• is a relatively abrupt reduction in the glomerular filtration rate (GFR) 
• as manifested by a rise in the plasma creatinine concentration (PCr) 
• and often by a fall in the daily urine volume. 

Disease that can cause Acute renal failure (ARF)

• Renal arteries: Stenosis
• Glomeruli: Glomerulonephritis
• Tubules: Acute tubular necrosis
• Interstitium: Drugs
• Obstruct the flow of urine from the kidney

75 % of all cases of ARF is most often the result of a 

• Fall in renal blood flow (Pre renal azotemia)
  • the kidney conserves sodium in true volume depletion 
  • This adaptation is appropriate because the effective arterial blood volume is reduced. 
• Damage to the renal tubules from a toxin or ischemia (Acute tubular necrosis)
  • the renal injury characteristic of ATN limits the normal capacity of the renal tubules to conserve fluid and electrolytes.
  • This limited ability to reabsorb sodium is caused by cell necrosis and possibly by translocation of the Na+-K+ ATPase from the basolateral (or blood) side of intact renal tubular cells to the luminal side

These differences in renal function are of primary importance in distinguishing between the major forms of ARF.

Differentiate prerenal azotemia from ATN 

• History and physical examination
  • The history and physical examination frequently reveal important diagnostic information
  • identification of potential causes of reduced renal perfusion or ATN
  • patient's extracellular fluid volume status
  • A renal ultrasound study should be performed in all individuals to detect possible urinary tract obstruction unless another cause of ARF is obvious.
•  Lab evaluation 
  • Ratio of Blood Urea Nitrogen to Creatinine
    • A fall in the GFR normally causes the BUN and creatinine concentrations to rise in equal proportions.
    • The enhanced salt and water avidity associated with prerenal states causes a disproportionate rise in the plasma ratio of BUN to creatinine. 
    • A ratio higher than 20:1 is suggestive of prerenal azotemia 
  • Urinalysis
    • The urinalysis is typically normal in prerenal azotemia, with the only common finding being the presence of hyaline casts. 
    • In ATN, by comparison, the urine characteristically contains many dark-brown granular casts with free renal tubular epithelial cells and epithelial cell casts 
  • Urinary Osmolality
    • The normal kidney can elaborate urine with a maximum concentration greater than 1,200 mOsm/kg in states of dehydration. 
    • A urinary osmolality (Uosm) greater than 500 mOsm/kg,, is highly suggestive of prerenal azotemia.
    • The capacity to perform this function is dependent on intact tubular function, particularly in the loop of Henle. 
    • In ATN there is damage in the loop of Henle, impairing the ability of the kidney to generate a high interstitial osmolality
    • Typically, the Uosm in ATN is approximately 300 to 350 mOsm/kg, a value that is similar to the plasma osmolality (Posm).
    • However, a Uosm of less than 500 mOsm/kg is often not diagnostically useful, because it can be seen in patients with ATN, prerenal disease, or underlying renal disease.
  • Urinary Sodium Concentration and Fractional Excretion of Sodium
    • Reduced renal perfusion is a potent stimulus for tubular sodium reabsorption. 
    • In prerenal azotemia, the UNa typically falls below 20 mEq/L
    • A higher UNa is characteristic of ATN.
    • The FENa is more specific than the UNa in distinguishing prerenal azotemia from ATN. 

Pre renal azotemia

A reduction in renal blood flow is the most common cause of ARF. 

• Usual causes 
  • True volume depletion
  • Advanced liver disease
  • CHF
•  CHF is associated with 
  • sodium retention 
  • a decline in the GFR 
• The decline in renal function is associated with the characteristic findings of prerenal disease: 
  • an elevated ratio of BUN to the Pcr
  • a normal urinalysis 
  • and a low UNa (< 20 mEq/L), unless diuretics have recently been given
• Pathogenesis
  • Excessive diuretic use
    • The administration of diuretics leads to fluid loss and a reduction in intravascular pressure. 
    •  The decline in left ventricular filling pressure often leads to a decrease in cardiac output.
  • Worsening cardiac function is a final cause of progressive prerenal disease in CHF. The fall in the GFR that might occur as renal blood flow is reduced in this setting is offset by two mechanisms: dilatation of the afferent (preglomerular) arteriole, which allows more of the systemic pressure to be transmitted to the glomerulus, and constriction of the efferent (postglomerular) arteriole, which further increases the filtration pressure across the glomerular capillaries.
  • Nonsteroidal anti-inflammatory drugs and ACE inhibitors: Contributing factor. In congestive heart failure (CHF) who have a low systemic blood pressure, the GFR may fall even though the ACE inhibitor increases cardiac output by lowering peripheral vascular resistance.

Acute Tubular Necrosis

• The characteristic tubular injury in ATN can occur in
  • renal ischemia 
  • exogenous or endogenous nephrotoxins
• Pathogenesis
  • There are two major histologic changes in ATN: 
    •  tubular necrosis with sloughing of the epithelial cells
    • occlusion of the tubular lumina by casts and by cellular debris 
  •  Changes are often patchy 
  •  Many nephrons drain into a single cortical collecting tubule, thus obstruction of a seemingly small number of collecting tubules can lead to marked renal dysfunction
  • In addition to tubular obstruction, two other factors appear to contribute to the development of renal
    failure in ATN: 
    • backleak of filtrate across the damaged tubular epithelia 
    • a primary reduction in glomerular filtration
• Post ischemic Acute Tubular Necrosis
  • severe ischemia 
  • major surgery
    •  preoperative fluid depletion
    • anesthesia
    • intraoperative fluid losses
    • hemolysis 
    • hypotension
• Certain surgical procedures seem to place patients at a much higher risk for ATN. 
  • Abdominal aortic aneurysm
    • total renal ischemia may occur when suprarenal aortic clamping is required
  • Surgery to correct obstructive jaundice
    • endotoxin absorption from the gut is important in this regard. 
  • Cardiac surgery also predisposes to ATN
    • underlying heart disease
    • hypotension
    • hemolysis during cardiopulmonary bypass
• Clinical presentation and course
  • It typically begins abruptly after a hypotensive episode, rhabdomyolysis, or the administration of radiocontrast media.
  • BUN and the PCr usually rise in daily increments of 10 to 25 mg/dl and 0.5 to 2.5 mg/dl, respectively. 
  • The rise in BUN, however, can reach 50 mg/dl/day or more in hypercatabolic patients (particularly those receiving parenteral amino acid solutions); marked hyperkalemia is also more common in this setting.
  • Although the GFR may fall to very low levels in patients with ATN, this change is not necessarily associated with a parallel reduction in urine output, which can range from oliguric levels (< 400 to 500 ml/day) to relatively normal values.
  • The renal failure phase in ischemic ATN generally lasts seven to 21 days, with most patients experiencing a return to their baseline level of renal function. 
  • Renal function usually returns to baseline within one to three days, if the duration of ischemia is short