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to avoid overestimation of the GFR. Correction formulas for both dogs and cats are available when using iohexol. Normalization to body weight, surface area, or extracellular volume has been recommended, but it is not clear which normalization technique should be used in dogs and cats.
In patients with CKD1 disease, azotemia is not present and a spot test such as urine specific gravity (USG)
may not reflect renal function because it is influenced
by non-renal factors. Most adult cats have a USG > 1.035 regardless of time of day whereas adult dogs have variable USG throughout the day. Persistently
dilute USG may indicate loss of renal function but other non-renal diseases (e.g. hyperadrenocorticism, diabetes, mellitus, hyperthyroidism, etc) must be ruled out first. Other biomarkers are being evaluated. Symmetric dimethylarginine (SDMA) test is now provided on all biochemical panel testing through IDEXX Laboratories: SDMA
is a small molecule that originates from hydrolysis
of methylated proteins. This molecule has shown
great promise as an endogenous marker of GFR as
it appears to be exclusively eliminated by glomerular filtration, and significant extra-renal influences on its production and elimination have not yet been identified. It is stable in whole blood, serum, and plasma at 4oC and room temperature for up to 7 days, and it is not altered with freezing in serum or plasma.(3) In dogs with rapidly progressing CKD, SDMA correlated strongly with GFR estimated using iohexol clearance. Notably, when using reference intervals, SDMA identified a decrease in GFR earlier than sCr, however, when
both were trended over time, no major differences
in identification of declining GFR were noted. SDMA changed approximately 9 months earlier than sCr. These results support that trending of sCr is necessary for sensitive detection of decreasing GFR and that SDMA might be a useful adjunct to sCr in identification of renal disease, particularly given the tendency to classify a
dog as azotemic or not based on a reference interval. SDMA is not influenced by muscle mass, but any non- renal change in GFR will impact it. For example, with dehydration there is a decrease in GFR and therefore SDMA will also be influenced. It might prove especially useful in the initial diagnosis of CKD in those patients
for which sCr will not provide a reliable estimate of GFR. In cats with CKD, SDMA correlates with sCr. While
data suggest that SDMA might increase beyond its reference interval before sCr in cats and that a higher SDMA:creatinine ratio might indicate a worse prognosis. Similar to dogs, it is not influenced by lean body mass; however, non-renal factors affecting GFR will impact SDMA. SDMA changed approximately 17 months earlier than sCr.
An Urban Experience
Most publications discuss management of IRIS CKD2- 4, where therapy has been shown to improve survival and quality of life in dogs and cats. There is minimal information on prognosis and management of patients diagnosed with IRIS CKD1, and most information applies to patients with proteinuric CKD1 disease.
Overt glomerular proteinuria occurs more commonly
in dogs than in cats and is defined as a urine
protein creatinine ratio (UPC) > 2.0 that is renal in
origin. Approximately 50% of dogs with glomerular proteinuria have an immune-mediated disease either
as a primary process or secondary to chronic antigenic stimulation (e.g. infections, inflammatory, or neoplastic disease).(4) Treatment involves achieving a diagnosis
of the underlying cause, if possible, and treating it, if possible. Other treatment involves feeding a protein restricted diet (therapeutic renal diet), giving omega-3 fatty acids (300 mg of sum of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) per 10 pounds
of body weight per day), and pharmacologic agents
that inhibit the renin-angiotensin-aldosterone system (RAAS).(5) Conventionally, an angiotensin converting enzyme inhibitor (ACEI) is often used and has the most, albeit, limited data. Enalapril has been evaluated in
dogs with glomerular proteinuria and was shown to decrease the degree of proteinuria and increase the serum albumin concentration. Benazepril is often used instead of Enalapril; however, there is one study in dogs comparing Enalapril with benazepril in dogs with CKD and proteinuria and Enalapril gave a more sustained anti- proteinuric effect over 5 months. Angiotensin receptor blockers (ARB) may be used in combination with or instead of ACEI although there is minimal information available. In human beings, use of an ACEI with an
ARB provides better proteinuria lowering response than either alone. This has not been evaluated in dogs. While Losartan is the oldest of the ARBs, newer ARBs, such as Telmisartan and Irbesartan, have more selectivity for the angiotensin receptor and may have a greater effect. With any RAAS inhibitor potential adverse events include azotemia, hyperkalemia, and GI disturbances. ACEI
are usually administered every 12 hours while ARB
are usually administered every 24 hours. Dogs with glomerular proteinuria are often administered drugs that inhibit platelet aggregation (e.g. aspirin or clopidogrel). In dogs with a diagnosis of an immune mediated disease by renal biopsy, in dogs with suspected immune-mediated glomerulonephritis, or in dogs that do not respond well
to conventional therapy, immunosuppression should
be undertaken. Which imusuppressive drug is best is
not known. None have been shown to be effective in controlled studies, although there are sporadic case

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