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Mesangial IgM deposition predicts renal outcome in patients with IgA nephropathy: a multicenter, observational study

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Abstract

Mesangial IgM deposition is found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients. A total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1:1 propensity score matching (PSM) method identifying age, gender and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN. During a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores, respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end-stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan–Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11–2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02–2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19–2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01–3.24; P = 0.04). Mesangial IgM deposition is associated with histological activity, clinical severity and renal outcome and is an independent risk factor for poor renal prognosis in IgAN.

Trial registration

TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

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Funding

Sincere thanks should be given to all of our colleagues at West China Hospital of Sichuan University, especially Division of Nephrology. This study was partly supported by the Science and Technology Planning Project of Sichuan Province (No. 2019YFS0280).

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Li Tan, Yi Tang, Gai-Qin Pei, Jia-Xing Tan & Wei Qin

  2. Division of Nephrology, Department of Medicine, Affiliated Hospital of Zunyi Medical University, Medical University, Zunyi, Guizhou, China

    Zheng-Xia Zhong

  3. Division of Nephrology, Zigong Third People’s Hospital, Zigong, Sichuan, China

    Ling Zhou

  4. Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Ya Ma

  5. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China

    Dong-Guang Wang

  6. West China School of Medicine, Sichuan University, Chengdu, Sichuan, China

    Li Tan, Gai-Qin Pei, Zheng-Xia Zhong, Jia-Xing Tan, Dong-Guang Wang & Ling Zhou

  7. Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    David Sheikh-Hamad

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  1. Li Tan
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Contributions

LT, WQ and YT contributed to conception and design; WQ and YT contributed to administrative support; LT, G-Q P, Z-X Z, J-X T, YM, D-G W and LZ collected and assembled the data; LT contributed to data analysis and interpretation; LT, DSH and WQ contributed to manuscript writing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wei Qin.

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The authors declare no conflict of interest.

Ethical approval

The Ethics Committee of West China Hospital of Sichuan University, Affiliated Hospital of Zunyi Medical University, Zigong Third People’s Hospital and People’s Hospital of Mianzhu City approved this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Tan, L., Tang, Y., Pei, GQ. et al. Mesangial IgM deposition predicts renal outcome in patients with IgA nephropathy: a multicenter, observational study. Clin Exp Med 21, 599–610 (2021). https://doi.org/10.1007/s10238-021-00703-1

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  • DOI: https://doi.org/10.1007/s10238-021-00703-1

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