Delta corticomedullary apparent diffusion coefficient on MRI as a biomarker for prognosis in IgA nephropathy

Objectives: To explore the association of the cortico-medullary difference in apparent diffusion coefficient (ΔADC) with clinicopathological parameters of disease activity at the time of biopsy, and with the prognositic risk stratification in IgA nephropathy (IgAN) patients.

Methods: We included 112 patients with biopsy-proven IgAN who measured ΔADC. Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of the biopsy. Clinicopathological characteristics were compared according to different ΔADC levels. The effect of ΔADC on eGFR and kidney fibrosis was explored using multivariate regression and ROC analysis. An individual's 5-year risk probability of progressing to ESKD or decreasing of eGFR > 50% was calculated by the guidelines-recommended international risk-prediction tool in IgAN. The effect of ΔADC on prognostic risk stratification was assessed. Net reclassification improvement (NRI) was used to evaluate the model performance.

Results: The average ΔADC was 168.89 ± 85.1 x10^-6 mm²/s. ΔADC levels decreased significantly with increasing chronic kidney disease (CKD) stages (p = 0.0038). Spearman correlation analysis revealed that ΔADC was positively correlated with eGFR, hemoglobin, serum albumin, while negatively correlated with levels of serum creatine (Scr), blood urea nitrogen (BUN), T score of Oxford classification and Lee grades (p < 0.05). Moreover, we showed that ΔADC was independently associated with eGFR (β = 0.04, 95% CI = [0.003, 0.077], p = 0.033) demonstrated by a backward stepwise multivariate linear regression analysis. Besides, ΔADC, a combination of ΔADC and eGFR showed an AUC of 0.776 (60% sensitivity and 85.3% specificity) and an AUC of 0.875 (100% sensitivity and 69.6% specificity) respectively for evaluating kidney interstitial fibrosis (IF) severity. Furthermore, ΔADC showed an AUC of 0.792 (95% CI 0.677-0.906) for differentiating higher progression risk categories from lower categories (specificity = 91.6%, sensitivity = 58.8%). The low-ΔADC group (≤ median value 167.1 × 10^-6 mm²/s) was associated with 7.509-fold higher likelihood of higher progression risk compared to the high-ΔADC group (>167.1 × 10^-6 mm²/s) in a fully-adjusted model. And reclassification analyses confirmed that the final adjusted model improved NRI.

Conclusions: ΔADC was significantly associated with kidney function and enabled a reliable evaluation of kidney IF severity in IgAN patients. Low ΔADC can predict a high 5-year kidney progression risk in IgAN, independent of important clinical factors. Moreover, the predictive ability to identify patients at high risk of severe kidney fibrosis and adverse progression estimates with satisfactory accuracy, facilitating ΔADC a promising and noninvasive tool in complementarily evaluating disease activity and the prognostic risk stratification in patients with IgAN.