Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis

Abstract Background Kidney involvement is frequent in SLE, with proliferative lupus nephritis (LN) forms and nephritic flares being key predictors of poor outcomes. Conflicting results have been reported for anti-C1q antibodies among the serological markers. Our purpose was to assess the value of im...

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Main Authors: Marta Calatroni, Emanuele Conte, Matteo Stella, Federica De Liso, Francesco Reggiani, Gabriella Moroni
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Arthritis Research & Therapy
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Online Access:https://doi.org/10.1186/s13075-025-03536-5
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author Marta Calatroni
Emanuele Conte
Matteo Stella
Federica De Liso
Francesco Reggiani
Gabriella Moroni
author_facet Marta Calatroni
Emanuele Conte
Matteo Stella
Federica De Liso
Francesco Reggiani
Gabriella Moroni
author_sort Marta Calatroni
collection DOAJ
description Abstract Background Kidney involvement is frequent in SLE, with proliferative lupus nephritis (LN) forms and nephritic flares being key predictors of poor outcomes. Conflicting results have been reported for anti-C1q antibodies among the serological markers. Our purpose was to assess the value of immunological tests (C3,C4 complement fractions, anti-DNA and antiC1q antibodies) in predicting histological classes and flares of lupus nephritis (LN). Methods For histological class prediction, we evaluated the immunological tests performed on the day of kidney biopsy by linear and multiple regression analyses. For flare prediction, univariable and multivariable Cox analyses were made at baseline, 6, and 12 months. Results Of 61 participants in the study, 47 had proliferative (III, IV) and 14 non-proliferative LN (II, V) at kidney biopsy. In proliferative LN, anti-DNA (p = 0.0186) and anti-C1q antibodies (Ab) (p = 0.0050) were significantly higher, and serum C3 and C4 lower (p = 0.0026; p = 0.0212) compared to non-proliferative LN. At multiple regression analysis, the best association to differentiate proliferative from non-proliferative LN was the number of urinary erythrocytes (OR 3.2292; CI 1.2585–8.2858; p = 0.0148) and anti-C1qAb (OR 1.0288; CI 1.0016–1.0568; p = 0.0380). Of 53 patients evaluated for flare predictions, followed for 60.69 (37.20-78.704) months, 10 (18.86%) had a renal flare at 28.19 months (24.84–39.38, range:16.3–55.8) from therapy initiation. At univariable analysis, anti-C1qAb (p = 0.0340, p = 0.0005) and no-use hydroxychloroquine (p = 0.0313, p = 0.0276) predicted flares at baseline and six months. Anti-C1qAb (p = 0.0047), non-use hydroxychloroquine (p = 0.0252), anti-C1qAb ≥ 40UA (p = 0.0047), 24/h proteinuria (p = 0.0185), and proteinuria ≥ 0.5 g/day (p = 0.0216) predicted flares at 12 months. At multivariable analysis, anti-C1q > 40UA (OR 9.0721; CI 0.9146–42.9882; p = 0.0057) and non-use of hydroxychloroquine (OR 0.1742 CI 0.0445–0.6823; p = 0.0126) were the independent predictors of renal flares. Conclusion Immunological tests can differentiate proliferative from non-proliferative LN, but anti-C1qAb and urinary erythrocytes had the best predictive power. Only persistent high anti-C1qAb at 1 year and non-use of hydroxychloroquine seem to predict renal flares.
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spelling doaj-art-5d84aa53e59c4b19a7bb21a2d2a4f6112025-08-20T03:07:43ZengBMCArthritis Research & Therapy1478-63622025-03-0127111010.1186/s13075-025-03536-5Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritisMarta Calatroni0Emanuele Conte1Matteo Stella2Federica De Liso3Francesco Reggiani4Gabriella Moroni5Department of Biomedical Sciences, Humanitas UniversityNephrological Unit, Nephrology and Dialysis Division, IRCCS Humanitas Research HospitalNephrological Unit, Nephrology and Dialysis Division, IRCCS Humanitas Research HospitalClinical Pathology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Biomedical Sciences, Humanitas UniversityDepartment of Biomedical Sciences, Humanitas UniversityAbstract Background Kidney involvement is frequent in SLE, with proliferative lupus nephritis (LN) forms and nephritic flares being key predictors of poor outcomes. Conflicting results have been reported for anti-C1q antibodies among the serological markers. Our purpose was to assess the value of immunological tests (C3,C4 complement fractions, anti-DNA and antiC1q antibodies) in predicting histological classes and flares of lupus nephritis (LN). Methods For histological class prediction, we evaluated the immunological tests performed on the day of kidney biopsy by linear and multiple regression analyses. For flare prediction, univariable and multivariable Cox analyses were made at baseline, 6, and 12 months. Results Of 61 participants in the study, 47 had proliferative (III, IV) and 14 non-proliferative LN (II, V) at kidney biopsy. In proliferative LN, anti-DNA (p = 0.0186) and anti-C1q antibodies (Ab) (p = 0.0050) were significantly higher, and serum C3 and C4 lower (p = 0.0026; p = 0.0212) compared to non-proliferative LN. At multiple regression analysis, the best association to differentiate proliferative from non-proliferative LN was the number of urinary erythrocytes (OR 3.2292; CI 1.2585–8.2858; p = 0.0148) and anti-C1qAb (OR 1.0288; CI 1.0016–1.0568; p = 0.0380). Of 53 patients evaluated for flare predictions, followed for 60.69 (37.20-78.704) months, 10 (18.86%) had a renal flare at 28.19 months (24.84–39.38, range:16.3–55.8) from therapy initiation. At univariable analysis, anti-C1qAb (p = 0.0340, p = 0.0005) and no-use hydroxychloroquine (p = 0.0313, p = 0.0276) predicted flares at baseline and six months. Anti-C1qAb (p = 0.0047), non-use hydroxychloroquine (p = 0.0252), anti-C1qAb ≥ 40UA (p = 0.0047), 24/h proteinuria (p = 0.0185), and proteinuria ≥ 0.5 g/day (p = 0.0216) predicted flares at 12 months. At multivariable analysis, anti-C1q > 40UA (OR 9.0721; CI 0.9146–42.9882; p = 0.0057) and non-use of hydroxychloroquine (OR 0.1742 CI 0.0445–0.6823; p = 0.0126) were the independent predictors of renal flares. Conclusion Immunological tests can differentiate proliferative from non-proliferative LN, but anti-C1qAb and urinary erythrocytes had the best predictive power. Only persistent high anti-C1qAb at 1 year and non-use of hydroxychloroquine seem to predict renal flares.https://doi.org/10.1186/s13075-025-03536-5Lupus nephritisProliferative lupus nephritisMembranous lupus nephritisanti-DNA antibodiesanti-C1q antibodiesComplement fractions, renal flares
spellingShingle Marta Calatroni
Emanuele Conte
Matteo Stella
Federica De Liso
Francesco Reggiani
Gabriella Moroni
Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
Arthritis Research & Therapy
Lupus nephritis
Proliferative lupus nephritis
Membranous lupus nephritis
anti-DNA antibodies
anti-C1q antibodies
Complement fractions, renal flares
title Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
title_full Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
title_fullStr Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
title_full_unstemmed Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
title_short Clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
title_sort clinical and immunological biomarkers can identify proliferative changes and predict renal flares in lupus nephritis
topic Lupus nephritis
Proliferative lupus nephritis
Membranous lupus nephritis
anti-DNA antibodies
anti-C1q antibodies
Complement fractions, renal flares
url https://doi.org/10.1186/s13075-025-03536-5
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