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

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).

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.

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.

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.