Mitochondria-associated endoplasmic reticulum membranes in canine and feline diabetic kidney disease: mechanistic links and nutritional implications

Diabetic kidney disease in dogs and cats is clinically relevant but mechanistically underdefined, and the dietary management of diabetic pets is still dominated by empirical control of glycemia, body weight, and renal nutrient load. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic contact domains that coordinate calcium transfer, lipid exchange, ER stress, mitochondrial quality control, inflammatory signaling, and cell death. This review first summarizes the veterinary clinical context of canine and feline diabetic kidney disease, including proteinuria, microalbuminuria, hypertension, chronic kidney disease, and species-specific differences in diabetes pathophysiology. It then integrates MAM biology into core renal injury modules involving structural tethering proteins, the IP3R-GRP75-VDAC-MCU/MICU1 calcium axis, lipid metabolic enzymes, PERK/GRP78-mediated ER stress, mPTP opening, mitophagy, and inflammatory amplification. Because direct MAM evidence in diabetic dogs and cats remains limited, the MAM-related pathways discussed here are presented as hypotheses inferred from rodent DKD models, human cell lines, and broader metabolic-disease studies rather than as confirmed mechanisms in companion animals. Finally, we discuss how MAM-centered mechanisms may guide the development of functional prescription diets incorporating EPA/DHA, medium-chain triglycerides, L-carnitine, taurine, magnesium, N-acetylcysteine, antioxidants, resveratrol, and selected plant extracts, provided that efficacy and safety are validated using species-specific renal endpoints. This perspective may support a transition from empirical formulation to mechanism-informed precision nutrition for diabetic dogs and cats.