Acute Renal Failure

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Acute Renal Failure

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

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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

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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

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Manifestations of ARF

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

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Differential Diagnosis of Azotemia

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

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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

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Classification of the Etiologies of Acute Renal
Failure
Acute Renal Failure
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Physiologic Response to Volume Depletion
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Prerenal Acute Renal Failure
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Pathogenesis of Prerenal Azotemia
Renal Vasoconstriction
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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

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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

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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

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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

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Fractional Excretion of Sodium
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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

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Treatment of Prerenal Acute Renal Failure

• Correction of volume deficits
• Discontinuation of antagonizing medications
• NSAIDs/COX-2 inhibitors
• Diuretics
• Optimization of cardiac function

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Postrenal Acute Renal Failure

• Urinary tract obstruction
• level of obstruction
• upper tract (ureters)
• lower tract (bladder outlet or urethra)
• degree of obstruction
• partial
• complete

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Postrenal Acute Renal Failure
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Postrenal Acute Renal Failure
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Postrenal Acute Renal Failure
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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

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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

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Postrenal Acute Renal FailureClinical
Presentation

• History
• Symptoms of bladder outlet obstruction
• urinary frequency
• urgency
• intermittency
• hesitancy
• nocturia
• incomplete voiding

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Postrenal Acute Renal FailureClinical
Presentation

• History
• Changes in urine volume
• anuria
• polyuria
• fluctuating urine volume
• Flank pain
• Hematuria
• History of pelvic malignancy

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Postrenal Acute Renal FailureClinical
Presentation

• Physical Examination
• Suprapubic mass
• Prostatic enlargement
• Pelvic masses
• Adenopathy

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Postrenal Acute Renal FailureClinical Evaluation

• Diagnostic studies
• BUN Creatinine ratio gt 201
• Unremarkable urine sediment
• Variable urine chemistries

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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

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Renal Ultrasound - Hydronephrosis
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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

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Intrinsic Acute Renal Failure

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

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Acute Tubular Necrosis
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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

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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
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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

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Phases of Ischemic ATN
Prerenal
Initiation
GFR
Extension
Recovery
Maintenance
Time
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Pathophysiology of ATN
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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

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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

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Acute Tubular Necrosis Clinical Presentation
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Acute Tubular NecrosisTreatment

• Supportive therapy
• No specific pharmacologic treatments
• Acute dialysis for
• volume overload
• metabolic acidosis
• hyperkalemia
• uremic syndrome
• pericarditis
• encephalopathy
• azotemia

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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

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Mortality in Acute Tubular Necrosis
Number of Failed Non-Respiratory Organ Systems
Chertow et al Arch Int Med 1995 1551505-1511
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Effect of Contrast Nephropathy on Mortality
Levy et al JAMA 1996 2751489-1494
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Acute Interstitial Nephritis

• Acute renal failure due to lymphocytic
  infiltration of the interstitium
• Classic triad of
• fever
• rash
• eosinophilia

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Acute Interstitial Nephritis
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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

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Acute Interstitial NephritisClinical
Presentation

• History
• preceding illness or drug exposure
• Physical examination
• fever
• rash
• Laboratory Findings
• eosinophilia

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Acute Interstitial NephritisClinical
Presentation

• Urine findings
• non-nephrotic protinuria
• hematuria
• pyuria
• WBC casts
• eosinophiluria

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Acute Interstitial NephritisClinical
Presentation
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Acute Interstitial NephritisClinical
Presentation
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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

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Acute Glomerulonephritis

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

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Acute Glomerulonephritis
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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

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Atheroembolic Disease
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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

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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

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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

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Acute Renal FailureDiagnostic Evaluation

• Evaluate for postrenal causes
• bladder catheterization
• renal ultrasound

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Acute Renal FailureDiagnostic Evaluation

• Evaluation for intrinsic ARF
• clinical history
• medications
• hypotension
• physical exam
• urinalysis
• crystals
• paraproteins

• radiocontrast agents
• sepsis
• cells
• casts

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Diagnostic Evaluation of ARF
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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

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Acute Renal Failure Management

• Intrinsic ARF
• General supportive care
• fluid management
• diuretics
• bicarbonate supplementation
• potassium
• phosphate
• drug dosing
• nutrition

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Acute Renal Failure Management

• Indications for dialysis
• volume overload
• metabolic acidosis
• hyperkalemia
• uremic syndrome
• pericarditis
• encephalopathy
• azotemia