Objective—To determine whether cats in the nonazotemic stages of chronic kidney disease have increased plasma parathyroid hormone (PTH) concentrations as a compensatory physiologic mechanism to maintain plasma phosphate concentration within the reference interval.
Design—Prospective longitudinal study.
Animals—118 client-owned geriatric cats with various degrees of renal function.
Procedures—For each cat, a blood sample was obtained for plasma biochemical analysis and determination of plasma PTH concentration, and a urine sample was obtained for determination of urine specific gravity at study entry (baseline) and after 12 months. For a subset of 30 cats, plasma calcitriol concentration was determined at baseline. Cats were categorized into 1 of 3 groups on the basis of kidney function at the end of 12 months. At baseline and after 12 months, plasma concentrations of variables associated with calcium homeostasis were compared between the 3 groups and also within groups over time. Multivariable linear regression was used to identify variables associated with plasma PTH concentration.
Results—Plasma PTH concentration was significantly increased in cats that developed azotemia, compared with PTH concentration in cats that remained nonazotemic, and PTH concentration increased before changes in plasma calcium and phosphate concentrations were detected. A moderate positive association between plasma calcitriol and PTH concentrations was identified. Plasma PTH concentration was associated with age and plasma urea, creatinine, and total calcium concentrations in the final multivariable model.
Conclusions and Clinical Relevance—Results suggested that renal secondary hyperparathyroidism can develop prior to azotemia in cats, even in the absence of hyperphosphatemia and hypocalcemia.
Objective—To determine prevalence of systolic
hypertension and associated risk factors in cats with
chronic renal failure evaluated in first-opinion practice.
Animals—103 cats with chronic renal failure.
Procedure—Systolic arterial blood pressure (SABP)
was measured with a noninvasive Doppler technique,
and cats that had SABP > 175 mm Hg on 2
occasions or that had SABP > 175 mm Hg and compatible
ocular lesions were classified as hypertensive.
Information from the history (previous treatment
for hyperthyroidism, age), physical examination
(sex, body weight), routine plasma biochemical
analyses (creatinine, cholesterol, potassium, sodium,
chloride, and calcium concentrations), and thyroid
status were evaluated as potential risk factors for
systolic hypertension. Variables associated with systolic
hypertension were evaluated by use of logistic
Results—20 (19.4%; 95% confidence interval, 13 to
28%) cats had systolic hypertension. Plasma potassium
concentration was significantly and inversely
associated with systolic hypertension.
Conclusions and Clinical Relevance—Prevalence of
systolic hypertension, although clinically important,
was lower than that reported previously. The cause of
the inverse association between systolic hypertension
and plasma potassium concentration is not yet
known. (J Am Vet Med Assoc 2002;220:1799–1804)
Objective—To compare concentrations of urinary iodide (UI) in euthyroid and untreated hyperthyroid cats.
Animals—118 euthyroid and 88 hyperthyroid client-owned cats from 2 nonreferral veterinary practices.
Procedures—Iodide concentration was measured in 5 urine samples collected every 3 to 12 months from selected cats, and variability of results between euthyroid cats and hyperthyroid cats prior to the diagnosis of hyperthyroidism was evaluated via 1-way ANOVA, after logarithmic transformation of UI concentrations (logUIs). The UI concentration in hyperthyroid cats was measured at diagnosis and 2 to 6 weeks and 3 to 6 months after treatment for hyperthyroidism. The pretreatment logUI in hyperthyroid cats was compared with that in euthyroid cats, taking into account the effects of renal function on UI concentration. Iodine intake was estimated in euthyroid cats following calculation of the volume of daily urine output, with a fixed value for iodine concentration in feces.
Results—The variability of UI concentrations did not differ significantly between hyperthyroid (n = 10) and euthyroid (8) cats. The logUI increased 2 to 6 weeks after initiation of treatment in hyperthyroid cats (n = 80) and was lower in azotemic versus nonazotemic cats. Hyperthyroid cats had a lower logUI than euthyroid cats, and there was no evidence of deficient iodine intake in euthyroid cats.
