GFR was measured by iohexol clearance, with a result of 3.1 ml/kg/min (reference range = 2.89 to 8.07 ml/kg/min). Based on
these normal results, a water deprivation test was performed. Belle's urine specific gravity increased to 1.031 within 10
hours, and psychogenic polydipsia was diagnosed. The owner was instructed on behavior modification techniques to decrease
stress and advised that some water restriction would be safe. The owners declined therapy for the cystic calculi. Two years
later, Belle presented for an unrelated problem and was noted to have a urine specific gravity of 1.050.
A boxer with chronic PU/PD. Ali, a 10-year-old spayed female boxer, presented for evaluation of polyuria and polydipsia of 12 months' duration that had
gotten progressively worse over the previous three months. Her BUN concentration was 11 mg/dl, creatinine concentration was
0.8 mg/dl, and urine specific gravity was 1.004.
ACTH stimulation test results and fasting and postprandial bile acid concentrations were normal. No abnormalities were seen
on an abdominal ultrasonographic examination. During a water deprivation test, when Ali had lost 5% of her body weight, her
urine specific gravity was still 1.020. Urine concentration did not increase after administration of antidiuretic hormone.
GFR was measured by iohexol clearance to exclude renal insufficiency. The result was 4.932 ml/kg/min, well within the reference
range. Nephrogenic diabetes insipidus was diagnosed, and chlorothiazide therapy was initiated.
A Westie with a history of acute renal failure. Nico, a 6-year-old castrated male West Highland white terrier, was presented for a follow-up evaluation. He had a history
of acute renal failure associated with pyuria two years previously. His azotemia had resolved completely. He remained polyuric
since that episode, with urine specific gravity measurements ranging between 1.010 and 1.027.
On a routine recheck, microalbuminuria was noted, and the owner requested testing to determine if Nico had chronic kidney
disease. The benefits of renal biopsy to determine if structural changes were present were discussed with the owner as well
as GFR measurement to determine whether functional changes were present. The result of GFR measurement by iohexol clearance
was 6.95 ml/kg/min and indicated that renal function had returned to normal after the pyelonephritis episode. No renal therapy
was prescribed. Biannual urinalysis, urine protein concentration determination, and serum chemistry profile testing and annual
GFR measurement were recommended to monitor Nico for renal disease progression.
EXOGENOUS CREATININE CLEARANCE
While the exogenous creatinine clearance test is generally less accurate than iohexol clearance in animals with reduced GFR
or with fewer than six sampling points, it has the advantage of providing results rapidly after completion of the test.2 In this test, exogenous creatinine (60 mg/kg) is administered intravenously. Many different protocols exist for the timing
of obtaining the blood samples after injection, but, in general, at least three samples are needed, and the last sample should
be at least six hours after the injection. The protocol I use includes blood sampling immediately before creatinine administration
and 10, 60, 240, 360, and 600 minutes after administration. The serum creatinine concentration results, which can be obtained
through standard laboratories, are used to calculate the GFR.
Creatinine is safe to administer intravenously and does not induce signs of uremia. Injectable-grade creatinine is not readily
available commercially but can be obtained through some specialty pharmacies that will custom-formulate preparations from
chemical-grade creatinine. Royal Canin has developed a software program to calculate the GFR for creatinine clearance.4,5 (For a copy, e-mail the author at Cathy.firstname.lastname@example.org
Case example: Exogenous creatinine clearance in a young Mastiff with renal dysplasia
Exogenous creatinine clearance was performed in Annie, a 1-year-old female Mastiff with renal dysplasia. Because the 10-hour
sample had such a high creatinine concentration (Table 1), Annie was presented again the next day for a 24-hour sample. Creatinine clearance was 0.6 ml/kg/min, which is markedly
below the reference range of 2 to 4.5 ml/kg/min. By the following week, the serum creatinine concentration had decreased to
the baseline at 7.2 mg/dl. Annie was enrolled in a drug study at that time. Three months later, her baseline serum creatinine
concentration was 9.9 mg/dl and her GFR measured by creatinine clearance had dropped to half of the initial value—0.3 ml/kg/min.
She was euthanized two months later because of progressive signs of uremia.
Table 1: Annie's Exogenous Creatinine Clearance Results