Diabetes mellitus is the leading cause of Chronic Kidney Disease, an increasing threat to global health. However, not all diabetic patients develop Diabetic Kidney Disease (DKD) and patients follow individual trajectories. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently shown notable nephroprotective benefits, becoming a first-line therapy in DKD, but the underlying mechanisms inducing individual response are not fully understood. For better patient management and cost effectiveness, early identification of DKD patients who stand to benefit from SGLT2i would be key. Hence, biomarkers with increased specificity and sensitivity to disease progression and response to treatments are urgently needed. Renal multiparametric MRI (mpMRI) shows potential to investigate kidney pathophysiology. Additionally, serum metalloproteinase-10 (MMP-10) and Tissue inhibitor of metalloproteinase (TIMP-1) show potential to investigate SGLT2i effects on MMPs-related pathways. To build on and validate single-centre preliminary findings, it is key to refine and standardise methodologies, identify optimal biomarker combinations, and provide multi-centre evidence. PERSONALISE-DKD addresses these unmet needs with an international, multidisciplinary and intersectoral project that will identify early mechanisms and predictors of nephroprotection by SGLT2i in DKD using MRI biomarkers for personalised medicine. PERSONALISE-DKD aims to: i) investigate SGLT2i nephroprotective mechanisms in DKD rapid and slow progressors, ii) assess SGLT2i effect on renal microstructure and MMPs-related pathways, iii) preclinically identify renal mpMRI biomarkers most sensitive to acute and chronic SGLT2i effects in DKD, iv) identify the optimal biomarker combinations and develop predictive models allowing to monitor disease progression and response to SGLT2i in DKD, v) ensure reflection on ethical, legal and social issues, and promote active involvement of patients, citizens and other stakeholders.