Conclusions and Clinical Relevance—The logUI was lower in cats with azotemia and with untreated hyperthyroidism, compared with that in euthyroid cats from the same population. Additional studies are needed to determine whether iodine intake plays a role in the development of hyperthyroidism in cats.
Objective—To validate a nonautomated technique for the measurement of urinary N-acetyl-β-D-glucosaminidase (NAG) activity in cats and assess the correlation between NAG index, plasma creatinine concentration, and proteinuria.
Animals—197 client-owned cats (≥ 9 years old; 119 neutered males and 78 neutered females) of which 103 had previously been determined to have chronic kidney disease (CKD).
Procedures—Preliminary assay validation was performed for a nonautomated colorimetric technique for quantification of NAG activity. The effect of storage of samples was examined. A cross-sectional study was performed to assess urinary NAG index in cats with variable plasma creatinine concentrations and with proteinuria, as quantified by use of the urine protein-to-creatinine ratio (UP:C).
Results—Interassay coefficients of variance (CVs) in cats with low (mean, 0.64 U/L), medium (mean, 4.38.U/L), and high (mean, 8.48 U/L) urine NAG activity were 25.9%, 14.4%, and 25.1%, respectively, but intra-assay CVs were < 20%. Urine NAG activity was stable for 4 freeze-thaw cycles and for storage at −20°C. There was no significant difference in log NAG index when cats (n = 197) were grouped according to plasma creatinine concentration, but a moderate positive correlation was found between log NAG index and log UP:C (r2 = 0.259).
Conclusions and Clinical Relevance—N-acetyl-β-D-glucosaminidase activity can be quantified in feline urine by use of a nonautomated colorimetric technique. However, data should be interpreted cautiously because of high interassay CVs. The NAG index in cats with CKD may be indicative of ongoing lysosomal activity rather than active proximal tubular cell damage.
Objective—To evaluate urine cauxin immunoreactivity in geriatric cats with variable plasma creatinine concentrations and proteinuria and to assess urinary cauxin-to-creatinine concentration ratio (UC/C) as a predictor of developing azotemia.
Animals—188 client-owned geriatric (≥ 9 years of age) cats.
Procedures—A direct immunoassay was developed and validated for the quantification of urinary cauxin relative to a standard curve generated from a urine sample with high cauxin immunoreactivity. Relationships among UC/C, plasma creatinine concentration, and proteinuria were assessed. Nonazotemic cats were recruited and followed for 12 months. Urinary cauxin-to-creatinine concentration ratio was evaluated as a predictor of development of azotemia in these cats.
Results—No relationship was evident between UC/C and plasma creatinine concentration. A weak positive correlation was identified between UC/C and urine protein-to-creatinine concentration ratio (r = 0.212). At entry to the longitudinal study, those cats that later developed azotemia had a UC/C that was significantly higher than in those remaining nonazotemic after 12 months.
Conclusions and Clinical Relevance—The UC/C did not vary with severity of azotemia but appeared contributory to the feline urinary proteome. High UC/C values were predictive of the geriatric cats in our study developing azotemia. However, it seems unlikely that UC/C will provide additional information about the measurement of urine protein-to-creatinine concentration ratio as a biomarker for the development of azotemia in cats.
Objective—To evaluate proteomic delineation of feline urine by mass spectrometry as a method for identifying biomarkers in cats at risk of developing azotemia.
Samples—Urine samples from geriatric cats (> 9 years old) with chronic kidney disease and nonazotemic cats that either remained nonazotemic (n = 10) or developed azotemia (10) within 1 year.
Procedures—Optimization studies with pooled urine were performed to facilitate the use of surface enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for analysis of the urinary proteome of cats. Urine samples from nonazotemic cats at entry to the study were analyzed via SELDI-TOF-MS with weak cation exchange and strong anion exchange arrays. Spectral data were compared to identify biomarkers for development of azotemia.
