In previous editions ofdvm360(Watch thedvm360.com/OsborneIn "The Full Story") we discuss various aspects of urine specific gravity values and their impact on patient health. Here we discuss the specific values of the urine and the location of the azotemia.
Note that some azotemic cats with primary renal failure retain a comparatively greater urine concentrating capacity than dogs. In dogs with progressive disease leading to primary renal failure, azotemia generally follows the loss of the ability to concentrate urine to a specific gravity of at least 1.030. In some cats with primary renal failure, azotemia may precede the loss of the ability to concentrate urine to levels of 1.040 to 1.045.
Prerenal anemia
Causes and pathogenesis.Diseases outside the urinary tract can lead to varying degrees of impairment of glomerular filtration due to reduced renal blood flow. Regardless of the cause, insufficient perfusion of normal glomeruli with blood can cause prerenal azotemia.
Prerenal azotemia is initially associated with structurally normal kidneys capable of quantitatively normal renal function provided that the compromised renal perfusion is corrected prior to the onset of ischemic damage to the nephron. Progression from prerenal azotemia to intrarenal (primary) kidney failure due to persistent ischemia prolongs and decreases the likelihood of full recovery.
Consider prerenal azotaemia when abnormal elevations in blood urea nitrogen (BUN) and creatinine concentrations are associated with sufficiently concentrated urine (1035 in dogs; 1040 in cats) in patients without specific evidence of systemic glomerular disease. Sufficiently concentrated urine associated with azotemia indicates that there are sufficient functional nephrons to prevent primary renal azotemia. Significantly elevated levels of BUN or creatinine due to primary renal failure in dogs may not be detected until approximately 70 to 75 percent of the nephron population is nonfunctional. The increased urine specific gravity associated with prerenal azotemia likely reflects a compensatory response by the body to combat low perfusion pressure and blood volume by secreting antidiuretic hormones (and possibly other substances) to conserve filtered water through the urine . Adequate volume replacement therapy to restore renal perfusion is usually followed by a dramatic fall in urea and creatinine concentrations to normal within about 1 to 3 days.
Another form of potentially reversible prerenal azotemia associated with primary renal disease may develop in patients with glomerulonephropathy and severe hypoalbuminemia. At the glomerular level, hypoalbuminemia increases the glomerular filtration rate due to decreased colloid osmotic pressure. However, decreased renal blood flow and glomerular filtration, which occur in conjunction with a significant reduction in vascular volume due to a decrease in colloid osmotic pressure, result in a proportionate degree of retention of substances normally eliminated by the kidneys (e.g. creatinine, urea). These two mechanisms have opposite effects on glomerular filtration. Therefore, carefully interpret an abnormal increase in urea or creatinine concentration (or a decrease in creatinine clearance) in hypoproteinemic nephrotic patients. Azotemia is not indisputable evidence of severe primary glomerular lesions, as a component of azotemia may be associated with a potentially reversible decrease in renal perfusion caused by hypoalbuminemia.
Diagnose.The diagnosis of prerenal azotemia is based on the following:
>Elevated serum BUN or creatinine concentrations
>Oliguria
>High urine specific gravity (1.035 in dogs; 1.040 in cats) or osmolality
>Identifying the root cause
>Rapid correction of azotemia after administration of appropriate therapy to restore renal perfusion.
Forecast.The prognosis of prerenal azotemia depends on the reversibility of the primary cause. The prognosis for kidney function is favorable if blood flow is restored quickly. However, a complete loss of renal perfusion for more than two to four hours can result in systemic ischemic kidney disease. With the exception of shock, this level of decreased renal perfusion is uncommon. Therefore, the onset of generalized renal disease would be expected to require a prolonged period of compromised renal perfusion.
Postrenal Anemia
pathogenesis.Diseases that prevent urine output can cause postrenal azotemia. The kidneys are initially structurally normal and able to function quantitatively normally provided the underlying cause is corrected. However, if the underlying cause persists, death occurs within days from fluid, electrolyte, acid-base, and hormonal imbalances and accumulation of metabolic waste products. If the flow of urine is only partially obstructed and the patient is able to survive longer, varying degrees of hydronephrosis can result.
Causes.Complete obstruction of urinary flow (ie, obstruction in the urethra, bladder, or both ureters) for more than 24 hours usually results in postrenal azotemia. Unilateral ureteral obstruction (an example of kidney disease) is not associated with azotemia unless generalized disease of the unobstructed kidney is also present. Azotemia, which results from disruption of the excretory pathway (usually the bladder), is primarily related to the absorption of urine from the abdominal cavity. Unless damaged by hypovolemic shock or trauma resulting from excretory tract dysfunction, the kidneys are structurally and functionally normal.
Diagnose.The diagnosis of postrenal azotemia is based on the integration of clinical findings. Lesions that cause obstruction to urine flow are commonly associated with:
>Elevated serum BUN and creatinine concentrations
>oliguria or anuria, dysuria and tenesmus
>Obstructive lesions detected by physical examination (eg, urethral plugs, bladder prolapse), x-rays, ultrasound, etc.
>Different values of specific gravity of urine
Disorder of the elimination tract is often associated with:
>Progressively increased serum BUN or creatinine concentrations
>Progressive depression, abdominal pain, ascites
>A history of trauma and associated physical examination findings
>Inability to palpate the urinary bladder
>Evidence of transudate or exudate modified by abdominocentesis
>Abnormalities detected by ultrasonography or cystography or urethrocystography with retrograde contrast (positive or negative).
