Causes and pathogenesis: Non-urinary factors (consumption of high-protein diets, gastrointestinal hemorrhage) may result in mild increases in the
rate of production of urea (SUN = <60mg/dl; SC = normal). In this instance, both renal function and renal structure are normal.
Consult reference texts for further details. Non-urinary diseases may also reduce glomerular filtration as a result of reduction
or renal blood flow. Inadequate perfusion of normal glomeruli with blood, regardless of cause (dehydration, cardiac disease,
shock, hypoadrenocorticism, decreased plasma colloidal osmotic pressure) may cause prerenal azotemia (Table 1, case No. 2
and 4). Prerenal azotemia is initially associated with structurally normal kidneys capable of quantitatively normal renal
function, provided compromised renal perfusion is corrected prior to the onset of ischemic nephron damage. However, if poor
perfusion of the kidneys persists, prerenal azotemia may progress to intrarenal (primary) renal failure.
Diagnosis (Table 3) — A diagnosis of prerenal azotemia should be considered if abnormal elevation in the serum concentration of urea
nitrogen and creatinine is associated with adequately concentrated urine (specific gravity >1.030 in dogs; specific gravity
>1.035 in cats). Detection of adequately concentrated urine in association with azotemia indicates that a sufficient quantity
of functional nephrons (>1/3 in dogs) are present to prevent primary renal azotemia.
Significant elevations in the serum or plasma concentration of urea nitrogen or creatinine due to primary renal failure usually
is not recognized in dogs or cats until approximately 70 to 75 percent of the nephron population is nonfunctional. Elevation
in urine specific gravity associated with prerenal azotemia reflects a compensatory response by the body to combat low perfusion
pressure and blood volume by secreting antidiuretic hormone (and other substances) to conserve water filtered through glomeruli.
Table 3: Localization of different forms of azotemia
Following restoration of renal perfusion by appropriate volume replacement therapy, restoration of normal concentrations of
serum urea and creatinine typically occur in approximately one to three days.
Prognosis: The prognosis of prerenal azotemia is dependent on reversibility of primary cause. The prognosis is favorable for renal function
if perfusion is rapidly restored. However, complete loss of renal perfusion in excess of two to four hours may result in generalized
ischemic renal disease. With the exception of shock, this degree of reduced renal perfusion is uncommon. Thus the onset of
generalized renal disease would be expected to require a longer period of altered renal perfusion.
Causes and pathogenesis: Diseases that impair or prevent excretion or urine through the urinary tract may cause postrenal azotemia. In patients with
postrenal azotemia, the kidneys are structurally normal initially, and capable of quantitatively normal function provided
the underlying cause is corrected. However, if the underlying cause is allowed to persist, death from alterations in water,
electrolyte and acid-base and endocrine balance, in addition to accumulation of metabolic waste products, will occur within
a few days. If partial obstruction to urine outflow allows the patient to survive for a longer time, varying degrees of hydronephrosis
may subsequently occur.
Complete obstruction of urine outflow (i.e. obstruction in urethra, bladder or both ureters) that persists for more than 24
hours usually results in postrenal azotemia. Unilateral ureteral occlusion (an example of renal disease) is not associated
with azotemia unless generalized disease of the non-obstructed kidney is also present. Azotemia that occurs as a sequela to
rupture of the excretory pathway (most commonly the bladder) is primarily related to absorption of urine from the peritoneal
cavity. Unless damaged as a result of hypovolemic shock or trauma secondary to the underlying cause of rupture of the excretory
pathway, the kidneys are structurally and functionally normal.
Diagnosis: Because of variability, the urine specific gravity of patients with post-renal azotemia is not relied on to the same degree
for assessment of renal function as it is in patients with primary renal and prerenal azotemia. A diagnosis of post-renal
azotemia is based on the integration of clinical findings. Lesions causing urine outflow obstruction are commonly associated
1) elevation in serum urea nitrogen and creatinine concentration,
2) oliguria or anuria, dysuria and tenesmus,
3) detection of obstructive lesion(s) by physical examination (urethral plug, herniated bladder), radiography, ultrasonography,
4) variable urine specific gravity values (Table 1, Case 1). Rupture of the excretory pathway is commonly associated with:
- progressive elevation in serum urea nitrogen or creatinine concentration,
- progressive depression, painful abdomen, ascites;
- a history of trauma and associated physical examination findings,
- inability to palpate the urinary bladder,
- detection of a modified transudate or exudate by abdominocentesis;
- abnormalities detected by ultrasonography, or retrograde contrast (positive or negative) cystography or urethrocystography.
Prognosis of obstructive lesions: If the patient has total obstruction to urine outflow for a period of three to six days,
then death from uremia will occur. Death usually occurs before significant hydronephrosis has time to develop. Alteration
of fluid, acid-base, electrolyte, nutrient and endocrine balance, and accumulation of metabolic waste products cause death.
The prognosis is favorable for renal function if adequate urine outflow is rapidly restored. The long-term prognosis is dependent
on the reversibility of the underlying cause.
Prognosis of rupture of the excretory pathway: If a persistent rent in the excretory pathway is of sufficient magnitude to
result in progressive azotemia, then it is likely that the patient will die if it is not repaired. The prognosis for renal
function is favorable if the rent is repaired or heals. The long-term prognosis is dependent on the reversibility of the underlying
Primary intrarenal azotemia
Causes and pathogenesis: Intrarenal azotemic renal failure may be caused by a large number of disease processes (glomerular,
tubular, interstitial and/or vascular) which have in common damage of approximately three-fourths or more of the parenchyma
of both kidneys.
