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Background: Children with chronic kidney disease (CKD) usually present with disease impact on growth besides cardiovascular problems that not only impact the patient's health during childhood but also affect their adult life. We aimed to identify the diagnostic role of diffusion tensor imaging (DTI) in CKD in pediatric using its metrics: apparent diffusion coefficient (ADC) and fraction anisotropy (FA). Results: This prospective study was performed on thirty-five CKD patients (16 girls, 19 boys; mean age 12.3 ± 2.6 years) and 19 sex- and age-matched controls. Both groups underwent renal DTI and renal function tests. Based on renal biopsy, patients with CKD were further categorized into sclerotic CKD (n = 25) and non-sclerotic CKD (n = 10). Mean FA renal medulla/cortex in CKD (0.18 ± 0.18 and 0.20 ± 0.17) was lower significantly (p = 0.001) than volunteers' (0.31 ± 0.19, 0.27 ± 0.18). The cutoff FA of renal medulla/cortex used for CKD diagnosis was 0.22 and 0.23 with AUC of 0.828, 0.838 and accuracy of 80.8%, 82.8%. Mean of renal medulla/cortex ADC in CKD (2.13 ± 0.23 and 1.93 ± 0.22 × 10−3 mm2/s) was higher significantly (p = 0.001) than that of volunteers' (1.67 ± 0.15 and 1.64 ± 0.133 × 10−3 mm2/s. ADC cutoff value of renal medulla/cortex used for CKD diagnosis was 1.86 and 1.74 × 10−3 mm2/s with AUC of 0.827, 0.82, 0.827, and 0.911, and accuracy of 80.6%, 79.6%, 82.8%, and 84.2%. Renal medulla/cortex FA in sclerotic CKD was significantly different (p = 0.001) from non-sclerotic CKD (0.25 ± 0.07 and 0.26 ± 0.08). Cortical and medullary FA in CKD patients correlated with e-GFR (r = 0.363, r = 0.317) and serum creatinine (r = − 0.467, r = − 0.383). Conclusions: Renal cortical/medullary FA can assist in diagnosing pediatric CKD, predict sclerotic CKD, and correlate with some serum biomarkers. [ABSTRACT FROM AUTHOR]