Day‐to‐Day Variation of the Urine Protein: Creatinine Ratio in Female Dogs with Stable Glomerular Proteinuria Caused by X‐Linked Hereditary Nephropathy

Abstract

Background: Interpretation of serial urine protein : creatinine (UPC) values is confounded by a lack of data regarding random biologic variation of UPC values in dogs with stable glomerular proteinuria.Hypothesis: That there is minimal day-to-day variability in the UPC of dogs with unchanging proteinuria and the number of measurements needed to reliably estimate UPC varies with the magnitude of proteinuria.Animals: Forty-eight heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) causing stable proteinuria.Methods: Urine samples were obtained daily by cystocentesis for 3 consecutive days on 183 occasions (549 samples). The UPC was measured for each sample with a single dry-film chemistry auto-analyzer. Data were analyzed retrospectively by a power of the mean model because the variance of UPC values within the 3-day evaluation periods increased as the magnitude of proteinuria increased.Results: To demonstrate a significant difference (P , .05) between serial values in these proteinuric dogs, the UPC must change by at least 35% at high UPC values (near 12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably estimate the UPC when UPC ,4, but 2-5 determinations are necessary at higher UPC values.Conclusions and Clinical Importance: These guidelines for interpretation of serial UPC values in female dogs with XLHN may also be helpful for interpretation of UPC values in dogs with other glomerulopathies.

Comparison of Single, Averaged, and Pooled Urine Protein:Creatinine Ratios in Proteinuric Dogs Undergoing Medical Treatment

“…When monitoring dogs with proteinuria, it is recommended that the UPC must change by 80% at lower UPC (near 0.5) and by at least 35% at higher UPC (near 12) to be considered clinically relevant . When assessing agreement between single UPC and pooled UPC in our study, we found that single UPC could differ from the pooled UPC by <15 or >51%.…”

“…If the baseline UPC was 8.0, then depending on the method used, the subsequent UPC could be between 7.83 and 10.4. According to a previous study, this result also would not be considered clinically relevant because the results only differ by 2–30%, respectively. Therefore, the difference in UPC between the 2 methods would be acceptable in dogs with lower or higher UPC results.…”

“…Monitoring dogs with proteinuria can be challenging because of day‐to‐day variation in their UPC results, making it difficult to know what changes are clinically relevant. One study of a colony of female research dogs found that a single measurement reliably estimated the UPC when UPC was <4 but indicated that 2–5 measurements are necessary when the UPC is higher . This study evaluated a homogenous research colony in a controlled laboratory setting and did not evaluate the biologic variability in the UPC in client‐owned dogs, which could be affected by a variety of factors in an uncontrolled natural setting.…”

Proteinuria in Apparently Healthy Elderly Dogs: Persistency and Comparison Between Free Catch and Cystocentesis Urine

“…In 4 cases (10%), dogs switched to a higher classification on the consecutive sample, not explained by the sediment. There is daily variation in UPC values . To indicate disease progression or adequate treatment response, differences in UPC have to be >80% at a UPC near 0.5 .…”

“…There is daily variation in UPC values . To indicate disease progression or adequate treatment response, differences in UPC have to be >80% at a UPC near 0.5 . In the dogs with inconsistent consecutive UPC categories, a variance of >80% was only seen in 1 sample (switching from no proteinuria to overt proteinuria).…”