The predictive value and response to immunosuppressive therapy of IgA nephropathy patients with crescents in a large retrospective Chinese cohort

Background The prognostic value and response to immunosuppressive therapy (IST) of patients with crescents in the different backgrounds of pathological presentations in immunoglobulin A nephropathy (IgAN) is unclear. Methods A total of 1262 IgAN patients were enrolled. Crescents (C, 0/1/2), fibrinoid necrosis (FN, 0/1) and endocapillary hypercellularity (E, 0/1) were integrated into different degrees of glomerular activity (0-4 points): mild (0), moderate (1-2) and severe (& GE;3). The effect of IST on patients with different glomerular activity scores and chronic tubular and interstitial lesions (T, 0/1/2) were analysed using Cox regression analysis. The kidney outcome was defined as an estimated glomerular filtration rate decrease & GE;30% or end-stage kidney disease. Results C2 was an independent risk factor for kidney outcomes {overall cohort: hazard ratio [HR] 1.85 [95% confidence interval (CI) 1.03-3.31], P = .040; T0 patients: HR 6.52 [95% CI 2.92-14.54], P < .001; reference to C0} in those without IST, while the HR decreased to 0.83 (95% CI 0.54-1.27; P = .396) in the overall cohort and 2.39 (95% CI 1.00-5.67; P = .049) in T0 patients with IST. For patients with severe glomerular activity, IST decreased the risk of kidney outcomes by 70% in the overall cohort [HR 0.30 (95% CI 0.12-0.74), P = .009; reference to those without IST] and 86% in T0 patients [HR 0.14 (95% CI 0.04-0.54), P = 0.005; reference to those without IST]. Conclusions IST could reduce the risk for kidney outcomes in IgAN patients with C2 and T0 lesions together, as well as in those with crescents and at least one other active lesion, including FN and E1 lesions. Lay Summary The evidence to make immunosuppressive therapy decisions according to the presence and number of crescents at the time of kidney biopsy is insufficient in immunoglobulin A nephropathy (IgAN). In the present study, crescents (C, 0/1/2), fibrinoid necrosis (FN, 0/1) and endocapillary hypercellularity (E, 0/1) were integrated into different degrees of glomerular activity (0-4 points): mild (0), moderate (1-2) and severe (& GE;3). The effect of immunosuppressive therapy on patients with different degrees of glomerular activity and chronic tubular and interstitial lesions (T, 0/1/2) was analysed. Finally, our study suggested that immunosuppressive therapy could reduce the risk for poor kidney outcomes in IgAN patients with crescents, especially when these patients presented with at least one other active lesion, including fibrinoid necrosis and endocapillary hypercellularity lesions, or mild chronic tubular and interstitial lesions.