Page 454 - WSAVA2017
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An Urban Experience
IRIS CKD staging is based currently on fasting blood creatinine concentrations, but there are indications
that SDMA concentrations in blood plasma or serum may be a more sensitive biomarker of renal function. Accordingly, if blood SDMA concentrations are known, some modification to the guidelines might be considered, as follows:
• A persistent increase in SDMA above 14 μg/dl suggests reduced renal function and may be a reason to consider a dog or cat with creatinine values in IRIS CKD Stage 1 range
• In IRIS CKD2 patients with low body condition scores, SDMA ≥25 μg/dl may indicate degree of renal dysfunction has been underestimated. Consider treatment recommendations for IRIS CKD3.
• In IRIS CKD3 patients with low body condition scores, SDMA ≥45 μg/dl may indicate degree of renal dysfunction has been underestimated. Consider treatment for IRIS CKD4.
IRIS CKD1 is a non-azotemic dog or cat with kidney disease. There are several potential types of patient:
- Patients with proteinuria consistent with primary glomerular disease
- Patients without proteinuria that is consistent with primary glomerular disease such as bilateral renal disease, but no biochemical abnormalities (e.g. renal infarcts, nephroliths) or patients with unilateral renal disease that may or may not be serious (e.g. unilateral renal lymphoma, unilateral renal agenesis, unilateral nephrolithiasis)
The diagnosis of CKD1 disease is, therefore, dependent on finding renal disease that is chronic in nature but associated with a normal creatinine concentration.
The urine may or may not be concentrated. The use
of SDMA determination may help; however, SDMA may be normal with serious unilateral renal disease (e.g. unilateral renal lymphoma) as with creatinine, BUN, and USG. Additionally, comorbidities complicate patients with CKD including those in stage 1 (e.g. feline hyperthyroidism, urinary tract infections, etc).
Glomerular filtration rate (GFR) can be estimated using both clearance methods and “spot” or single time point tests. Renal or plasma clearance of an injected substance (e.g., iohexol, creatinine) is most accurate estimate of GFR. It is more sensitive means for detecting early CKD than spot methods of GFR estimation. Determining plasma clearance can be a relatively expensive and time-consuming procedure. It is most often performed
to establish a decrease in GFR when clinical parameters (e.g., poorly concentrated urine) create suspicion for CKD but cannot confirm its presence, and to determine
dosage regimens for therapeutic agents whose excretion is primarily renal in patients with CKD. Measuring reduction of an injected substance in the blood over time) can be used to estimate renal clearance and therefore GFR. Most common exogenous substances used in veterinary medicine for estimation of GFR are iohexol
and creatinine. Other substances and techniques can be used, such as inulin, radiolabeled markers, and contrast- enhanced computed tomography (CT). A novel fluorescent tracer has been evaluated as a rapid, non-invasive bedside test in dogs. Ultimately, choice in method used depends on availability of the injected substance and method of measurement as well as the experience. In some cases, estimation of individual kidney GFR (vs. global GFR) is necessary, as is possible with scintigraphy or CT. Iohexol clearance and exogenous creatinine clearance give a measure of total GFR; DTPA (a radiolabelled marker) gives estimate of total as well as individual kidney GFR. One of the main limitations with clearance methods is need for serial, precisely timed blood draws. An accurate clearance calculation requires as many as 8 post-injection blood samples over 6 hours or longer, although reasonable estimates can be obtained with limited sampling (i.e.,
2 or 3 post-injection samples). Timing of these limited sample collections varies depending on the substance used. Some studies have found that calculation of plasma clearance based on a single post-injection sample is strongly correlated with 3-sample techniques, as long as an estimated volume of distribution can be determined. This is especially important in cats, where multiple collections can prove difficult. Another limitation with plasma clearance is the large amount of variability in what is considered to be “normal” in dogs and cats. In one study of 118 healthy dogs, iohexol clearance ranged from 0.95-4.25 mL/min/kg. In previously published studies in healthy dogs and cats, the range for various clearance estimates was as wide as 2.45-6.64 mL/min/kg (dogs) and 2.19-3.49 mL/min/kg (cats), although most weighted reference intervals were around 3-4 mL/min/kg (dogs) and 2.5-3.5 mL/min/kg (cats). Therefore, it is difficult
to define a normal GFR in a particular animal without a baseline for that patient, and it limits ability of plasma clearance to detect early reductions in GFR. Week-to- week and month-to-month biological variability must also be considered when monitoring plasma clearance in a particular patient. Based on the week-to-week variability of iohexol clearance in a cohort of dogs with mild but stable renal disease, a subsequent measurement must increase or decrease by up to 20% in order to be 95% confident that a true change in clearance has occurred. Interestingly, despite using more measurements, each with its own inherent variability, iohexol clearance variability was similar to that for serum creatinine (sCr) in these dogs. In addition to biological considerations, analytical considerations in plasma clearance calculations are important. When using a limited sampling technique, a correction formula must be applied to correct for the initial distribution phase in order

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