Diagnosis: In dogs, functional impairment of at least two-thirds of the nephrons is indicated if a dehydrated patient (that has not received
fluid, diuretic or glucocorticoid therapy) has impaired ability to concentrate urine. Total loss of ability to concentrate
and dilute urine does not always occur as a sudden event, but often develops gradually. For this reason, a urine specific
gravity between approximately 1.007 to 1.029 for dogs, or 1.007 to 1.034 for cats, associated with clinical dehydration or
azotemia is indicative of intrarenal azotemia (Table 1, Case 5 and 8, Table 3,). Total inability of the nephrons to concentrate
or dilute urine (so-called fixation of specific gravity or isosthenuria) results in the formation of urine that is similar
to that of glomerular filtrate (approximately 1.008 to 1.012).
If a hydrated patient has an elevation in the serum concentration of urea nitrogen and creatinine, and impaired ability to
concentrate or dilute urine, it is likely that impairment of at least three-fourths of the functional capacity of the nephron
mass has occurred. (Table 1, Case 3 and 6, p. 18S). Additional studies (ultrasonography, radiography, biopsy, exploratory
surgery) are required to establish the underlying cause of primary azotemic renal failure.
Prognosis: Depending on the biological behavior of the disease in question, primary renal failure associated with intrarenal azotemia
may be reversible or irreversible, acute or chronic, oliguric or polyuric. Chronic irreversible azotemic renal failure is
usually slowly progressive. When formulating a prognosis and therapy, recall that renal lesions do not directly cause uremic
signs. They are related to varying degrees of fluid, acid-base, electrolyte and nutrient imbalances, vitamin and endocrine
alterations, and retention of waste products of protein catabolism which develop as a result of nephron dysfunction caused
by an underlying disease.
Caveat: In dogs with progressive disease resulting in primary renal failure, intra-renal azotemia usually occurs after loss of the
ability to concentrate urine to at least a SG of 1.030. Likewise, most cats with naturally occurring primary renal diseases
associated with moderate to severe intrarenal azotemia (serum creatinine >3.5 mg/dl) cannot concentrate urine to specific
gravity values >1.035. However, we have encountered some cats with naturally occurring primary renal failure and mild azotemia
(serum creatinine < 3.5 mg/dl) that could concentrate urine to values substantially in excess of 1.040. Therefore, in cats
mild azotemia (serum creatinine = approximately 1.6 to 3.5 mg/dl) associated with urine specific gravity values >1.035 to
1.040 does not conclusively rule out intrarenal azotemia. Further studies of cats are needed to determine the urine SG value
that best indicates an adequate population of functional nephrons to prevent signs associated with primary renal failure.
Azotemia associated with glomerulotubular imbalance
Causes and pathogenesis: In some patients with primary renal failure caused by generalized glomerular disease, azotemia may be detected prior to marked
impairment in urine concentrating capacity (Table 3 ). The renal lesion in such patients must be characterized by glomerular
damage which is sufficiently severe to impair renal clearance of urea and creatinine, but which has not yet induced a sufficient
degree of ischemic atrophy and necrosis of renal tubular cells to prevent varying degrees of urine concentration.
Diagnosis: This group of patients may be differentiated from patients with pre-renal azotemia by failure of a search for one of the extrarenal
causes of poor perfusion, by persistent proteinuria and by persistent azotemia despite restoration of vascular volume and
perfusion with appropriate therapy (Table 1, Case 6; Table 3).
Caveat: Caution should be used when interpreting urine specific gravity values in patients with substantial proteinuria since specific
gravity may be slightly elevated by the effect of protein. Addition of 40 mg of protein per 100 ml of urine will increase
the urine specific gravity by approximately 0.001.
Combinations of primary intrerenal azotemia, prerenal azotemia and/or postrenal azotemia.
Pathogenesis: Many symptomatic azotemic patients with primary renal failure are clinically dehydrated. Dehydration associated with azotemia
and impaired urine concentration is evidence that a combination of intrarenal azotemia and prerenal azotemia are present.
Likewise, in recent years, we have encountered increasing numbers of cats with primary chronic azotemic renal failure that
have developed uremic crises as a result of postrenal azotemia caused by obstruction of one or both ureters with calcium oxalate
Diagnosis: Combinations of causes of azotemia should be considered on the basis of:
- a previous history of compensated primary renal failure,
- detection of primary extrarenal disease processes in addition to generalized renal disease,
- detection of clinical dehydration,
the patient's response to therapy (Table 1, Case 5 and 8 ). Patients with uremic crises precipitated by reversible extra-renal
factors (pancreatitis, dietary indiscretion) may rapidly respond to supportive and symptomatic therapy, as evidenced by a
rapid and significant reduction in the magnitude of azotemia. The therapeutic response of patients with uremic crises caused
by progressive irreversible destruction of nephrons is usually slower, as evidenced by only a marginal reduction in the magnitude
Prognosis: The influence of the severity of azotemia on the prognosis should be withheld until the magnitude of azotemia is reassessed
after correction of the prerenal or post-renal components.