necrosis
Apoptosis
Loss of polarity
Normal Epithelium
Cell death
Differentiation Reestablishment of polarity
Sloughing of viable and dead cells with luminal
obstruction
Proliferation
Adhesion molecules
Na/K-ATPase
Migration , Dedifferentiation of Viable Cells
36
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

37
Phases of Ischemic ATN
Prerenal
Initiation
GFR
Extension
Recovery
Maintenance
Time
38
Pathophysiology of ATN
39
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
  • BUNCreatinine ratio lt 101
  • Evidence of toxin exposure

40
Acute Tubular Necrosis Clinical Presentation
  • Urine indices
  • Urine volume
  • may be oliguric or non-oliguric
  • Isosthenuric urine concentration
  • UOsm ? 300 mmol/L
  • specific gravity ? 1.010
  • Evidence of renal sodium wasting
  • UNa gt 40 mmol/L
  • FENa gt 0.02
  • Urine sediment
  • tubular epithelial cells
  • granular casts

41
Acute Tubular Necrosis Clinical Presentation
42
Acute Tubular NecrosisTreatment
  • Supportive therapy
  • No specific pharmacologic treatments
  • Acute dialysis for
  • volume overload
  • metabolic acidosis
  • hyperkalemia
  • uremic syndrome
  • pericarditis
  • encephalopathy
  • azotemia

43
Prognosis ofAcute 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

44
Mortality in Acute Tubular Necrosis
Number of Failed Non-Respiratory Organ Systems
Chertow et al Arch Int Med 1995 1551505-1511
45
Effect of Contrast Nephropathy on Mortality
Levy et al JAMA 1996 2751489-1494
46
Acute Interstitial Nephritis
  • Acute renal failure due to lymphocytic
    infiltration of the interstitium
  • Classic triad of
  • fever
  • rash
  • eosinophilia

47
Acute Interstitial Nephritis
48
Acute Interstitial Nephritis
  • Drug-induced
  • penicillins
  • cephalosporins
  • sulfonamides
  • rifampin
  • phenytoin
  • furosemide
  • NSAIDs
  • Malignancy
  • Idiopathic
  • Infection-related
  • bacterial
  • viral
  • rickettsial
  • tuberculosis
  • Systemic diseases
  • SLE
  • sarcoidosis
  • Sjögrens syndrome
  • tubulointerstitial nephritis and uveitis

49
Acute Interstitial NephritisClinical
Presentation
  • History
  • preceding illness or drug exposure
  • Physical examination
  • fever
  • rash
  • Laboratory Findings
  • eosinophilia

50
Acute Interstitial NephritisClinical
Presentation
  • Urine findings
  • non-nephrotic protinuria
  • hematuria
  • pyuria
  • WBC casts
  • eosinophiluria

51
Acute Interstitial NephritisClinical
Presentation
52
Acute Interstitial NephritisClinical
Presentation
53
Acute Interstitial NephritisTreatment
  • Discontinue offending drug
  • Treat underlying infection
  • Treat systemic illness
  • Glucocorticoid therapy may be used in patients
    who fail to respond to more conservative therapy

54
Acute Glomerulonephritis
  • Nephritic presentation
  • proteinuria
  • may be in nephrotic range (gt 3 g/day)
  • hematuria
  • RBC casts
  • Diagnosis usually requires renal biopsy

55
Acute Glomerulonephritis
56
Acute Glomerulonephritis
  • Etiologies
  • poststreptococcal glomerulonephritis
  • postinfectious glomerulonephritis
  • endocarditis-associated glomerulonephritis
  • systemic vasculitis
  • thrombotic microangiopathy
  • hemolytic-uremic syndrome
  • thrombotic thrombocytopenic purpura
  • rapidly progressive glomerulonephritis

57
Acute Vascular Syndromes
  • Renal artery thromboembolism
  • Renal artery dissection
  • Renal vein thrombosis
  • Atheroembolic disease

58
Atheroembolic Disease
59
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

60
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

61
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
  • UNa lt 20 mmol/L
  • therapeutic trial of volume replacement
  • skin turgor
  • mucosal membrane hydration
  • FENa lt 0.01

62
Acute Renal FailureDiagnostic Evaluation
  • Evaluate for postrenal causes
  • bladder catheterization
  • renal ultrasound

63
Acute Renal FailureDiagnostic Evaluation
  • Evaluation for intrinsic ARF
  • clinical history
  • medications
  • hypotension
  • physical exam
  • urinalysis
  • crystals
  • paraproteins
  • radiocontrast agents
  • sepsis
  • cells
  • casts

64
Diagnostic Evaluation of ARF
65
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

66
Acute Renal Failure Management
  • Intrinsic ARF
  • General supportive care
  • fluid management
  • diuretics
  • bicarbonate supplementation
  • potassium
  • phosphate
  • drug dosing
  • nutrition

67
Acute Renal Failure Management
  • Indications for dialysis
  • volume overload
  • metabolic acidosis
  • hyperkalemia
  • uremic syndrome
  • pericarditis
  • encephalopathy
  • azotemia
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