Differentiation of stable kidney function versus progressive dysfunction in dogs

Abstract

Background: Circulating creatinine and symmetric dimethylarginine (SDMA) are biomarkers of kidney function that have been used variously to define stable vs progressive chronic kidney disease (CKD). Slope monitoring of inverse biomarker values (creatinine^-1 or SDMA^-1 ) has shown promise, but quantitative criteria to distinguish stable vs progressive CKD using this approach are lacking.

Objective: Assessment of creatinine^-1 and SDMA^-1 slope cutoffs to distinguish stable vs progressive CKD.

Animals: One hundred ten clinically healthy university staff-owned dogs and 29 male colony dogs with progressive X-linked hereditary nephropathy (XLHN).

Methods: Retrospective analysis combining 2 prospective observational studies, 1 tracking kidney function biomarkers in healthy dogs (HDs) to a maximum of 3 years, and 1 tracking kidney function biomarkers in male colony dogs with progressive XLHN to a maximum of 1 year. The minimum slope of creatinine^-1 or SDMA^-1 as measured using the IDEXX SDMA test from HD was assigned as the slope cutoff for stable kidney function.

Results: The stable vs progressive slope cutoff was -0.0119 week × dL/mg for creatinine^-1 and -0.0007 week × dL/μg for SDMA^-1 .

Conclusions and clinical importance: In the studied CKD population, progressive dysfunction can be distinguished from stable kidney function by using the slope of creatinine^-1 or SDMA^-1 . These criteria may serve to characterize CKD in other cohorts of dogs and to establish guidelines for degrees of progression rate in dogs with naturally occurring CKD.

Keywords: biomarker; creatinine; disease monitoring; inverse slope; symmetric dimethylarginine.

FIGURE 1

Progression plots for CREA and CREA⁻¹ in HD and XLHN study groups. The progression of (A) CREA and (B) CREA⁻¹ values over time are shown for each dog. All XLHN dogs (n = 29) are shown. However, only 30 HD selected at random are shown because of space considerations. CREA, creatinine; HD, healthy dogs; XLHN, X‐linked hereditary nephropathy.

FIGURE 2

Progression plots for SDMA and SDMA⁻¹ in HD and XLHN study groups. The progression of (A) SDMA and (B) SDMA⁻¹ values over time are shown for each dog. All XLHN dogs (n = 29) are shown. However, only 30 HD selected at random are shown because of space considerations. HD, healthy dogs; SDMA, symmetric dimethylarginine; XLHN, X‐linked hereditary nephropathy.

FIGURE 3

Radial plots of inverse biomarkers for HD and XLHN dogs. Inverse biomarker slopes for each dog were calculated using least squares regression. (A) CREA⁻¹ and (B) SDMA⁻¹ slopes were used to generate lines originating from a common y‐intercept chosen arbitrarily. The visualization of lines representing each dog provides a relative comparison of how inverse biomarker slopes differ for HD (blue) and XLHN (red) dogs. Lines generated from the dog with the median slope for each group are represented by dashed lines. The thick, solid gray line represents the stable vs progressive cutoff based on the minimum inverse biomarker slope of healthy dogs. CREA, creatinine; HD, healthy dogs; SDMA, symmetric dimethylarginine; XLHN, X‐linked hereditary nephropathy.

FIGURE 4

Boxplot of CREA⁻¹ and SDMA⁻¹ slopes for each HD and XLHN dog. Inverse biomarker slopes of individual dogs are shown. Slopes of HD were indistinguishable from zero (P > .7) whereas slopes of XLHN dogs were less than zero (P < .0001). Dashed lines represent the cutoff values for each inverse biomarker slope. CREA, creatinine; HD, healthy dogs; SDMA, symmetric dimethylarginine; XLHN, X‐linked hereditary nephropathy.