Flaws in Traditional Tests for Renal Function
Urine concentrating ability is impaired when 66% of nephrons are no longer functioning, and azotemia develops when 75% of
nephrons are no longer functioning. However, many variables not related to renal function can affect urine concentrating ability,
blood urea nitrogen (BUN) and serum creatinine (SCr). In addition, the relationship between GFR and BUN, SCr is not linear.
Early in renal disease, large decreases in GFR cause only small increases in BUN and SCr, while in advanced renal disease,
small changes in GFR result in large changes in BUN and SCr. This occurs because the insidious loss of nephrons occurring
with CRF is initially accompanied by compensatory hypertrophy of residual functional nephrons so that their single-nephron
GFR may more than double, resulting in enhanced excretion of nitrogenous wastes and delay of onset of azotemia until more
nephrons are lost. These findings indicate that patients are often worse off in terms of number of functional nephrons than
surmised by considering BUN and SCr values. This interpretation and the abundance of non-renal influences on urine concentration,
BUN and SCr, provides a strong argument for pursuing more sensitive methods for evaluating renal function
More Sensitive Tests for Detecting Renal Dysfunction
Reciprocal of Serum Creatinine (1/SCr) versus Time
It has been suggested by some investigators that plotting the 1/SCr vs time shows a linear decrease in renal function with
time, and it is an accurate method of following progression of renal disease. Other studies have suggested that this method
often gives erroneous estimates of rates of progression because a perfect linear correlation between 1/SCr and GFR does not
always occur. Therefore although the 1/SCr vs time is commonly used to assess GFR, the accuracy of this test is in question.
Plasma Clearance Tests
GFR is defined as mls of plasma that are cleared of a substance/min/kg BW. Renal clearance assays are used to define GFR by
determining clearance of a plasma-borne solute from urine. Examples include:
1. Inulin or isotope clearance is considered the "gold standard" for estimating GFR. Performing this test is labor intensive,
requires continuous infusion of inulin and arduous laboratory measurements, making this technique impractical for routine
use in clinical practice.
2. Radionucleides and nuclear imaging techniques is an alternative method for calculating GFR. However, specialized equipment
and handling of radioactive materials is required, and therefore use of this test is primarily limited to research settings,
and it is impractical for routine use in clinical practice.
3. Less precise alternatives include endogenous or exogenous creatinine clearance. Both of these tests require accurately
performed timed urine collections. This entails intermittent catheterization of the urinary bladder, is labor intensive and
stressful and slightly invasive for the patient.
Alternative Test for Detecting Renal Dysfunction in Clinical Practice
Until recently, diagnosing early (pre-azotemic) renal disease in dogs and cats was primarily limited to renal clearance tests,
such as inulin or creatinine clearance. The inability to readily assess renal function in a practical way often posed a dilemma
for clinicians with patients whose only finding was a low urine specific gravity. As a result, detection of early (pre-azotemic)
renal disease was often missed. In addition, assessing renal function in patients with azotemic renal failure also has inherent
limitations, and relying solely on SCr and BUN levels was fraught with its own set of problems.
Iohexol Clearance Test
This test has been recently developed for use in dogs and cats. It is easy to perform, doesn't require any specialized equipment
or collection of urine, and therefore is practical for routine use in clinical practice. The relative ease of performing serum
clearance procedures, compared to urinary clearance procedures, also makes this test attractive.
Iohexol (Omnipaque®)
Is a low osmolar, nonionic, iodinated radiographic contrast medium used for radiographic procedures in both human and veterinary
medicine. By measuring disappearance of iodine in serum following a single IV dose of iohexol, GFR can be estimated [see end
of notes for the protocol for performing iohexol clearance].