Because of variability, urine specific gravity from patients with postrenal azotemia is not used to assess renal function to the same extent as in patients with primary and prerenal renal azotemia.
Prognosis associated with obstructive lesions.If the patient has complete obstruction of urinary flow for three to six days, it will result in death from uremia caused by abnormal fluid, acid-base, electrolyte, nutrient, and hormonal balance and accumulation of metabolic waste products. Death usually occurs before significant hydronephrosis develops. The prognosis is favorable if the obstructive lesion(s) are removed promptly. The long-term prognosis depends on the reversibility of the underlying cause.
Prognosis associated with rupture of the excretory tract.If a persistent tear in the excretory tract results in progressive azotemia, the patient is likely to die if the tear is not repaired. The prognosis for restoration of adequate renal function is favorable when the tear is repaired or healed. The long-term prognosis depends on the reversibility of the underlying cause.
primary intrarenal azaemia
pathogenesis.Intrarenal azotemic renal failure can be caused by many disease processes that destroy about three-fourths or more of the parenchyma of both kidneys. Depending on the biological behavior of the disease, primary renal failure associated with intrarenal azotemia can be reversible or irreversible and be acute or chronic. Irreversible azotemic chronic renal failure is usually slowly progressive.
Diagnose.In dogs, if a dehydrated patient has a reduced ability to concentrate urine, at least two-thirds of the nephron mass must be impaired. Complete loss of the ability to concentrate and dilute urine does not always occur suddenly, but often develops gradually. Therefore, a urine specific gravity between 1.007 and 1.029 in dogs or between 1.007 and 1.039 in cats associated with clinical dehydration or azotemia suggests intrarenal azotemia. Complete inability of the nephrons to concentrate or dilute urine (calledDetermine specific gravityÖIsostenurie) leads to a urine formation similar to that of the glomerular filtrate (approx. 1.008 to 1.012).
If a hydrated patient has elevated BUN and creatinine levels and a decreased ability to concentrate or dilute urine, it is likely that at least three-quarters of the functional capacity of the nephron mass is impaired.
More definitive studies (eg, ultrasonography, radiography, biopsy, exploratory surgery) are needed to determine the underlying cause of primary azotemic renal failure. When formulating a prognosis and therapy, remember that uremic signs are not directly caused by kidney damage but are related to differential fluid, acid-base, electrolyte, and nutrient imbalances; vitamin and endocrine disorders; and retention of waste products from protein catabolism that develop as a result of nephron dysfunction caused by an underlying disease (Table 1).
Tabla 1
Azotemia associated with glomerulotubular imbalance.In some patients with primary renal failure caused by generalized glomerular disease, abnormally elevated BUN or creatinine concentrations may be associated with variable urine concentrations. Be careful not to overinterpret the absolute value of urine specific gravity in these patients as it may be slightly elevated due to protein action. The addition of 40 mg protein/100 ml urine increases the urine specific gravity by about 0.001.
Renal injury should be characterized by glomerular damage severe enough to affect renal urea and creatinine clearance but not yet inducing sufficient ischemic atrophy and renal tubular cell or necrosis to prevent variable degrees of urine concentration. The glomerular filtrate that forms can therefore accumulate to such an extent that it is initially referred to as prerenal azotemia. However, this patient group can be distinguished from patients with prerenal azotemia by failure to look for one of the extrarenal causes of poor perfusion, persistent proteinuria, and persistent azotemia despite restoration of vascular volume and perfusion with proper therapy.
Azotämie-Combination
pathogenesis.Severely diseased kidneys have a reduced ability to compensate for the stress caused by disease states, poor diet, and changes in the environment. In patients with previously compensated primary renal disease, uraemic crises are often triggered or complicated by a variety of concomitant extrarenal factors.
Extrarenal mechanisms that may be associated with uremic crises include:
>Factors that accelerate the body's breakdown of protein increase the amount of metabolic by-products in the body because the kidneys cannot eliminate them. Protein by-products contribute significantly to the development of uremic signs in patients with renal failure.
>Stress conditions (fever, infection, change of environment) are associated with the release of glucocorticoids from the adrenal glands.
>Glucocorticoids stimulate the conversion of protein into carbohydrates (gluconeogenesis) and thus increase the amount of protein waste products in the body.
>Abnormalities that decrease renal blood flow (eg, decreased water intake, vomiting, diarrhea) cause prerenal uraemia.
>Nephrotoxic drugs can induce an acute uremic crisis in patients with chronic renal failure by damaging the nephrons.
Diagnose.Combinations of causes of azotemia should be based on:
>History of compensated primary renal failure
>Detection of primary extrarenal disease processes as well as generalized kidney diseases
>Screening for clinical dehydration: Dehydration associated with azotemia and decreased urine concentration is reliable evidence that part of the azotemia is of prerenal origin.
>How the patient responds to treatment: Uremic crises triggered by reversible extrarenal diseases can respond rapidly to symptomatic and supportive treatment (rapid and significant reduction in the extent of azotemia). Uremic crises, caused by progressive irreversible destruction of the nephrons, usually respond more slowly (a small reduction in the extent of azotemia).
Forecast.Wait until the extent of azotemia is reassessed after correction of the prerenal or postrenal components of azotemia before establishing a prognosis.
dr Carl A. Osborne is Director of the Minnesota Urolith Center and Professor in the College of Veterinary Medicine at the University of Minnesota. dr Eugene Nwaokorie is a PhD student at the University of Minnesota.