Zonulin, as a marker of intestinal permeability, is elevated in IgA nephropathy and IgA vasculitis with nephritis

Qianqian Li; Xiaohan Yuan; Sufang Shi; Lijun Liu; Jicheng Lv; Li Zhu; Hong Zhang

doi:10.1093/ckj/sfac214

Zonulin, as a marker of intestinal permeability, is elevated in IgA nephropathy and IgA vasculitis with nephritis

Clin Kidney J. 2022 Sep 20;16(1):184-191. doi: 10.1093/ckj/sfac214. eCollection 2023 Jan.

Authors

Qianqian Li¹, Xiaohan Yuan¹, Sufang Shi¹, Lijun Liu¹, Jicheng Lv¹, Li Zhu¹, Hong Zhang¹

Affiliation

¹ Renal Division, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China; Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.

Abstract

Background: Immunoglobulin A nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are considered related diseases and share some similar clinicopathologic phenotypes. Elevated circulating galactose-deficient IgA1 (Gd-IgA1)-containing immune complexes and mucosal immunity were associated with the pathogenesis of IgAN and IgAV-N. Recently, studies have identified that the zonulin level, as a modulator of intestinal permeability, is significantly elevated in several inflammatory and autoimmune-related diseases. However, whether zonulin also plays a role in IgAN and IgAV-N is not clear.

Methods: A total of 73 IgAV-N patients, 68 IgAN patients and 54 healthy controls were assessed for circulating zonulin and Gd-IgA1 levels by enzyme-linked immunosorbent assay. The diagnostic efficiency of the combination of zonulin with Gd-IgA1 was evaluated by the area under the receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI) analysis.

Results: Compared with healthy controls, we found that both IgAV-N and IgAN patients had elevated zonulin and Gd-IgA1 levels (P < .001). Additionally, patients with IgAV-N presented with even higher circulating zonulin levels than patients with IgAN (P = .020). The addition of zonulin to Gd-IgA1 showed better predictive performance than Gd-IgA1 alone in the diagnosis of both IgAN and IgAV-N, as illustrated by a significantly increased AUC (IgAN: 0.805 versus 0.708, P = .0021; IgAV-N: 0.886 versus 0.673, P < .001) and significant IDI (IgAN: IDI 0.136, P < .001; IgAV-N: IDI 0.281, P < .001).

Conclusion: Elevated circulating zonulin levels were detected in both patients with IgAV-N and those with IgAN. Combined detection of circulating zonulin and Gd-IgA1 is recommended as a noninvasive diagnostic biomarker for IgAV-N and IgAN.

Keywords: Gd-IgA1; IgA nephropathy; IgA vasculitis with nephritis; intestinal permeability; zonulin.