Determination of glomerular filtration rate (GFR) - i.e., the volume of ultrafiltrate produced per unit of time - is considered to be the gold standard to evaluate kidney function. Glomerular filtration rate is mostly estimated by plasma clearance of a filtration marker. Appropriate filtration markers are freely filtered through the glomerulus, not protein-bound, not toxic, do not undergo tubular secretion or absorption, and do not alter GFR.^1,2

The most important rationale to assess GFR in feline medicine is to facilitate early detection of CKD allowing more timely therapeutic intervention and possibly an improved prognosis. Therefore, assessment of GFR might be valuable for cats with one or more risk factor(s) for CKD (e.g., age, breed, related condition, drug therapy), particularly if routine diagnostic tests give doubtful or conflicting results or for cats with a clinical suspicion of CKD that cannot be confirmed with routine diagnostic tests. Routine diagnostic tests (serum urea, serum creatinine, urine specific gravity [USG]) have important limitations to diagnose feline CKD. Serum urea and creatinine concentrations are insensitive markers that increase late in the disease process, and cats with early CKD often retain their urine concentrating ability. These limitations can be partly overcome by measurement of symmetric dimethylarginine (SDMA), a new and promising indirect marker of GFR. SDMA exceeds the reference interval earlier in the disease process than serum creatinine, and persistently increased SDMA confirms kidney dysfunction, even in non-azotemic cats.³ Further, measurement of GFR is recommended in order to accurately dose potentially toxic drugs that primarily undergo renal excretion.

Scientific reports mostly describe multi-sample plasma clearance of inulin, iodinated contrast agents (mostly iohexol) or creatinine administered by single intravenous injection to estimate feline GFR. Unfortunately, these methods have important limitations for routine practical use. At first, multi-sample techniques for GFR estimation are labor-intensive, time-consuming and may be stressful or painful for the patient, particularly in cats. Secondly, iohexol and inulin assays are not widely available and injectable creatinine is not commercially available. Thirdly, GFR reference intervals are poorly reported for healthy cats, necessitating to design laboratory-specific reference intervals.

To increase practical usefulness, efforts have been taken to simplify GFR determination through the design of limited sampling strategies (LSSs), namely clearance techniques based on a reduced number of blood samples. These LSSs should be a suitable compromise between practical convenience and clinical accuracy for GFR estimation. Multiple approaches have been published, but for many of these LSSs no or only few renal-impaired cats were evaluated and the reference GFR used to design the LSS often had limitations. One group recently published a single sample method for estimating feline GFR in both non-azotemic and azotemic cats.⁴ Secondly, our research group recently developed LSSs in a cat population with wide range of GFR using a noncompartmental approach to compute GFR and starting from a reference GFR based on multiple blood samples over a 10-hour period. Using this methodology, at least 3 or 4 blood samples after injection of the clearance marker were needed to estimate GFR with an acceptable margin of error.⁵ Further research is necessary to determine which LSS gives the most accurate GFR estimate and is suitable for daily practical use.

In humans, GFR is estimated from prediction equations that take into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. These equations are more reliable than estimates of GFR from measurement of serum creatinine alone, mainly because they compensate for the substantial variation in creatinine production across sex, age and ethnicity.⁶ Similarly, the endogenous creatinine production rate has a high inter-individual variability in cats,⁷ but which factors (e.g., age, breed, sex) are responsible for this variation and whether GFR can be reliably estimated based on serum creatinine and demographic variables are currently unknown.

Alternatively, our research group developed two simple and cost-effective methods to identify cats with borderline or low GFR, without the need to determine the actual GFR value of the cat. The first method uses a regression formula based on routine variables including serum creatinine, serum urea, USG and urinary protein:creatinine ratio and predicts decreased GFR with high sensitivity and moderate-to-good specificity. The second method compares the clearance marker concentration at 60, 120 or 180 minutes after marker injection with a cut-off concentration. The higher the clearance marker concentration above the proposed cut-off, the more likely the cat has decreased kidney function.⁵

References

1.  Braun JP, Lefebvre HP. Kidney function and damage. In: Kaneko JJH, Harvey JW, Bruss ML, editors. Clinical Biochemistry of Domestic Animals. 6th ed. London, UK: Elsevier; 2008:485–528.

2.  Von Hendy-Willson VE, Pressler BM. An overview of glomerular filtration rate testing in dogs and cats. Vet J. 2011;188:156–165.

3.  Hall JA, Yerramilli M, Obare E, et al. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med. 2014;28:1676–1683.

4.  Finch NC, Heiene R, Elliott J, et al. A single sample method for estimating glomerular filtration rate in cats. J Vet Intern Med. 2013;27:782–790.

5.  Paepe D, Lefebvre HP, Concordet D, et al. Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate. J Feline Med Surg. 2015;17:889–900.

6.  National Kidney Foundation (NKF). K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39:S1–S266.

7.  Le Garreres A, Laroute V, De La Farge F, et al. Disposition of plasma creatinine in non-azotemic and moderately azotemic cats. J Feline Med Surg. 2007;9:89–96.