Hong Liu,* Guijing Tang,* Danyan Yu, Peng Gu, Xingyu Zhu, Anni Wang, Yuan Yuan, Xue Jiang

Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xue Jiang, Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453, Stadium Road, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email monica_jiang@163.com

Purpose: Inflammation and immune factors are closely related to the development of IgA nephropathy (IgAN), and the aggregate index of systemic inflammation (AISI) has been identified as a prognostic indicator for various diseases lately. We aimed to evaluate its predictive value in IgAN.
Patients and Methods: This retrospective single-center study included 1792 biopsy-confirmed IgAN patients from October 2019 to September 2023 with> 12-month follow-up. The optimal cut-off value of AISI for renal poor outcome was identified by receiver operating characteristic curves (ROC). Cox regression analyses, Kaplan-Meier curves and restricted cubic splines were performed to determine the relationship between AISI and IgAN prognosis. The predictive value of AISI on IgAN prognosis was conducted by the area under the receiver operating characteristic curve (AUC).
Results: A total of 1792 IgAN patients were included in the study and were divided into three groups (tertial 1-3) according to the baseline AISI. The higher AISI groups had worse clinicopathological features and renal survival showed by Kaplan-Meier analysis (Log-Rank=17.38, P< 0.001). Multivariate Cox regression identified elevated AISI as an independent risk factor for renal prognosis in IgAN (adjusted HR:2.359,95% CI:1.365– 4.078, P=0.002). Subgroup analysis highlighted significance in male, uric acid> 420μmol/L, 24h proteinuria> 3.5g, eGFR> 30mL/min/1.73m², and the Oxford classification of renal pathology (MEST-C) T0-T1. The best cut-off AISI for renal survival was 198.78, sensitivity 70.0%, and specificity 51.4% (AUC:0.626). Patients were divided into a low AISI group (AISI≤ 198.78, n=894) and a high AISI group (AISI> 198.78, n=898) according to AISI cut-off value and propensity matched. Multivariate Cox regression analysis revealed that a higher AISI was significantly associated with a poorer renal outcome of IgAN patients (HR:1.568,95% CI:1.007– 2.442, P=0.046). Multivariate adjusted restricted cubic splines demonstrated a linear correlation between AISI and a poor renal prognosis (P for overall=0.0135, P for nonlinearity=0.773).
Conclusion: AISI is a novel independent predictor of renal progression in IgAN patients.

Keywords: the aggregate index of systemic inflammation, IgA nephropathy, renal survival, prognosis