Results—Low protein concentration in feline urine precluded direct application to array surfaces, and a buffer exchange and concentration step was required prior to SELDI-TOF-MS analysis. Three preparation conditions by use of weak cation and strong anion exchange arrays were selected on the basis of optimization studies for detection of biomarkers. Eight potential biomarkers with an m/z of 2,822, 9,886, 10,033, 10,151, 10,234, 11,653, 4,421, and 9,505 were delineated.
Conclusions and Clinical Relevance—SELDI-TOF-MS can be used to detect urinary low-molecular weight peptides and proteins that may represent biomarkers for early detection of renal damage. Further study is required to purify and identify potential biomarkers before their use in a clinical setting.
Objective—To develop a formula for correcting slope-intercept plasma iohexol clearance in cats and to compare clearance of total iohexol (TIox), endo-iohexol (EnIox), and exo-iohexol (ExIox).
Animals—20 client-owned, healthy adult and geriatric cats.
Procedures—Plasma clearance of TIox was determined via multisample and slope-intercept methods. A multisample method was used to determine clearance for EnIox and ExIox. A second-order polynomial correction factor was derived by performing regression analysis of the multisample data with the slope-intercept data and forcing the regression line though the origin. Clearance corrected by use of the derived formula was compared with clearance corrected by use of Brochner-Mortensen human and Heiene canine formulae. Statistical testing was applied, and Bland-Altman plots were created to assess the degree of agreement between TIox, EnIox, and ExIox clearance.
Results—Mean ± SD iohexol clearance estimated via multisample and corrected slope-intercept methods was 2.16 ± 0.35 mL/min/kg and 2.14 ± 0.34 mL/min/kg, respectively. The derived feline correction formula was Clcorrected = (1.036 × Cluncorrected) – (0.062 × Cluncorrected2), in which Cl represents clearance. Results obtained by use of the 2 methods were in excellent agreement. Clearance corrected by use of the Heiene formula had a linear relationship with clearance corrected by use of the feline formula; however, the relationship of the feline formula with the Brochner-Mortensen formula was nonlinear. Agreement between TIox, EnIox, and ExIox clearance was excellent.
Conclusions and Clinical Relevance—The derived feline correction formula applied to slope-intercept plasma iohexol clearance accurately predicted multisample clearance in cats. Use of this technique offers an important advantage by reducing stress to cats associated with repeated blood sample collection and decreasing the costs of analysis.
Objective—To determine whether amlodipine besylate
decreases systemic arterial blood pressure (BP)
and reduces the prevalence of complications in cats
with induced hypertensive renal insufficiency.
Animals—20 cats with partial nephrectomy.
Procedure—Following reduction in renal mass, 10
cats were administered 0.25 mg of amlodipine/kg,
PO, q 24 h (group A). Ten cats served as a control
group (group C). Systolic BP (SBP), diastolic BP (DBP),
and mean BP (MBP), physical activity, and pulse rate
were measured continuously for 36 days by use of
Results—Compared with values for clinically normal
cats, SBP, DBP, and MBP were significantly increased
in cats of group C. Cats in group A had significant
reductions in SBP, DBP, and MBP, compared with values
for cats in group C. Albuminuria but not urine protein-
to-creatinine ratio was significantly correlated
( R2 = 0.317) with SBP in hypertensive cats.
Prevalence of ocular lesions attributable to systemic
hypertension in group C (7 cats) was greater than that
observed in group A (2). Two cats in group C were
euthanatized on day 16 because of nuerologic complications
attributed to systemic hypertension. One normotensive
cat in group A was euthanatized because
of purulent enteritis of unknown cause on day 27.
Conclusion and Clinical Relevance—Amlodipine
had an antihypertensive effect in cats with coexistent
systemic hypertension and renal insufficiency. Its use
may improve the prognosis for cats with systemic
hypertension by decreasing the risk of ocular injury or
neurologic complications induced by high BP. (Am J
Vet Res 2002;63:833–839)