Page 743 - Small Animal Clinical Nutrition 5th Edition

Chronic Kidney Disease 771

(Finco et al, 1993). However, in cats, exogenous creatinine
VetBooks.ir clearance does not accurately estimate GFR (Finco et al, 1996).
In addition, factors other than GFR (e.g., hydration status) can
affect creatinine clearance and serum creatinine concentration.
Clearance of iohexol, a readily available radiographic contrast
medium, has been used to reliably estimate GFR in dogs and
cats and is a convenient method that can be used in clinical
practice (Finco et al, 2001; Miyamoto 2001, 2001a; Goy-
Thollot et al, 2006; Sanderson, 2009).

Altered Membrane Permselectivity
Proteinuria is the hallmark of altered glomerular membrane
permselectivity. In patients with glomerular disease, permselec-
tive properties of the glomerular capillary wall are altered and
increased amounts of protein are present in urine. Glo-
merulopathies are the most common cause of severe (heavy)
proteinuria in dogs and cats although they appear to be more
common in dogs than cats. Glomerulopathies can be primary Figure 37-1. The relationship between serum creatinine concentra-
(e.g., renal amyloidosis in dogs or idiopathic membranous tion and % of normal glomerular filtration rate (GFR) or % of remain-
ing functional nephrons is not linear. Therefore, small changes in GFR
nephropathy) or secondary to systemic infectious, inflammato-
during early chronic kidney disease do not result in increased serum
ry or neoplastic diseases (e.g., lupus erythematosus, heartworm
creatinine concentrations. Notice that values for serum creatinine do
disease, ehrlichiosis, lymphoma). not exceed the upper reference range (broken line) until kidney dys-
Proteinuria is defined as excretion of greater than normal function is marked (i.e., when 75% of nephrons are nonfunctional).
amounts of protein in urine. Potential causes include urinary
tract hemorrhage or inflammation, tubular resorptive defects,
“overflow” proteinuria and altered glomerular permselectivity. canine and feline albuminuria was 69 and 31%, respectively.
Clinical significance of proteinuria depends on its severity Therefore, 31 and 69% of dogs and cats, respectively, with a
and persistence. In the absence of hyperproteinemia, hema- positive dipstick reaction for protein did not have proteinuria.
turia and urinary tract inflammation, persistent proteinuria Based on this, false positive reactions are common, especially in
usually indicates kidney disease and severe proteinuria (urine cats, and may occur with concentrated or alkaline urine, hema-
protein-creatinine ratio [UPC] ≥2) is generally associated turia, pyuria, urine contaminated with quaternary ammonium
with glomerular disease. The magnitude of proteinuria does compounds or with excessive urine contact time with the dip-
not predict reversibility of the underlying disease, however. stick pad (Grauer et al, 2004). Observer variation is a docu-
Serial quantitative evaluation of proteinuria is necessary for mented and unavoidable source of error with dipstick tests. All
prognosis and assessment of response to treatment. Clinicians positive dipstick reactions for proteinuria should be followed up
should confirm the persistence of proteinuria and attempt to with additional testing such as the SSA test or testing for
localize its source before performing invasive and expensive microalbuminuria (Lees et al, 2005). The SSA test is used by
diagnostic tests such as renal biopsy. Significance of protein- most commercial laboratories and can be performed in-house
uria should always be interpreted in context of other labora- by mixing equal volumes of centrifuged urine and 5% SSA, a
tory and clinical findings (e.g., microscopic urine sediment available from chemical supply companies. Resulting turbidity
examination). of urine is graded on a scale of 0 (no turbidity) to 4+ (complete-
Qualitative techniques for measurement of proteinuria ly opaque). Microalbuminuria can be detected in-house using a
include dipstick methods and precipitation techniques such as species-specific point-of-care test. b
the sulfosalicylic acid (SSA) test. Urine concentration (refrac- In patients with stable renal function, the UPC ratio is a
tive index, specific gravity) should be considered when inter- semiquantitative method for assessing proteinuria. The UPC
preting results of these qualitative techniques (Finco, 1995). ratio is calculated by dividing urinary protein concentration by
The most commonly used qualitative test is the colorimetric urinary creatinine concentration. Urinary protein is measured
dipstick test. The test depends on ability of proteins, especially by a quantitative analytical technique rather than by dipstick. It
albumin, to alter the color reaction in paper impregnated with may be determined in commercial laboratories or by using an
c
a pH-sensitive dye, tetrabromophenol blue. The test pad is in-house kit. Because urinary excretion of creatinine and pro-
buffered so that color changes reflect changes in protein con- tein is presumed constant in the presence of stable GFR, the
centration. In one study, sensitivity of the urine protein test UPC ratio in a single urine sample can be used to estimate 24-
strip for albuminuria in canine and feline urine was 54 and hour urinary protein loss.The time of day and method of urine
60%,respectively.This means that 46 and 40% of dogs and cats, sample collection are not critical.The UPC ratio eliminates the
respectively, had proteinuria that was not detected by the dip- potentially confounding effect of urine concentration on inter-
stick (Grauer et al, 2004). Urine protein test strip specificity for pretation of urinary protein concentration. A UPC ratio less