Comparison of Multistix PRO dipsticks with other biochemical assays for determining urine protein (UP), urine creatinine (UC) and UP:UC ratio in dogs and cats

BACKGROUND: Urine protein: urine creatinine (UP:UC) ratio determined from the quantitative measurement of protein and creatinine in a single urine sample is the best feasible assessment of clinically significant proteinuria in dogs and cats. A dipstick that measures urine protein, urine creatinine, and UP:UC ratio has been used in human medicine and could have application for veterinary practice. OBJECTIVE: The objective of this study was to compare the Multistix PRO dipstick (Bayer Corporation, Elkhart, IN, USA) to other biochemical methods for determination of urine protein and creatinine, and UP:UC ratio in canine and feline urine. METHODS: A complete urinalysis, including sulfosalicylic acid (SSA) precipitation, was performed on urine samples submitted to our laboratory between February and April 2003 from 100 dogs and 49 cats. Urine protein and creatinine concentrations were determined by the Multistix PRO dipstick using a Clinitek 50 analyzer (Bayer) and compared with the results of SSA precipitation and quantitative biochemical analysis. The UP:UC ratios from the dipstick results (calculated by the Clinitek 50 and also manually) were compared with those calculated from quantitative values. Pearson product-moment correlation analysis and diagnostic sensitivity and specificity (using quantitative results as the gold standard) were determined. RESULTS: For both canine and feline urine, protein and creatinine concentrations determined by the Multistix PRO correlated closely with quantitative concentrations for protein (dogs r = .78, P = .0001; cats r = .87, P = .0001) and creatinine (dogs r = .78, P = .0001; cats r = .76, P = .0001). The Multistix PRO was more sensitive and less specific than SSA precipitation for diagnosing clinically significant proteinuria. UP:UC ratios obtained by manual calculation of dipstick results correlated best with quantitative UP:UC ratios in dogs, and had higher specificity but lower sensitivity for the diagnosis of proteinuria. In cats, UP:UC ratios determined by the dipstick method did not correlate (r = -.24, P = .0974) with quantitative values. CONCLUSIONS: The Multistix PRO, with manual calculation of UP:UC, may be a good alternative for the diagnosis of clinically significant proteinuria in dogs, but not cats. Dipstick creatinine concentration should be considered as an estimate.     

Comparison of a semiquantitative point-of-care assay for the detection of canine microalbuminuria with routine semiquantitative methods for proteinuria

Background: It has been speculated that renal disease can be identified through the detection and quantification of microalbuminuria, however, reliable measurement of albuminuria in any quantity can be challenging. Recently, a new point‐of‐care immunoassay was validated for the specific detection of microalbuminuria and early renal disease in dogs. Objectives: The goal of this study was to determine if measurement of microalbuminuria by the point‐of‐care immunoassay correlated with results from routine semiquantitative methods for detecting proteinuria in dogs. Methods: One hundred and thirty‐eight urine samples, from 133 different dogs, submitted for urinalysis to the Clinical Pathology Laboratory at the University of Missouri‐Columbia Veterinary Medical Teaching Hospital were eligible for the study. Samples that contained >20 RBC/high power field (hpf) or >20 WBC/hpf were excluded, as were samples with insufficient volume to complete all tests. All samples were evaluated with a urinary dipstick with or without a sulfosalicylic acid turbidimetric test, a urine protein:creatinine (UPC) ratio, and the immunoassay for microalbuminuria. Data were analyzed by the Spearman rank order correlation. Results: Microalbuminuria results correlated significantly with those of the dipstick (r= 0.715), sulfosalicylic acid test (r= 0.742), and UPC ratio (r= 0.830). Correlation between the immunoassay and UPC ratio was the same (r= 0.830) when only samples with trace or 1+ proteinuria by dipstick were analyzed (n = 51). Conclusions: The point‐of‐care immunoassay results for microalbuminuria correlated with the results of semiquantitative methods for detecting total proteinuria in dogs. Routine methods for canine proteinuria appear to be adequate for determining whether further testing for renal disease is warranted.     

Evaluation of the effect of urine dip vs urine drip on multi‐test strip results

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in‐clinic laboratory tests. No independent, evidence‐based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe.     

Prevalence of positive urine culture in the presence of inactive urine sediment in 1049 urine samples from dogs

BackgroundUrinalysis (UA) is often used to screen for bacterial cystitis, regardless of sediment results, and followed up by quantitative urine culture (UC) for definitive diagnosis.ObjectivesDetermine prevalence of positive UCs in dogs with inactive urine sediments on routine UA.AnimalsA total of 1049 urine samples with inactive urine sediments and UCs collected from dogs presented to a veterinary specialty hospital between January 2018 and February 2020.MethodsRetrospective study of dogs with an inactive urine sediment on routine UA and follow‐up UCs. Signalment, UA findings, proteinuria, and UC results were recorded. Associations among these findings were assessed using multivariate logistic regression carried out using a backward stepwise method.ResultsOverall prevalence of positive UC was 3.4% (95% confidence interval [CI], 2.4‐4.8). Escherichia coli was the most commonly isolated bacteria. Only naturally voided samples were associated with increased prevalence of positive culture when compared to collection by cystocentesis or a non‐specified method. No statistically significant association with culture positivity was found for urine protein‐to‐creatinine ratio, urine specific gravity, urine pH, breed, age, or sex.Conclusions and Clinical ImportanceBased on the low prevalence (3.4%) of positive culture in urine samples from dogs with inactive sediment on routine UA and the relatively high cost of UC and sensitivity, cost‐benefit analysis including clinical suspicion of lower urinary tract disease should inform testing decisions, rather than routinely performing cultures on urine samples without active sediments.     

Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

BackgroundAn imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.ObjectivesTo examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.AnimalsTwenty dogs with CKD and 10 healthy dogs.MethodsIn this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.ResultsSerum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs.Conclusions and Clinical Importanceleptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.     

Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease

Background

Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs.

Objectives

We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD.

Methods

We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined.

Results

Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage.

Conclusions and clinical importance

Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD.     

Comparison of three types of analyzers for urine protein-to-creatinine ratios in dogs

BackgroundQuantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR).ObjectivesThis study aimed to compare the UPCR obtained by three types of analyzers (automated wet chemistry analyzer, in-house dry chemistry analyzer, and dipstick reading device) and investigate whether the differences could affect clinical decision process.MethodsUrine samples were collected from 115 dogs. UPCR values were obtained using three analyzers. Bland-Altman and Passing Bablok tests were used to analyze agreement between the UPCR values. Urine samples were classified as normal or proteinuria based on the UPCR values obtained by each analyzer and concordance in the classification evaluated with Cohen''s kappa coefficient.ResultsPassing and Bablok regression showed that there were proportional as well as constant difference between UPCR values obtained by a dipstick reading device and those obtained by the other analyzers. The concordance in the classification of proteinuria was very high (κ = 0.82) between the automated wet chemistry analyzer and in-house dry chemistry analyzer, while the dipstick reading device showed moderate concordance with the automated wet chemistry analyzer (κ = 0.52) and in-house dry chemistry analyzer (κ = 0.53).ConclusionsAlthough the urine dipstick test is simple and a widely used point-of-care test, our results indicate that UPCR values obtained by the dipstick test are not appropriate for clinical use. Inter-instrumental variability may affect clinical decision process based on UPCR values and should be emphasized in veterinary practice.