Urinary cystatin B differentiates progressive versus stable IRIS Stage 1 chronic kidney disease in dogs

Abstract

Abstract Background Early identification of dogs with progressive vs stable chronic kidney disease (CKD) might afford opportunity for interventions that would slow progression. However, currently no surrogate biomarker reliably predicts CKD progression. Hypothesis/Objectives Urinary cystatin B (uCysB), a novel kidney injury biomarker, predicts progressive disease in International Renal Interest Society (IRIS) CKD Stage 1. Animals Seventy‐two dogs, including 20 dogs from 4 university centers with IRIS CKD Stage 1, with IDEXX symmetric dimethylarginine (SDMA) concentration up to 17 μg/dL and no systemic comorbidities, and 52 clinically healthy staff‐owned dogs from a fifth university center. Methods A multicenter prospective longitudinal study was conducted between 2016 and 2021 to assess uCysB concentration in IRIS CKD Stage 1 and control dogs. Dogs were followed to a maximum of 3 years (control) or 25 months (CKD). Stage 1 IRIS CKD was classified as stable or progressive using the slope of 1/SDMA, calculated from 3 timepoints during the initial 90‐day period. Dogs with slope above or below −0.0007 week × dL/μg were classified as stable or progressive, respectively. Mixed effects modeling was used to assess the association between uCysB and progression rate. Results Estimates of first visit uCysB results predictive of active ongoing kidney injury based on the mixed effects models were 17 ng/mL for control, 24 ng/mL for stable CKD, and 212 ng/mL for progressive CKD (P < .001). Conclusions and Clinical Importance Urinary cystatin B differentiated stable vs progressive IRIS CKD Stage 1. Identification of dogs with progressive CKD may provide an opportunity for clinicians to intervene early and slow progression rate.

Keywords

• biomarker
• creatinine
• disease monitoring
• inverse slope
• symmetric dimethylarginine