ANTI-NEPHRIN ANTIBODIES IN ADULT CHINESE PATIENTS WITH IGA NEPHROPATHY AND NEPHROTIC-RANGE PROTEINURIA

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ANTI-NEPHRIN ANTIBODIES IN ADULT CHINESE PATIENTS WITH IGA NEPHROPATHY AND NEPHROTIC-RANGE PROTEINURIA

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Co-author 1

Fenglei Si sifenglei2017@163.com Peking university first hospital Renal Division Beijing China *

Co-author 2

Yue Shu yueshu_ys@163.com Peking university first hospital Renal Division Beijing China -

Co-author 3

Chen Tang yu-gi-oh.tc@hotmail.com Peking university first hospital Renal Division Beijing China -

Co-author 4

Jing Huang huangjingxmu@126.com Peking university first hospital Renal Division Beijing China -

Co-author 5

Pei Chen glhrp@163.com Peking university first hospital Renal Division Beijing China -

Co-author 6

Xujie Zhou zhouxujie@bjmu.edu.cn Peking university first hospital Renal Division Beijing China -

Co-author 7

Sufang Shi shisufang0510@163.com Peking university first hospital Renal Division Beijing China -

Co-author 8

Jicheng Lv jichenglv75@gmail.com Peking university first hospital Renal Division Beijing China -

Co-author 9

Hong Zhang hongzh@bjmu.edu.cn Peking university first hospital Renal Division Beijing China -

Co-author 10

Zhao Cui cuizhao_pku@163.com Peking university first hospital Renal Division Beijing China -

Co-author 11

Lijun Liu lijun.liu@aliyun.com Peking university first hospital Renal Division Beijing China -

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Anti-nephrin autoantibodies are established in podocytopathies such as minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS), yet their prevalence and clinical significance in IgA nephropathy (IgAN) remain unclear. We assessed anti-nephrin antibodies in adults with biopsy-proven IgAN presenting with nephrotic-range proteinuria.

Methods

We retrospectively identified adults with IgAN and nephrotic-range proteinuria (≥3.5 g/24 h) at our center. Plasma samples obtained at the time of kidney biopsy were stored at −80 °C until analysis. Anti-nephrin IgG and IgM levels were measured using a standardized ELISA assay. Clinical, pathological (Oxford classification), treatment, and follow-up data were collected. Prespecified subgroup analyses included patients with nephrotic syndrome (NS) and those with coexisting MCD or podocytopathy.

Results

A total of 234 patients were included (NS, n=105; coexisting MCD/podocytopathy, n=17). Overall anti-nephrin seropositivity was 7.7% (IgG 6.0%, IgM 1.7%; no double-positive). Seropositivity rates were higher in NS (14.3%) and in coexisting MCD/podocytopathy (35.3%). Compared with seronegatives, seropositive patients had heavier proteinuria and lower serum albumin, with similar eGFR. On kidney biopsy, they showed milder chronic lesions by the Oxford score (more M0/S0/T0). Seropositive patients more often received glucocorticoids and achieved higher complete remission rates, with fewer renal events during follow-up. Comparisons of clinical characteristics in IgAN patients with nephrotic-range proteinuria between anti-nephrin positive and negative groups. Clinical characteristics of IgAN patients with nephrotic-range proteinuria by anti-nephrin antibody status.

Conclusion

In adult IgAN with nephrotic-range proteinuria, anti-nephrin antibodies are uncommon overall but enriched in cases with coexisting MCD or podocytopathy, identifying a podocytopathy-leaning phenotype characterized by severe proteinuria yet milder chronic histologic injury and higher remission rates. Targeted testing may aid phenotypic stratification and monitoring, warranting prospective validation.

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