Urea nitrogen and Creatinine

• decreased renal perfusion due to hypovolemia or cardiac dysfunction (prerenal causes)
• loss of functional nephrons (renal causes)
• combination of the two above causes

Azotemia

Azotemia is defined as an increase in urea nitrogen (UN) and creatinine and can result form a variety of disorders including, but not limited to, renal failure. Uremia is the term for the clinical syndrome of renal failure with azotemia and multisystemic problems such as polyuria, polydipsia, mild non-regenerative anemia (in chronic renal failure), vomiting, weight loss, depression, and other sequelae of inadequate renal function.

Azotemia can be due to prerenal, renal or post-renal causes. Differentiation of the causes of azotemia requires urinalysis (especially assessment of urine specific gravity), evaluation of clinical signs and results of other diagnostic tests (e.g. radiographic evidence of urinary tract obstruction). Remember that the kidney is essential to acid-base and electrolyte homeostasis. Severe pre-renal azotemia, renal azotemia and severe post-renal azotemia may result in retention of organic acids normally excreted by the kidney (i.e. a high anion gap metabolic acidosis), hypermagnesemia and hyperphosphatemia.

• Prerenal azotemia
  Prerenal azotemia is due to a decrease in GFR from circulatory disturbances causing decreased renal perfusion, such as hypovolemia (shock, hemorrhage, Addison's disease, vomiting), cardiac disease or renal vasoconstriction. Prerenal azotemia can usually be distinguished from renal azotemia by clinical signs (evidence of dehydration or hypovolemia), urinalysis (urine should be concentrated, i.e. > 1.030 in the dog, > 1.035 in the cat, > 1.025 in large animals; and there should be no other evidence of renal tubule dysfunction such as proteinuria, cylindriuria) and response to therapy. Urine specific gravity may be decreased (despite a prerenal azotemia) if there are other factors reducing the concentrating ability of the kidney (see urine specific gravity). Therefore, often a response to therapy (fluid administration) is required to differentiate between a primary renal and prerenal azotemia (the azotemia should correct with appropriate fluid therapy within 24-48 hours in a pre-renal azotemia) . Note that many causes of a prerenal azotemia will result in renal hypoxia and ischemia. If this is severe or chronic enough, a primary renal azotemia may result, and may co-exist with a renal azotemia.
  As UN levels in blood are dependent on flow rate through the renal tubules (decreased flow rate in prerenal azotemia enhances renal absorption of UN, and increases UN levels in blood), UN may increase without any increase in creatinine in early pre-renal azotemias.
  
  
• Renal azotemia
  Renal azotemia results from a decreased GFR when more than 3/4 of the nephrons are non-functional. Renal azotemia may be due to primary intrinsic renal disease (glomerulonephritis, ethylene glycol toxicity) or may be secondary to renal ischemia from prerenal causes or from kidney damage from urinary tract obstruction (post-renal azotemia). Loss of 3/4 of kidney function usually follows concentrating defects (requires loss of 2/3 of the kidney), therefore isosthenuric urine (usg 1.008-1.012) is common in renal azotemia. In addition, there may be other evidence of renal tubular dysfunction in the urinalysis, such as proteinuria, granular or cellular casts, and glucosuria without hyperglycemia (these features are not always present in urine from animals with a renal azotemia). Azotemia with a urine specific gravity less than those values stated above is presumptive evidence of renal azotemia or renal failure UNLESS there is also evidence of other diseases or conditions affecting urine concentrating ability independently of renal failure. The greatest difficulty in differentiating renal from prerenal azotemia is encountered in those cases with a urine specific gravity greater than isosthenuric (1.012), but < 1.030 in the dog, < 1.035 in the cat and < 1.025 in large animals.
  Note that in cats, primary glomerular disease may occur without loss of renal concentrating ability (so the cat may have renal azotemia with concentrated urine).
  In horses and cattle, increases in UN are modest in renal azotemia due to excretion of UN into the gastrointestinal system (the urea is broken down into amino acids in the cecum and rumen, respectively). Therefore, creatinine is a more reliable indicator of GFR in these species.
  The following electrolyte abnormalities are observed in different species with renal failure:
  As mentioned above, a high anion gap metabolic acidosis is common in all species with renal failure. Hypermagnesemia and hyperkalemia are features of oliguric or anuric renal failure in all species.

• Bovine: Decreased sodium chloride are seen, with decreases in chloride being most consistent. This is associated with a concurrent metabolic alkalosis. Hypokalemia may be seen in polyuric renal failure, and hyperkalemia is seen in oliguric renal failure. Hypocalcemia (total calcium) is common as is increased fibrinogen.
• Equine: Often see a decrease in sodium chloride (especially chloride). In acute renal failure, total calcium is often low and phosphate is high (especially in young horses), whilst in chronic renal failure, hypercalcemia (total calcium) and hypophosphatemia occur (not in all cases). Hyperkalemia is a feature (with low sodium and chloride) of uroabdomen.
• Small animals: Hyperkalemia is usually only seen in anuric or oliguric renal failure. Total calcium is often normal (may be increased or decreased, especially in the dog), hypokalemia is common in cats in polyuric renal failure and hyperfibrinogenemia is often seen in cats with acute or chronic renal failure.
  
  
• Post-renal azotemia
  Post-renal azotemia results from obstruction (urolithiasis) or rupture (uroabdomen) of urinary outflow tracts. This is best diagnosed by clinical signs (e.g. frequent attempts to urinate without success or presence of peritoneal fluid due to uroabdomen) and ancillary diagnostic tests (e.g. inability to pass a urinary catheter) as urine specific gravity results are quite variable. Animals with post-renal azotemia are markedly hyperkalemic and hypermagnesemic. Uroperitoneum can be confirmed by comparing the concentration of creatinine in the fluid to that in serum or plasma; leakage of urine is indicated by a higher creatinine in fluid than in serum. Post-renal azotemia can result in primary renal azotemia (failure) due to tubule dysfunction from impaired renal flow.

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