Improving renal function in dogs and cats with chronic renal failure (CRF) is often not possible inasmuch as the renal lesions and associated dysfunction are usually irreversible and progressive.
Diagnostic testing offers new options for detecting patients in the early stages of renal disease. An annual examination, that includes a complete blood count serum biochemistry and urinalysis, is a good method for detecting renal function.
Unfortunately, due to the large functional renal reserve and the compensatory hypertrophy of remaining nephrons, clinical signs and laboratory data compatible with renal failure are not present until greater than 75-85 percent of all nephrons are nonfunctional. Once CRF is established, management options are limited and usually directed at reducing clinical signs and attempting to slow disease progression.
Early detection of renal disease, prior to the onset of failure, should improve our ability to alter the course of the disease.
Most CRF, unless the underlying lesions are familial, occurs in middle- to older-aged dogs and cats. An annual health examination, that includes a complete blood count, serum biochemistry profile, and urinalysis, is one of the best ways to detect declining renal function (Table 1). Special attention should be paid to decreases in appetite, body weight, packed cell volume, and urine specific gravity.
Table 1: Historical, clinicopathologic findings that may be associated with early renal disease in dogs and cats
Conversely, increases in serum urea nitrogen, creatinine, and phosphorus, or urinary excretion of protein may signal the onset of renal disease. Plotting the inverse of the serum creatinine concentration versus time can demonstrate a decrease in renal excretory function (Table 2,). Dogs and cats may also become more susceptible to bacterial urinary tract infections as their ability to concentrate urine decreases and the antibacterial properties of their urine decrease. If any of the above parameters suggest the possibility of renal disease, an ultrasound examination should be used to evaluate kidney tissue architecture. Pyelectasia (dilatation of the renal pelvis compatible with pyelonephritis) (Photo 1), renoliths (Photo 2), and renal cortical fibrosis can be demonstrated by ultrasound. Percutaneous or ultrasound-guided renal biopsy can be used to confirm or further define renal cortical disease.
Table 2: A hypothetical 1/serum creatinine concentration vs. time curve demonstrating declining renal function.
Azotemia and glomerular filtration rate
Azotemia is defined as increased concentrations of urea and creatinine in the blood. The interpretation of serum urea nitrogen and creatinine concentrations as a measure of renal function requires a knowledge of the production and excretion of these substances. Urea is synthesized in the liver from ammonia, which is in turn generated from the catabolism of ingested and endogenous proteins. Urea production is increased in the settings of high dietary protein intake and upper gastrointestinal tract hemorrhage. Conversely, urea production is decreased in the settings of a low dietary protein intake, decreased hepatic function, or decreased delivery of ammonia to the liver (e.g., portosystemic shunt). Urea nitrogen is excreted by glomerular filtration. Subsequent tubular reabsorption of urea nitrogen decreases the amount excreted by returning the waste product to the blood stream.
Photo 1: Ultrasound image from a canine kidney demonstrating dilatation of the renal pelvis (pyelectasia) compatible with pyelonephritis. (Courtesy of Dr. David Biller, Kansas State University).
Tubular reabsorption of urea is increased when tubular flow rates and volumes are decreased. Conversely, the tubular resorption of urea is decreased and excretion increased in the presence of diuresis.
Creatinine is formed by the nonenzymatic metabolism of creatine and phosphocreatine in muscle. Creatinine production is relatively constant and proportional to muscle mass; animals with a large muscle mass produce more creatinine each day than do animals with a small muscle mass. In comparison with the urea nitrogen, the creatinine concentration is relatively unaffected by the dietary protein level; however, serum creatinine concentrations can increase after the ingestion of meat and subsequent increased absorption of creatinine from the gastrointestinal tract. Creatinine is excreted via glomerular filtration.
Photo 2: Ultrasound image from a canine kidney demonstrating a renouroliths. (Courtesy of Dr. David Biller, Kansas State University).
Serum urea nitrogen and creatinine concentrations provide a crude index of the glomerular filtration rate (GFR). Inasmuch as the creatinine concentration is influenced by fewer extrarenal variables and creatinine is not resorbed by the renal tubules, the serum creatinine concentration is a better index of GFR than the serum urea nitrogen. Nevertheless, azotemia resulting from impaired renal function is not detectable until relatively late in the disease process. Therefore measurement of GFR can provide more accurate information about renal excretory function than the serum creatinine and urea nitrogen concentrations, especially early in renal disease before 75-85 percent of the nephrons are nonfunctional.
Plasma clearance of iohexol, an iodinated radiographic contrast agent, can provide a reliable estimate of GFR in dogs and cats. After a single, intravenous injection of iohexol, plasma clearance of the substance is calculated as the quotient of the administered dose divided by the area under the plasma concentration versus the time curve. The area under the plasma concentration versus the time curve is determined from several plasma iohexol concentrations obtained after the initial injection. The plasma clearance of iohexol is then correlated with exogenous creatinine clearance by linear regression analysis.
Calculation of iohexol clearance does not require urine collection so the procedure is less labor intensive and invasive compared with creatinine clearance techniques. Plasma concentrations of iohexol can be measured and GFR calculated at specialized reference laboratories.
Renal scintigraphy using technetium 99m–labeled compounds also allows the GFR to be evaluated and is available at many university teaching hospitals and major referral centers. This is a quick noninvasive method that does not require urinary catheterization and has the advantage of being able to quantitatively evaluate individual kidney function. Disadvantages of this procedure include its limited availability, exposure of the animal to radioisotopes, and the need for radioisotope disposal.