Association of microalbuminuria and the urine albumin-to-creatinine ratio with systemic disease in cats

OBJECTIVE: To determine the diagnostic usefulness of semiquantitative and quantitative microalbuminuria assays and urine albumin-to-creatinine (UAC) ratio for detecting disease in cats. DESIGN: Prospective study. ANIMALS: 441 cats evaluated at a veterinary teaching hospital. PROCEDURES: Urine samples from cats for which a complete medical record was available were included. Urine dipstick results, urine protein-to-creatinine ratios (cutoffs, 0.1 and 0.4), semiquantitative and quantitative microalbuminuria assay results (cutoff, 1 mg/dL), and UAC ratio values (cutoffs, 100 and 200 mg/g) were determined. Clinical diagnoses determined within 3 months of enrollment were recorded. Sensitivity and specificity were determined with disease status used as the standard. The influences of clinical diagnosis, sex, age, serum urea nitrogen and creatinine concentrations, blood pressure, bacterial urine culture results, rectal temperature, pyuria, hematuria, and bacteriuria were evaluated by means of logistic regression. RESULTS: Of 441 cats that were eligible for inclusion, 40 were healthy and 401 had > or = 1 disease. Results of logistic regression indicated that significant associations existed for age, presence of disease, presence of urinary tract disease, azotemia, hematuria, and pyuria and results of 1 or both of the microalbuminuria assays. CONCLUSIONS and CLINICAL RELEVANCE: Microalbuminuria was associated with underlying disease. Sensitivity and specificity of the microalbuminuria assays for detection of systemic disease were superior to those of other tests. Microalbuminuria testing in conjunction with other screening procedures may increase identification of occult disease. A prospective study evaluating the predictive values of screening tests with and without microalbuminuria determination is needed to validate this recommendation.     

Evaluation of the zetacrit and zeta sedimentation ratio in dogs

The Wintrobe erythrocyte sedimentation rate (ESR) has been used in animals and persons as a screening test for inflammatory disease and as a monitor for disease progression in individuals. Now, the zetacrit (ZC) and zeta sedimentation ratio (ZSR) are suggested as suitable rapid laboratory tests to replace the ESR in dogs. In 65 dogs, a strong inverse correlation between ESR and ZC was observed (r = -0.961, P less than 0.05). Significant correlations of similar magnitude between ZC and hematocrit (r = 0.587, P less than 0.05) and ESR and Hct (r = 0.569, P less than 0.05) were observed. In addition, influences of various protein fractions, such as fibrinogen, globulin, and albumin, on the ESR and ZC were evaluated and found to be of similar magnitude. These data indicate that ESR and ZC are equivalent methods for determining erythrocyte sedimentation rates in dogs. A strong correlation (r = 0.900, P less than 0.05) between Wintrobe ESR, adjusted for the effect of Hct (ESRHct), and ZSR was observed. The influence of plasma proteins on ESRHct and ZSR was of similar magnitude. However, a weak yet significant correlation between ESRHct and the microhematocrit remained (r = 0.291, P less than 0.05). Data indicate that the latter more effectively factors out the influence of Hct on sedimentation.     

Evaluation of association between body size and large intestinal transit time in healthy dogs

OBJECTIVE: To compare large intestinal transit time (LITT) in dogs of various body sizes and determine whether fecal quality was correlated with LITT. ANIMALS: 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: LITT was calculated as the difference between total (TTT) and orocecal transit time (OCTT). Minimum and mean OCTTs were determined by use of the sulfasalazine-sulfapyridine method. Minimum TTT was estimated by use of chromium and ferric oxide as color markers, and mean TTT was calculated from the recovery from feces of ingested colored plastic beads. Fecal moisture content was determined and fecal consistency was scored during the same period. RESULTS: Large-breed dogs had higher fecal moisture content and more watery fecal consistency. No association between body size and OCTT was detected, but there was a positive correlation between body size and mean TTT. Mean LITT increased significantly with body size, from 9.1 +/- 1.1 hours in Miniature Poodles to 39.4 +/- 1.6 hours for Giant Schnauzers. Significant correlations were detected among mean LITT, mean TTT, and fecal scores, whereas no correlation was observed between fecal moisture content and TTT or LITT. CONCLUSIONS AND CLINICAL RELEVANCE: LITT was correlated with fecal consistency in dogs of various body sizes. Mean LITT can be predicted from values for mean TTT in healthy dogs.     

Associations among systemic blood pressure,microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.     

Relationship between urine ammonium ion excretion and urine anion gap in dogs.

