Plasma and urinary F₂-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease

Abstract

Objectives Oxidative stress contributes to chronic kidney disease (CKD) progression in humans and rodent models; F2-isoprostanes (F2-IsoPs) are established biomarkers of oxidative stress. Our primary aim was to evaluate plasma F2-IsoPs in cats with International Renal Interest Society stage 1 and 2 CKD, compared with healthy cats, and to determine whether plasma and urinary F2-IsoPs are equivalent biomarkers. The secondary aim was to assess whether consumption of a renal diet enriched in omega-3 fatty acids led to improvements in plasma and urinary F2-IsoPs. Methods Plasma and urinary F2-IsoPs were measured in 24 cats with stage 1 or 2 CKD, and 12 unaffected controls aged ⩾6 years. Twelve CKD cats were re-evaluated after feeding a commercial renal diet for at least 4 weeks. Results Median plasma F2-IsoPs were significantly higher in stage 1 CKD (96.2 pg/ml), early stage 2 CKD (83.2 pg/ml) and late stage 2 CKD (80.8 pg/ml) compared with healthy cats (22.8 pg/ml; P = 0.03−0.002). Median urinary F2-IsoPs were significantly higher in cats with stage 1 CKD (231.2 pg/mg) compared with healthy cats (152.5 pg/mg) or cats with late stage 2 CKD (124.8 pg/mg; P = 0.01). Plasma F2-IsoPs remained increased, while urinary F2-IsoPs fell with transition from stage 1 to stage 2 CKD. Feeding a commercial renal diet led to significant decreases in plasma F2-IsoPs in the small group of cats with stage 1 CKD (25−75% decrease) compared with cats with stage 2 CKD (20% decrease to 53% increase; P = 0.01). Conclusions and relevance Oxidative stress is prominent in cats with stage 1 CKD. Plasma and urinary F2-IsoPs are not interchangeable biomarkers in cats with stage 2 CKD. Placebo-controlled studies are indicated to evaluate dietary or pharmacologic doses of omega-3 fatty acids on redox stress and progression of renal dysfunction in cats with stage 1 CKD.

Urinary liver‐type fatty acid‐binding protein in clinically healthy elderly cats: Evaluation of its potential to detect IRIS stage 1 chronic kidney disease and borderline proteinuria

“…These combined recent data imply that renal pathological events exist in IRIS stage 1 feline CKD (Granick et al, 2020). In the present study, we did not find a difference in uL-FABP concentrations between cats with and without criteria of IRIS stage 1 CKD.…”

“…Urinary F2‐isoprostanes, biomarkers of oxidative stress, are also significantly increased in cats with IRIS stage 1 CKD compared to healthy cats. These combined recent data imply that renal pathological events exist in IRIS stage 1 feline CKD (Granick et al., 2020 ). In the present study, we did not find a difference in uL‐FABP concentrations between cats with and without criteria of IRIS stage 1 CKD.…”

“…Studies that investigated tubular biomarkers in cats with IRIS stage 1 CKD remain scarce (Granick et al., 2020 ; Maeda et al., 2015 ). Urinary transferrin and albumin concentrations are higher in cats with IRIS stage 1 CKD than in healthy cats (Maeda et al., 2015 ).…”

Oxidative Stress Contributes to Inflammatory and Cellular Damage in Systemic Lupus Erythematosus: Cellular Markers and Molecular Mechanism

“…Its process of formation, distinct structural properties, and relative chemical stability distinguish it from other radical-generated products, for which the measurement of plasma F2 isoprostane by MS/GC is contemplated to be the most reliable indicator of oxidative stress in vivo. 49 Elevated levels of F2 isoprostane have been attributed to tissue oxidation in SLE and therefore can be utilized as a marker to assess the relationship between mitochondrial function and oxidative stress in fatigued patients. 50 These metabolites establish covalent bonds to proteins, thereby enhancing their immunogenicity and prompting pathogenic autoantibodies to form.…”

8-Hydroxy-2′-deoxyguanosine and malondialdehyde in plasma and their association with disease severity in 20 cats with chronic kidney disease

“…As mentioned in the Introduction, oxidative stress is reportedly related to the deterioration of cats with CKD. 1,8,13,14 The evaluation of oxidative markers could have a deeper significance if there is an association between mortality and the levels of oxidative markers in cats, just as in humans. 7 In this study, 8-OHdG and MDA were identified as markers of oxidative stress.…”