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. 2024 Dec 3;18(1):sfae395.
doi: 10.1093/ckj/sfae395. eCollection 2025 Jan.

Urine complement-related proteins in IgA nephropathy and IgA vasculitis nephritis, possible biomarkers of disease activity

Mazdak Sanaei Nurmi  1   2 , Laura Pérez-Alós  3 , Peter Garred  3   4 , Bengt Fellström  5 , Katja Gabrysch  6 , Sigrid Lundberg  1   2   7
Affiliations

Urine complement-related proteins in IgA nephropathy and IgA vasculitis nephritis, possible biomarkers of disease activity

Mazdak Sanaei Nurmi et al. Clin Kidney J. .

Abstract

Introduction: The activation of the complement system plays an important role in the pathogenesis of IgA nephropathy (IgAN). Our primary aim was to evaluate a range of complement-related proteins, including pentraxin-3 (PTX-3), in blood and urine at diagnosis and their association with disease activity in the kidney biopsy, eGFR, albuminuria, and outcome. Our secondary aim was to compare the same biomarkers between patients with IgAN and IgA vasculitis with renal involvement (IgAVN).

Methods: In a longitudinal Swedish cohort of 96 patients with IgAN (n = 65) or IgAVN (n = 31), with a median follow-up time of 10.8 years, we analysed mainly lectin-pathway-related proteins and PTX-3 in plasma and urine (u) samples stored at the time of kidney biopsy. Outcome was defined by the GFR slope or by the combined outcome of 50% loss of eGFR or end-stage kidney disease (ESKD).

Results: Patients with detectable vs undetectable u-PTX-3 and u-mannose-binding lectin (MBL) more frequently had mesangial hypercellularity, endocapillary proliferation, and crescents in their kidney biopsy. u-C4c levels were higher in patients with advanced tubulointerstitial fibrosis, and u-C4c was also an independent predictor of a more severe eGFR slope. There were no differences in the levels of biomarkers between patients with IgAN and IgAVN.

Conclusion: u-PTX-3 and u-MBL might be biomarkers of an active proliferative stage of the disease, while higher u-C4c levels indicate more chronic lesions in both IgAN and IgAVN. These results must, however, be confirmed in larger and multiethnic cohorts.

Keywords: IgA nephropathy; biomarkers; complement; glomerulonephritis; vasculitis.

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Conflict of interest statement

No disclosures.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Flow diagram of study participants.
Figure 2:
Figure 2:
Scatterplot and correlations between u-MBL levels vs albuminuria among patients with detectable u-MBL.
Figure 3:
Figure 3:
Scatterplot and correlations between u-PTX-3 levels and albuminuria in patients with detectable u-PTX-3.
Figure 4:
Figure 4:
Box plots of u-C4c levels in patients with and without ESKD or 50% eGFR loss (combined outcome) during the follow up.
Figure 5:
Figure 5:
Survival plot from a Cox proportional hazard model in patients with high vs low u-C4c levels when adjusted for the calculated IIgAN-PT risk score.
See this image and copyright information in PMC

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