NON-INVASIVE ASSESSMENT OF PEDIATRIC GLOMERULONEPHRITIS USING RENAL TRACTOGRAPHY: INSIGHTS FROM PRE- AND POST-TREATMENT COMPARISONS

Childhood-onset glomerulonephritis is a major cause of end-stage renal disease in adolescence and young adulthood. Histopathological diagnosis by renal biopsy remains indispensable for therapeutic decision-making; repeated biopsies would ideally be performed during follow-up to monitor disease course. However, the procedure is invasive and carries a non-negligible risk of complications such as renal hemorrhage or hematoma, with an incidence of approximately 1% according to the registry of the Japanese Society of Nephrology. In pediatric patients, the burden is even greater, as cooperation with breath-holding is often difficult and sedation or general anesthesia is frequently required. 

Thus, there is a strong clinical need for a non-invasive imaging modality that can detect renal tissue injury and monitor treatment response with less risk and burden. Diffusion tensor imaging (DTI) has been increasingly applied to renal diseases, and tractography (TG), which has been widely used in neurosurgical navigation to visualize white matter tracts, has the potential to depict renal tubular structures. Animal studies have demonstrated that renal TG can delineate tubular orientation, suggesting that it may serve as a surrogate marker of microstructural integrity. Nevertheless, clinical reports evaluating chronic glomerulonephritis using TG are extremely limited. Moreover, unlike renal biopsy, TG is non-invasive and can be repeated multiple times without concern for procedural risk, which is a particular advantage in pediatric practice. 

The present study aimed to generate renal TG in pediatric patients with glomerulonephritis and to compare tractographic indices before and after treatment in order to explore its potential utility as a non-invasive biomarker.

We enrolled nine pediatric patients with biopsy-proven glomerulonephritis, all of whom underwent MRI without sedation: six with IgA nephropathy and three with Henoch–Schönlein purpura nephritis. The age at biopsy ranged from 9 to 19 years, and all the patients were diagnosed in childhood through school urinary screening. Written informed consent was obtained from all patients prior to imaging examinations. Renal DTI was performed twice, one week after biopsy (prior to initiation of treatment) and again 1–18 months after treatment had begun. TG was reconstructed using Diffusion ToolKit (version 0.6.4.1; available at http://trackvis.org/dtk) and visualized with TrackVis. From the reconstructed tractograms, we calculated the following indices: total fiber count (FiberCount), weighted mean fiber length (WeightedMean), median fiber length (Median), and the 90th percentile of fiber length distribution (P90). Pre- and post-treatment values were compared using the Wilcoxon signed-rank test. The tractographic indices derived from these analyses were then compared between pre- and post-treatment scans to evaluate treatment-related changes in renal microstructure.

As summarized in Table 1, FiberCount significantly increased after treatment (median difference +208 fibers, p = 0.0039). All patients demonstrated an increase in the number of reconstructed fibers, suggesting improved depiction of medullary-oriented tracts following therapy. WeightedMean fiber length showed a non-significant upward trend (median difference +0.38, p = 0.1289). Median fiber length did not show a significant change (median difference –0.65, p = 0.4258). P90 also did not differ significantly (median difference –0.60, p = 0.1641), and in some cases exhibited a slight decrease. Representative tractograms illustrated that post-treatment images displayed more continuous and radially oriented medullary fibers compared with baseline, supporting the quantitative findings.

Table 1. Changes in tractography indices before and after treatment.

Values are presented as median [Q1–Q3]. Median differences were calculated using the Wilcoxon matched-pairs signed rank test, with p < 0.05 considered statistically significant. Interpretation of statistical outcomes is summarized in the rightmost column for clarity.

This exploratory study demonstrated that TG can visualize treatment-related changes in pediatric glomerulonephritis. The significant increase in FiberCount after therapy suggests that TG may reflect partial recovery of tubular orientation and microstructural integrity. In contrast, fiber length indices did not show consistent changes, which may be attributable to the sensitivity of tract length to motion artifacts, parameter settings, and the inherent limitations of renal TG. The clinical implication of these findings is that TG provides an intuitive and visually accessible representation of renal microstructural changes, which may be particularly valuable in pediatric practice where patient and family communication is essential. Importantly, TG could also be applied to adult renal diseases, including the evaluation of allograft rejection and nephrotoxicity related to immunosuppressive therapy. Although the present study is limited by the small sample size and exploratory design, it highlights the potential of TG as a non-invasive adjunct to renal biopsy. Future studies with larger cohorts, standardized acquisition and reconstruction protocols, and integration with conventional DTI metrics such as fractional anisotropy and mean diffusivity are warranted to establish TG as a clinically applicable biomarker for disease monitoring and treatment response in both pediatric and adult glomerulonephritis.