Urinalysis: The forgotten fellow (Proceedings)
Day in and day out, clinical pathology is used to make diagnoses, assess response to treatment and to screen healthy animals for occult disease.
Day in and day out, clinical pathology is used to make diagnoses, assess response to treatment and to screen healthy animals for occult disease. What many call a "baseline database" includes a serum chemistry profile of some type, a complete blood count with blood smear evaluation and a complete urinalysis (dipstick and sediment examination). All too often, a urinalysis is not performed. Potential reasons include difficulty in obtaining samples, uncertainty in examining samples in house, sample handling issues during delay before processing and perceived lack of value. There are many reasons why a urinalysis should be performed as part of an initial work up on ALL cases, with serial examinations performed as needed.
The first, and arguably most important reason to perform a urinalysis CONCURRENTLY with a serum chemistry profile and complete blood count is in the evaluation of azotemia. Upon initial evaluation of a patient, it is absolutely imperative that a urinalysis be performed. Many commonly employed therapies will iatrogenically alter the kidney's ability to concentrate urine. Diet, glucocorticoids and diuretics are examples of things that can drastically alter the kidney's ability to concentrate urine; therefore, a urinalysis must be done prior to the initiation of therapy. Although of importance, the dipstick and sediment examination are not as crucial. To this end, even if only a few drops can be obtained using ultrasound guidance or catheterization, it is certainly to your advantage to obtain a urine specific gravity (USG). Your problem list and clinical decisions as to additional diagnostics, treatment, prognosis, etc. can be greatly affected. Likewise, if a case is ultimately referred, the receiving clinician will better be able to pick up the data and continue forward with USG information in hand.
Azotemia is defined as the excess of urea and other non-protein nitrogenous wastes in the blood. Although technically "serum" urea nitrogen, most people refer to it as "blood" urea nitrogen. That being said, urea is such a small molecule (60 Da), that it readily diffuses throughout the body, including into erythrocytes. Azotemia is generally sub-divided into three main categories: pre-renal, renal and post-renal. The bottom line is the magnitude of increase in BUN or creatinine cannot be used alone to subcategorize.
There are several causes of pre-renal azotemia. One cause is a decreased renal perfusion due to hypovolemia. Examples of this include: dehydration, shock and cardiac disease. Decreased flow rate allows greater resorption of BUN. Creatinine should also be similarly elevated. USG is generally elevated secondary to ADH secretion. A noted exception is hypoadrenocorticism. Another cause can be due to increased protein catabolism, such as with necrosis, starvation, prolonged exercise, infection, fever or corticosteroids. This hypercatabolic state leads to an increased generation of ammonia, which leads to an increase in production of urea. This leads to only a mild increase in BUN due to large renal reserve capacity. Creatinine should not be increased. High protein diets can also cause a pre-renal azotemia. An example of this mechanism is upper gastrointestinal bleeding and home-made diets. Creatinine should not be increased in these cases. Creatinine can be slightly elevated secondary to marked rhabdomyolysis; however, the elevation is mild. The BUN:Creatinine ratio may suggest certain etiologies (e.g. upper gastrointestinal bleeding); however, this index is insensitive and is fraught with overlap. With pre-renal azotemia, the fractional excretion of sodium (FE Na) should be very low. Pre-renal azotemia can, and often is, seen in combination with the other types of azotemia.
Renal azotemia implies that >75% of renal functioning mass is non-functional. GFR is significantly decreased; therefore, BUN / Creat are a poor indicator of renal disease, as they will not increase until a significant amount of disease is present. Once azotemia is present, BUN doubles each time the remaining functional mass decreases by half. At this stage of the disease, modest increases in BUN are highly significant. At this stage of disease, the kidney's ability to concentrate urine is usually compromised; however, cats occasionally are azotemic, yet retain some concentrating ability. In the face of physiologic states where water should be conserved, the USG for a dog should be greater than 1.030 and 1.035 for a cat. Primary glomerular disorders may develop azotemia without compromise of concentrating ability. Always be wary of non-renal diseases masquerading as CRF, such as hypoadrenocortisism.
Post renal azotemia is often diagnosed via physical examination, effusion analysis or using diagnostic imaging. Obstruction can cause release of vasoactive substances that cause vasoconstriction, reducing GFR, leading to pre-renal azotemia. The inability to excrete urine in obstructive cases leads to diffusion into the interstitium. Urinary obstruction also transiently increases intracapsular pressure, which decreases GFR, leading to a pre-renal component. Leakage of urine into the peritoneal space or other interstitial spaces equilibrates with plasma levels, leading to a rapid increase in BUN, which may limit its usefulness in diagnosis; therefore, fluid and serum creatinine levels should be compared. With post-renal azotemia, the USG is variable and depends on hydration status amongst other things.
A second, and potentially equally important reason to perform a urinalysis with the initial serum chemistry profile is to help evaluate hypoalbuminemia / hypoproteinemia. Kidneys normally allow small proteins (<68,000 Da) to pass the glomerulus, but they are resorbed in the PCT; therefore only a small amount of protein (<1+) should be present in the normal urine of dogs, with none to a trace in cats. BUN and creatinine will generally not be affected initially unless the total number of glomeruli is markedly decreased (if applicable). Blood and inflammation impact the amount of protein present and thus a clean cystocentesis sample with a benign sediment is required. Gross hematuria has been shown to significantly affect urine protein. Similar to nitrogenous wastes, drugs and treatments can affect the amount of protein lost in the urine; therefore, it's important to obtain an initial urinalysis as a baseline. With the urinalysis data in conjunction with the CBC and serum chemistry profile, the proteinuria may be able to classified as pre-renal, glomerular, tubular or hemorrhagic. If sub-categorization cannot be determined, additional test(s) can be identified to pursue. If needed, a urine protein to creatinine ratio (UPC) can be used to quantify renal loss of protein, which may ultimately lead to renal biopsy.
A third important clinical feature that can only be found on a urinalysis is cylinduria. The presence of casts typically indicates tubular injury. They consist of a matrix of Tamm-Horsfall protein, a mucoprotein produced by the tubular epithelial cells. They form in acidic urine and may dissolve in alkaline urine. Fresh urine must be evaluated, as they can break down at room temperature. Anything present in the tubular lumen at the time the cast is formed is embedded in the cast. Their presence does not correlate with severity of disease, and their absence does not exclude renal disease. The type of cast is classified based on the major component. They can also be pigmented (e.g. hemoglobin, myoglobin, etc.). They are best evaluated with low light and lowered sub-stage condenser. Tubular injury can be further be suggested by glucosuria without hyperglycemia (renal glucosuria). A GGT to creatinine ratio measured in the urine can be an additional test to evaluate tubular injury.
In addition to evaluation of azotemia and proteinuria, there are numerous other processes that are apparent only on the urinalysis or require a urinalysis to fully characterize. Due to the low renal threshold, bilirubinuria will precede hyperbilirubinemia in the feline, making it a sensitive method to detect early disease. Similarly, ketonuria occurs whenever there is ketonemia, which may only be signified by a change in anion gap and total carbon dioxide (TCO2). Normocytic, normochromic anemias can be due to a number of causes; however, credence can be given to a lack of erythropoietin (EPO) if a urinalysis is compatible with chronic renal disease.
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