RENAL DISEASE: DIAGNOSIS USING THE MINIMUM DATA-BASE Anne Barger, DVM, MS, DACVP University of Illinois, Urbana, IL

Renal disease is defined as the presence of morphologic renal lesions of any size or severity or any biochemical abnormalities indicative of abnormal renal function. Renal failure, on the other hand, is a combination of clinical signs and biochemical abnormalities indicative of decreased renal function. The kidney has a diverse list of functions. Its main function is the excretion of nitrogenous wastes. However, the kidneys also play a role in acid-base balance, regulation of body water, degradation of certain compounds and erythropoietin production/secretion.

Evaluation of renal function is a multifactorial process. Evaluation of the chemistry profile, urinalysis and CBC all contribute; however, the clinical presentation of the patient as well as a thorough physical examination are vital components. We use the chemistry profile to determine if the patient is azotemic. Azotemia, by definition, is an excess of urea or creatinine in the blood. With the assistance of the urinalysis and physical examination, we attempt to classify the azotemia as pre-renal, renal or post-renal.

Urea is a nitrogenous waste product used in part to evaluate renal function. Urea is formed in the liver. Protein is absorbed by the small intestine as amino acids. The amino acids are deaminated by the liver and the amine groups are incorporated into urea so they can be safely excreted by the kidney. Urea is excreted primarily by the kidney but to a lesser extent can also be excreted in the saliva and in horses, via the GI tract. This analyte is primarily measured as part of a chemistry panel; however, urea can be measured individually with a drop of blood on a reagent strip. This method is not ideal because it give a range rather than a number. Elevations in urea can occur with pre-renal, renal or post-renal azotemia. The most common cause of pre-renal azotemia is dehydration. As the glomerular filtration rate decreases, so does excretion of urea. Pre-renal elevations in urea can also occur with excessive protein metabolism either from increased protein digestion or increased protein catabolism secondary to fever. Renal elevations in urea occur when 75% of the nephrons are non-functional, making this a poorly sensitive indication of renal disease. Post-renal elevations of urea occur with obstruction of urine flow or uroperitoneum. Urea will return to normal quickly after the obstruction or leakage is repaired. Mechanisms of decreased urea include decreased production from hepatic insufficiency or low protein diet and increased excretion from excessive diuresis either from fluid therapy or PU/PD from non-renal diseases.

Creatinine is a non-protein nitrogen that is excreted almost exclusively by the kidney. Creatinine is a waste product of normal muscle metabolism and as such is produced and excreted at a fairly steady rate. Measurement of creatinine is an enzymatic or colorimetric test that can be performed on most chemistry analyzers. Elevations in creatinine are similar to that of urea, pre-renal from dehydration, renal associated with renal failure and post-renal from urinary obstruction or uroperitoneum. Diet or catabolic state only minimally impacts creatinine levels which distinguishes it from urea, although patients with severe muscle wasting may exhibit a decrease in creatinine.

Interpretation of azotemia must be done in conjunction with physical exam findings and urine specific gravity. If a patient is greater than 3% dehydrated, ADH is released and the urine is appropriately concentrated. Isosthenuria with azotemia is highly suggestive of renal failure although there are non-renal diseases such as hypoadrenocorticism which can impact the concentrating ability of the kidney.

There are many other abnormalities in the chemistry profile, CBC and urinalysis that can accompany renal disease. Hyperphosphatemia occurs as a direct result of decreased GFR and can be seen with pre-renal, renal or post-renal azotemia. Various electrolyte abnormalities can occur in patients with renal disease. Hyperkalemia can occur with oliguric or anuric renal failure. In patients with polyuric chronic renal failure, however, hypokalemia is much more common. Metabolic acidosis can occur by more than one mechanism. Titrational metabolic acidosis (decreased HCO3 with an elevated anion gap) occurs when the patient is producing increased uremic acids. Secretional metabolic acidosis occurs in renal tubular acidosis when the patient is excreting excessive bicarbonate via the renal tubules. Hypoalbuminemia associated with renal disease indicates significant glomerular or tubular disease and is generally accompanied by measureable proteinuria. Hyperalbuminemia indicates the patient is dehydrated.

Evaluation of the urinalysis can be very beneficial for multiple reasons. As mentioned above, determination of the urine concentration ability is vital for the appropriate interpretation of the chemistry data. Urine specific gravity (USG) is a simple in-house test that is vital in the diagnosis of renal failure. If the patient is dehydrated, the urine should be concentrated unless there are other diseases that affect sodium or urea concentrations which may result in medullary washout. Ranges assigned to USG include hyposthenuria (<1.008) and isosthenuria (1.008-1.012). Isosthenuria indicates that kidney has not diluted or concentrated the urine since it entered the glomerulus. Hyposthenuria suggests the kidney has diluted the urine. It is Isosthenuria that we have been classically concerned about in animals with renal failure. However, what is most important to consider is if the USG is appropriate for the hydration status. On the urine dipstick the presence of protein, in dilute urine, with an inactive sediment can be an excellent indicator of renal disease. Both tubular and glomerular lesions can result in proteinuria long before the patient is azotemic. Proteinuria may be the first indicator of renal disease. A urine protein-to-creatinine ratio (or UPC) can be very beneficial in taking into account the patient’s glomerular filtration rate and comparing it to the excretion of protein. If a patient has persistent proteinuria with an inactive sediment, it is useful to follow up with a UPC. Within the urine sediment, the presence of casts can indicate renal lesions. The classification of the casts- granular, cellular, hyaline-can help to indicate the cause and the significance.

Evaluation of renal function is multifactorial. There are many analytes that are useful in the diagnosis of disease. No one test is all-encompassing.