Delta Corticomedullary Apparent Diffusion Coefficient Aids IgAN Risk Stratification

The corticomedullary difference in apparent diffusion coefficient (ΔADC) may be a valuable noninvasive tool for complementarily evaluating disease activity and stratifying prognostic risk in patients with IgA nephropathy (IgAN), according to findings from a recent study.1

Results provide evidence supporting the role of ΔADC in assessing the clinical, pathological, and prognostic risk stratification of patients with IgAN. In addition to being significantly associated with eGFR, ΔADC enabled a reliable evaluation of kidney interstitial fibrosis (IF) severity and facilitated accurate 5-year kidney progression risk prediction.1

IgAN is a leading cause of glomerulonephritis and renal failure, with an estimated 20% to 50% of affected patients developing end-stage renal disease within 20 years of diagnosis. The clinical course of IgAN varies from patient to patient, underscoring the importance of prompt diagnosis, accurate prognostic risk stratification, and appropriate disease management.2

“Given the high risk of progression and limited treatment options, precise risk stratification is essential for guiding treatment and resource allocation, which may be helpful for the guidance of making clinical decisions and reasonably allocating medical resources,” Yanggang Yuan, MD, a professor in the department of nephrology at Nanjing Medical University in China, and colleagues wrote.1

To explore the association between ΔADC and clinicopathological parameters of disease activity at the time of biopsy as well as the prognostic risk stratification of patients with IgAN, investigators conducted a cross-sectional study of 127 patients 18-65 years of age who were diagnosed with IgAN by renal biopsy in a single center between April 2020 and April 2022.1

All patients underwent non-contrast-enhanced magnetic resonance imaging (MRI) of the kidneys, including T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), and axial DWI, either prior to or within 1 week of renal biopsy. Clinicopathological characteristics were compared according to different ΔADC levels; an individual’s 5-year risk probability of progressing to ESKD or experiencing a decrease in eGFR by > 50% was calculated by the guideline-recommended international risk-prediction tool in IgAN; and the effect of ΔADC on prognostic risk stratification was assessed.1

Among the cohort, the mean age was 40.04 ± 13.69 years and the median kidney disease duration was 8 (IQR, 1 to 24) months. At the time of biopsy, the median urinary protein was 0.6 g/d (IQR, 0.3 to 1.42) and eGFR was 100 mL/min/1.73 m2 (IQR, 75 to 112.25).1

The average ΔADC was 168.89 ± 85.1 x10−6 mm2/s. Investigators divided patients into a high-ΔADC group, defined as > 167.1 × 10−6 mm2/s (n = 56), and a low-ΔADC group, defined as ≤167.1 × 10−6 mm2/s (n = 56).1

Of note, more patients had predicted 5-year kidney progression risks > 20% in the low-ΔADC group compared with the high-ΔADC group (23% vs 7%; P = .035). Investigators pointed out ΔADC levels decreased significantly with increasing chronic kidney disease stages (P = .0038).1

Spearman correlation analysis showed ΔADC was positively correlated with the following variables:

• eGFR (r = .230; P = .015)
• 24h urinary calcium (r = .310; P = .001)
• Urine specific gravity (r = .206; P = .029)
• Hemoglobin (r = .247; P = 0.009)
• Serum albumin (r = .247; P = .009)

Additionally, ΔADC was negatively correlated with the following variables:

• Levels of Scr (r = −.271; P = .004)
• BUN (r = −.304; P = .001)
• T score of Oxford classification (r = −.276; P = .003)
• Lee grades (r = −.187; P = .048)

Further analysis revealed ΔADC was independently associated with eGFR (β = 0.04; 95% CI, 0.003-0.077; P = .033), as demonstrated by a backward stepwise multivariate linear regression analysis.1

ΔADC showed an AUC of 0.776 for discriminating T1-2 from T0, with a sensitivity of 60% and a specificity of 85.3%. Investigators noted the combination of ΔADC and eGFR showed an AUC of 0.875 with 100% sensitivity and 69.6% specificity to discriminate moderate-to-severe IF from mild IF.1

Additional ROC analysis showed ΔADC had an AUC of 0.792 for differentiating higher progression risk categories from lower categories, with a specificity of 91.6% and a sensitivity of 58.8%.1

When patients were stratified by median values of ΔADC, the low-ΔADC group had 3.930 times the risk for higher progression risk categories (95% CI, 1.285-14.755; P = .024) compared with the high-ΔADC group in unadjusted models. After adjusting for age, gender, and duration of kidney disease, the association was still significant (OR, 3.417; 95% CI, 1.088-13.062; P = .047). Investigators noted this increased risk remained in the low-ΔADC group, even after further adjustment for MAP, 24h urinary protein, use of RAASi, and use of immunosuppressive therapy (OR, 7.509; 95% CI, 1.585-48.460; P = .018).1

Investigators acknowledged multiple limitations to these findings, including the monocentric study design; the small number of participants; the use of a risk-prediction tool rather than real-world observation of kidney endpoints; and the lack of evaluation of other kidney functional MRI parameters beyond ΔADC.1

“Our findings supply evidence for the role of ΔADC in assessing the clinical, pathological, and prognostic risk stratification of IgAN patients,” investigators concluded.1

References

1. Wang Z, Jiang L, Lu F, et al. Delta corticomedullary apparent diffusion coefficient on MRI as a biomarker for prognosis in IgA nephropathy. Renal Failure. https://doi.org/10.1080/0886022X.2024.2441394
2. Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. April 22, 2024. Accessed December 18, 2024. https://www.ncbi.nlm.nih.gov/books/NBK538214/