Abstract: Background Mitochondrial dysfunction in tubular epithelial cells increases reactive oxygen species (ROS), promoting inflammation and Chronic Kidney Disease (CKD) progression. Mitophagy, the selective removal of damaged mitochondria, may regulate oxidative stress and maintain cellular function. Hypothesis Mitophagy activity is increased in kidneys of cats with progressive CKD. Animals Snap-frozen kidney tissue from cats (> 9 years), with normal kidney function and with stable and progressive CKD (n = 7/group) obtained post-mortem. Methods Mitophagy marker phosphoserine 65 (pSer65) was measured spectrophotometrically. For mitochondrial integrity, Optic Atrophy-1 (OPA-1) levels were semi-quantified by Western blotting and data were normalized to CD10. Data were analyzed using Kruskal–Wallis tests with Dunn correction. Results pSer65 was higher in progressive CKD (1.31 [0.69–2.45]) than controls (0.24 [0.20–0.28], p = 0.01) and trended higher than stable CKD (0.37 [0.30–0.58], p = 0.15). Total OPA-1 was elevated in progressive CKD (5.16 [2.94–15.98]) versus controls (1.08 [0.65–1.42], p = 0.008). Long-OPA1 forms were lower in progressive CKD (0.63 [0.43–1.05]) than controls (1.18 [1.14–1.64], p = 0.02) and trended lower than stable CKD (0.98 [0.88–1.32], p = 0.22). S-OPA1/L-OPA1 ratios were variable, with no significant differences between groups (progressive CKD 0.97 [0.55–4.55], stable CKD 0.53 [0.26–1.86], controls 0.21 [0.15–0.25]). Conclusions and Clinical Importance Progressive CKD is associated with compensatory increases in mitochondrial integrity and mitophagy. These mitochondrial quality-control mechanisms may inform the development of targeted CKD therapies.
