Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein, and retinol-binding protein as early biomarkers of chronic kidney disease in dogs.

Camila Rodrigues,Dennis Chew,Cínthia Martorelli,Jose Manuel C. Capcha,Fernanda Chacar,Douglas Caragelasco,Talita R. Sanches,Lúcia Andrade,Márcia Kogika

doi:10.14814/phy2.13262

Camila Rodrigues, Dennis Chew + Show 7 more

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https://doi.org/10.14814/phy2.13262

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Abstract

Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein‐to‐creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS‐PAGE and western blotting to determine the expression of albumin, vitamin D‐binding protein (VDBP), retinol‐binding protein (RBP), and Tamm‐Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (n = 9); and dogs with CKD (n = 40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (P ≤ 0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (P ≤ 0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

Highlights

The optimal evaluation of proteinuria includes quantitative and qualitative assays
Tubules make up approximately 90% of the renal cortical mass and that proximal tubule injury can lead to fibrosis, glomerulosclerosis, and chronic kidney disease (CKD) (Grgic et al 2002), we evaluated whether sensitive, specific markers of proximal tubule injury—vitamin D-binding protein (VDBP) and retinol-binding protein (RBP)—can identify CKD in dogs
According to the International Renal Interest Society (IRIS) guidelines, borderline proteinuria is defined as a urinary protein-to-creatinine ratio (UP/C) within the 0.2–0.5 range (IRIS 2015)

Summary

Introduction

The urinary protein-to-creatinine ratio (UP/C) provides information only about the magnitude of proteinuria, not about its origin. The severity of CKD is characterized by determining the serum creatinine level, which allows the glomerular filtration rate to be estimated, and the degree of albuminuria, which is generally accepted as a measure of glomerular permeability. These biomarkers reflect the filtration and barrier functions of the kidney glomeruli, small albuminuria can result from tubule dysfunction (Russo et al 2007).

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