Renal ultrasonographic shear-wave elastography and urinary procollagen type III amino-terminal propeptide in chronic kidney disease dogs

Abstract

Background and aim: Renal fibrosis is a well-established pathological alteration associated with chronic kidney disease (CKD) in several species and progresses as CKD advances. Although a renal biopsy is the gold standard for determining renal fibrosis, it is an invasive, impractical method for clinical practice. In humans, ultrasonographic shear-wave elastography (SWE), a novel advanced diagnostic imaging tool, can evaluate renal parenchyma stiffness, and urinary procollagen type III amino-terminal propeptide (uPIIINP), a promising renal fibrosis biomarker in humans, has increasingly been use applied to reduce the biopsies. This study compares renal tissue elasticity observed through SWE Young's modulus (E) values between healthy dogs (HD) and those with CKD.

Materials and methods: The E value acquired by SWE, uPIIINP levels, and renal function were evaluated in 15 CKD dogs and 15 HD.

Results: The renal cortical E values were significantly higher than the renal medullary E values in both groups (p<0.001). Renal cortical and medullary E values in CKD dogs were significantly higher than in HD (p<0.01). Cortical E values had greater significant correlations with renal functional parameters than the medullary E values and had a significant positive correlation with concentrations of plasma creatinine (Cr) (p<0.001); blood urea nitrogen (p<0.01); urine protein Cr ratio (p<0.01); and fractional excretions of sodium (p<0.05), potassium (p<0.05), chloride (p<0.05), and magnesium (p<0.001) while they had a negative correlation with urine specific gravity (p<0.05) and urine osmolality to plasma osmolality ratio (p<0.05). The uPIIINP to Cr (uPIIINP/Cr) ratios of CKD dogs were higher than those of HD (p<0.001). Moreover, the uPIIINP/Cr levels presented significant correlations with the renal cortical E values (p<0.01) and also the renal functional parameters.

Conclusion: SWE offers a complementary, non-invasive diagnostic imaging tool for evaluating renal tissue stiffness in CKD dogs with renal function deterioration. In addition, uPIIINP levels are associated with renal function and structural changes in dogs. Therefore, the uPIIINP level might be a non-invasive, complementary, and promising biomarker for evaluating renal fibrosis in canine CKD.

Keywords: chronic kidney disease; dog; renal fibrosis; shear-wave elastography; urinary procollagen type III amino-terminal propeptide.

Figure-1

B-mode ultrasound images (a and c) and color quantitative elastogram superimposed on the B-mode with regions of interest (b and d) between a healthy dog (A and B) and a chronic kidney disease dog (c and d).

Figure-2

The average renal E values of cortex and medulla (mean±SD) within group and between groups of dogs; the healthy dogs and chronic kidney disease group. Statistical difference between the average renal E values of cortex and medullar within each group using Paired t-test; comparison between the average renal E values of cortex between groups using Unpaired t-test; comparison between the average renal E values of medulla between groups using Mann–Whitney test. ***p<0.001; **p<0.01.

Figure-3

Box and whisker plot illustrating the uPIIINP/Cr ratios between groups using Mann–Whitney test; (a) the uPIIINP/Cr ratios between the HD and chronic kidney disease (CKD) dogs; (b) the uPIIINP/Cr ratios between CKD dogs with IRIS Stages 2 and 3. uPIIINP/Cr=Urinary procollagen type III amino-terminal propeptide to creatinine ratio, IRIS=The International Renal Interest Society staging system.

Figure-4

Correlation between average renal cortical E values from shear-wave elastography and uPIIINP/Cr of 30 dogs. Correlation was made using Spearman correlation coefficient. E=Young’s modulus values, uPIIINP/Cr=Urine Procollagen Type III N-Terminal Propeptide to creatinine.