Acidemia stimulates renal ammonia production and excretion. This adaptive response allows increased H+ secretion and generation of new bicarbonate. To determine whether a relationship existed between urine ammonium (NH4+) concentration and excretion and urine anion gap (Na+ + K(+)- Cl-), ammonium chloride (NH4Cl) was administered per OS for 5 days to induce systemic acidemia in 12 healthy Beagles. During NH4Cl administration, a strong, statistically significant (P less than 0.0001) relationship was apparent between urine NH4+ concentration measured in millimoles per liter and urine anion gap. Regression equation: urine [NH4+] = 8.2 - 0.416 x urine anion gap; r = -0.897. A statistically significant (P = 0.0001) relationship existed between urine NH4+ excretion measured in millimoles per kilogram of body weight per day and urine anion gap. Regression equation: urine NH4+ excretion = 0.74 - 0.38 x urine anion gap; r = -0.768. As urine NH4+ concentration or excretion increased, urine anion gap became more negative. Before NH4Cl administration (no systemic acidemia), a weak, but statistically significant (P = 0.015) relationship was observed between urine NH4+ concentration and urine anion gap. Regression equation: urine [NH4+] = 65.2 - 0.141 x urine anion gap; r = -0.41. However, a relationship was not evident between urine NH4+ excretion and urine anion gap before NH4Cl administration. Hence, urine anion gap is a reliable index of urine NH4+ concentration and excretion only in dogs with metabolic acidosis. In human beings with distal renal tubular acidosis, NH4+ excretion is inappropriately low and results in a positive urine anion gap.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in dogs

OBJECTIVE: To evaluate 3 methods for measuring urine bile acids (UBA) and compare their diagnostic performance with that of the serum bile acids (SBA) test and other routine screening tests in dogs with hepatic disorders. DESIGN: Prospective study. ANIMALS: 15 healthy dogs, 102 dogs with hepatic disorders, and 9 dogs with clinical signs of hepatic disorders that were found to have nonhepatic disorders. PROCEDURES: Blood and urine samples were collected from sick dogs and healthy dogs for serum biochemical analyses, and determination of concentrations of SBA and UBA. Urine samples were obtained from 15 healthy dogs to establish an upper cutoff value for UBA concentrations. The UBA were measured by use of a quantitative-linked enzymatic colorimetric method. Three analytical modifications were evaluated; 1 quantified only urine sulfated bile acids (USBA), 1 only urine nonsulfated bile acids (UNSBA), and 1 quantified both (USBA plus UNSBA). The UBA values were standardized with the urine creatinine concentration. RESULTS: The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio tests had the best diagnostic performance of the UBA tests; each had a substantially higher specificity, slightly higher positive predictive value, slightly lower negative predictive value, and lower sensitivity than the SBA test. These UBA-to-creatinine values were positively correlated with SBA values. The USBA-to-creatinine ratio had poor sensitivity, indicating a low rate of bile acid sulfation in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The UBA can be measured in dogs with sufficient repeatability and accuracy for clinical application. The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio identified dogs with hepatic disorders nearly as well as the SBA test.     

Evaluation of the association between spondylosis deformans and clinical signs of intervertebral disk disease in dogs: 172 cases (1999-2000)

OBJECTIVE: To evaluate the association between spondylosis deformans and clinical signs of intervertebral disk disease (IVDD) in dogs. DESIGN: Retrospective case series. ANIMALS: 210 dogs. PROCEDURE: Records of 172 dogs with clinical signs of IVDD and 38 dogs with other neurologic disorders were reviewed. Signalment, sites of spondylosis, severity of associated osteophytosis, type of disk herniation, and duration of signs were recorded. RESULTS: Dogs with IVDD had significantly fewer sites of involvement and lower grades of spondylosis deformans, compared with those in the non-IVDD group. When groups were adjusted for age and weight via multivariate linear regression, there were no differences in severity of osteophytosis or number of affected sites. Dogs with type II disk disease had higher numbers of affected sites and more severe changes, compared with dogs with type I disk herniation. There was no difference between groups in the rate at which IVDD was diagnosed at sites of spondylosis, compared with the rate at which IVDD was diagnosed in unaffected disk spaces. Areas of spondylosis were closer to sites of IVDD that elicited clinical signs than to randomly chosen intervertebral spaces, and distances between sites of spondylosis and sites of IVDD had a bimodal appearance. CONCLUSIONS AND CLINICAL RELEVANCE: An association may exist between radiographically apparent spondylosis and type II disk disease; type I disk disease was not associated with spondylosis. Spondylosis in radiographs of dogs with suspected type I disk disease is not clinically important. Spatial associations among sites of spondylosis and sites of IVDD may be coincidental or associated with vertebral column biomechanics.     

Plasmapheresis in five dogs with systemic immune-mediated disease

Five dogs with signs referable to systemic immune-mediated disease, four with systemic lupus erythematosus, and one with probable lupus myopathy were treated with plasmapheresis in combination with low-dose immunosuppressive drug therapy. Previous treatment with conventional dosages of prednisone was not satisfactory and was associated with adverse side effects. Two dogs had short-term responses to combined therapy, and 3 dogs had sustained responses. Clinical remission was associated with normalization of serum complement levels and decreases in antinuclear antibody titers. Toxicosis potentially related to plasma component depletion was observed in 2 dogs. Acute clinical illness and disease states refractory to conventional immunosuppressive therapy should be considered indications for plasmapheresis.     

