Cathy E. Langston, DVM, DACVIM
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Serum creatinine concentration is a commonly used marker of renal function because of its simplicity, availability, and cost.
Unfortunately, it is an insensitive marker of renal function, in that the glomerular filtration rate (GFR) must be 75% below
normal for the creatinine concentration to be elevated.
As an alternative, measuring the GFR can be useful in numerous situations commonly encountered in practice, such as
- Evaluating patients with polyuria without azotemia to definitively exclude or diagnose kidney disease as the underlying cause
- Monitoring renal function in patients with early kidney disease (i.e. annual testing) to evaluate the efficacy of therapy
- Monitoring for further kidney injury in patients with suspected nonazotemic kidney disease that must receive nephrotoxic drugs
(e.g. chemotherapeutics, aminoglycoside antibiotics)
- Evaluating patients in which nephrectomy is being considered (i.e. renal neoplasia).
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Not all methods of GFR measurement are practical for private practice. Tests that require urine collection over a specified
time are prone to error from incomplete recovery of urine because of urinary catheterization problems. However, plasma clearance
techniques involve obtaining multiple blood samples without urine sampling. The basic premise behind these tests involves
an intravenous injection of a substance that is freely filtered by the glomerulus and is not further excreted or reabsorbed
by the renal tubules or cleared or metabolized by other organs. The rate of disappearance from the bloodstream indicates the
plasma clearance. Multiple plasma markers and test protocols have been investigated, and no optimal protocol has been identified,
but some methods of GFR measurement such as iohexol clearance and exogenous creatinine clearance can be readily performed
in private practice with sufficient accuracy for clinical decision-making. In addition, patients in which nephrectomy is being
considered may be referred for renal scintigraphy to measure the GFR of each kidney.
IOHEXOL CLEARANCE
In this test, 300 mg/kg of iohexol, a commonly used radiographic contrast agent, is administered intravenously, and blood
samples are typically drawn two, three, and four hours later.1,2 The timing of sample collection is flexible, but the exact time the samples were drawn needs to be accurately recorded so
the precise time elapsed since injection can be calculated. The most commonly used veterinary diagnostic laboratory that offers
measurement of iohexol concentrations and calculated GFR is Michigan State University's Diagnostic Center for Population &
Animal Health (animalhealth.msu.edu/Submittal_Forms/AD.ADM.FORM.017.pdf), and results are generally available within a week.
Other radiographic contrast agents such as iothalamate cannot be substituted for iohexol because the assay specifically measures
iohexol and does not detect iothalamate. Although iodine allergic reaction or development of mild reversible acute kidney
failure has been reported in people undergoing this type of test, the risk in animals appears to be low.3
Case examples: Iohexol clearance
The next four brief case examples reveal how measuring GFR with the iohexol clearance test was a valuable tool in patient
management.
A senior Rhodesian ridgeback with PU/PD. Sheba, a 10-year-old spayed female Rhodesian ridgeback, was evaluated because of polyuria and polydipsia. Her blood urea nitrogen
concentration (BUN) was 15 mg/dl (reference range = 7 to 27 mg/dl), creatinine concentration was 1.5 mg/dl (reference range
= 0.4 to 1.8 mg/dl), and urine specific gravity was 1.005. Urine bacterial culture results were negative, the urine cortisol:creatinine
ratio was normal, and the urine protein:creatinine ratio was 0.1 (reference range < 0.5). No abnormalities were seen on an
abdominal ultrasonographic examination.
Her GFR was measured by iohexol clearance, with a result of 1.635 ml/kg/min, which is a 70% reduction from the expected mean
of 5.48 ml/kg/min, confirming IRIS Stage I chronic kidney disease (iris-kidney.com/pdf/IRIS2009_Staging_CKD.pdf). Inadequate
urine concentration tends to occur with over 66% reduction in GFR, whereas azotemia occurs with over 75% reduction.
A renal diet was initiated. One month later, hypertension was diagnosed, so benazepril and amlodipine were prescribed. Nine
months later, Sheba remains clinically stable.
A senior dog with PU/PD and cystic calculi. Belle, an 11-year-old spayed female mixed-breed dog, was presented for evaluation of polyuria and polydipsia. Her BUN concentration
was 12 mg/dl, creatinine concentration was 1 mg/dl, and urine specific gravity was 1.018. ACTH stimulation test results were
normal, as were fasting and postprandial bile acid concentrations. An abdominal ultrasonographic examination revealed cystic
calculi. The owner was unsure if there had been a partial improvement in the polydipsia after a course of antibiotics.
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