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Oxidative stress and macrophage infiltration in IgA nephropathy

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Abstract

Background

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN).

Methods

A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining.

Results

Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7–7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021].

Conclusions

An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

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Authors and Affiliations

  1. Division of Nephrology, Saint Louis University School of Medicine, 3660 Vista Ave, Saint Louis, MO, USA

    Yasar Caliskan & Krista L. Lentine

  2. Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Yasar Caliskan, Erol Demir, Safak Mirioglu, Ahmet Burak Dirim, Ayse Serra Artan, Ozgur Akin Oto, Aydin Turkmen & Halil Yazici

  3. Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Ecem Karatay & Yasemin Ozluk

  4. Division of Nephrology, Bezmialem Vakif University School of Medicine, Istanbul, Turkey

    Safak Mirioglu

  5. Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Sebahat Usta Akgul & Fatma Savran Oguz

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  1. Yasar Caliskan
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  2. Erol Demir
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  3. Ecem Karatay
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  4. Yasemin Ozluk
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Contributions

YC, ED, SM and HY participated in study design, acquisition of data and regulatory approvals, data analysis, and writing of the paper. ABD, AT and KLL participated in study design, interpretation, and writing of the paper. YS and EK assessed all biopsy samples and participated in interpretation and writing of the paper. SUA and FSO measured serum levels of Gd-IgA1 and AOPP and also participated in interpretation and writing of the paper. ED, OAO and ASA reviewed the patient charts and participated in data interpretation and writing of the paper.

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Correspondence to Yasar Caliskan.

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The research was approved by the local ethical committee of Istanbul University.

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Caliskan, Y., Demir, E., Karatay, E. et al. Oxidative stress and macrophage infiltration in IgA nephropathy. J Nephrol 35, 1101–1111 (2022). https://doi.org/10.1007/s40620-021-01196-7

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