Comparison of semiquantitative test strips,urine protein electrophoresis,and an immunoturbidimetric assay for measuring microalbuminuria in dogs

Background: The presence of albumin in urine, even in small amounts, is always abnormal and usually reflects kidney dysfunction. Different techniques are commercially available for the measurement of microalbuminuria in dogs. Objectives: The purpose of this study was to compare the accuracy of semiquantitative test strips, urine protein electrophoresis, and a validated immunoturbidimetric assay in the measurement of microalbuminuria in dogs. Methods: Urine samples were collected from 307 dogs presented to The Queen's Veterinary School Hospital, University of Cambridge, for a variety of clinical conditions. Urine was collected by midstream free catch (193/307, 63%), cystocentesis (89/307, 29%), or catheterization (25/307, 8%). Routine urinalysis was performed on all samples. Albumin was measured by using semiquantitative test strips, by agarose gel electrophoresis, and by an automated immunoturbidimetric assay designed for human samples (considered as the gold standard). The latter was validated using a purified canine albumin standard. Results: The immunoturbidimetric assay had within‐assay and between‐assay coefficients of variation (CV) of 1.3% and 5.0%, respectively, overall recovery of 97.1%, and high linearity (r=.985). Of the samples with measurable albumin (>1.4 mg/L) by the immunoturbidimetric assay, 57/195 (29%) were negative for albumin using the semiquantitative test strips and 138/195 (71%) were positive. Urine protein electrophoresis (UPE) and immunoturbidimetric results had a concordance CV of 86%. Conclusions: UPE and semiquantitative test strips are less accurate than the automated immunoturbidimetric method for the measurement of albumin in canine urine.     

Use of urine albumin/creatinine ratio for estimation of proteinuria in cats and dogs

The clinical utility of the urine albumin/creatinine ratio (UAC) using a simplified analyzer for estimation of proteinuria was studied in cats and dogs. Measurement results for diluted feline and canine albumin standard solutions showed linearity. Although conversion formulas (y=1.28x+1.04 and y=1.67x+10.47 for cats and dogs, respectively) were necessary, urine albumin concentrations could be determined in both animals. In cats and dogs with proteinuria, the UAC changed parallel with the urine protein/ creatinine ratio (UPC), and the Log UAC and Log UPC were significantly correlated (r=0.803 (p<0.01) in cats, r=0.801 (p<0.01) in dogs). The UAC using an UAC analyzer could be used clinically as one of the basic in-hospital laboratory tests for estimation of proteinuria in cats and dogs.     

Evaluation of gamma-glutamyl transpeptidase-to-creatinine ratio from spot samples of urine supernatant, as an indicator of urinary enzyme excretion in dogs

gamma-Glutamyl transpeptidase activity was measured accurately in canine urine supernatant without gel filtration and was relatively stable at 4 C for at least 4 days after collection. The urinary gamma-glutamyl transpeptidase-to-creatinine ratio in spot samples was simple and quick to measure and was correlated with the 24-hour enzyme excretion. However, the usefulness of this ratio may be limited by within-day variation, and a questionable theoretical basis for its validity.     

Effect of collection time and exercise restriction on the prediction of urine protein excretion, using urine protein/creatinine ratio in dogs

Nonproteinuric and proteinuric dogs were studied to determine whether the urine protein/creatinine ratio from a 24-hour urine sample could be used to predict urine protein excretion. Urine protein/creatinine ratios estimated from urine produced during daylight hours and from that produced during nighttime hours were compared to determine whether time of sample collection influenced the prediction of the urine protein excretion value. Urine protein/creatinine ratios in urine from male dogs were compared with those from female dogs to determine whether sex had an influence on the value. Hospitalized and nonhospitalized dogs were used to determine the effect of exercise restriction. The urine protein/creatinine ratio varied significantly between healthy and proteinuric dogs (P = 0.0001). It was not influenced by collection period or sex. Animals not confined to hospital cages had a significantly lower urine protein/creatinine ratio than did hospitalized animals confined to a cage (P = 0.003).     

Evaluation of serum and urine 1,5-anhydro-D-glucitol and myo-inositol concentrations in healthy dogs

1,5-anhydro-D-glucitol (1,5AG) is a pyranoid polyol compound found in human circulating blood. Myo-inositol (MI) is a stereoisomer of inositol and serves as a precursor of inositol phospholipids. 1,5AG and MI are filtered by the glomerulus and almost completely reabsorbed through the renal tubules. However, under hyperglycemic conditions, reabsorption through the renal tubules is competitively inhibited because the structures of 1,5AG and MI resemble that of glucose. In this study, we investigated the kinetics of serum and urine 1,5AG and MI levels in healthy dogs. We demonstrated that 1,5AG and MI exist in canine serum and urine by gas chromatography-mass spectrometry. Under continuous hyperglycemic conditions, the serum 1,5AG concentration in healthy dogs decreased while the serum MI concentration remained unchanged. Urinary excretion of 1,5AG and MI increased significantly after blood glucose concentrations reached 200 to 220 mg/dl. A significant negative correlation was observed between serum 1,5AG and glucose concentrations during hyperglycemia. However, no significant correlation was observed between serum MI and glucose concentrations. In this study, we demonstrated that serum and urine 1,5AG and MI levels were changed by blood glucose concentrations. The serum 1,5AG concentration was decreased by continuous hyperglycemia. However, the serum MI concentration does not reflect hyperglycemia.