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Introduction: Anti-U1 ribonucleoprotein (U1RNP) antibodies are characteristic of mixed connective tissue disease (MCTD) but are also detected in other connective tissue diseases, particularly systemic lupus erythematosus (SLE). Data on kidney manifestations in U1RNP-positive patients across CTD phenotypes remain limited. We aimed to characterise renal involvement using a serology-driven stratification approach.

Methods: Retrospective single-centre cohort of 152 U1RNP-positive patients (University Hospital of Cologne, 2010–2023). Patients were stratified into four serological groups: isolated U1RNP (Sm−/dsDNA−, n=70; G1), U1RNP+Sm (Sm+/dsDNA−, n=15; G2), U1RNP+dsDNA (Sm−/dsDNA+, n=45; G3), and U1RNP+Sm+dsDNA (Sm+/dsDNA+, n=22; G4). Renal involvement was defined as microalbuminuria without another identifiable cause (mild) or macroalbuminuria/histologically confirmed nephritis (moderate to severe). Comparisons used Kruskal–Wallis, χ², Fisher's exact tests with Bonferroni correction (α=0.05, SPSS v31.0).

Results: The cohort was 85.5% female, mean age at diagnosis of 33 years. Serological grouping strongly correlated with clinical phenotype: isolated U1RNP was associated with MCTD/UCTD (88.5%), while U1RNP+Sm+dsDNA comprised mainly SLE (86.4%). Severe renal manifestations occurred in 3.0% (G1), 40.0% (G2), 25.0% (G3), and 63.6% (G4) (p<0.001). Post-hoc comparisons confirmed significant differences between G1 vs. G2 (p=0.002), G1 vs. G3 (p=0.007), G1 vs. G4 (p<0.001), and G3 vs. G4 (p=0.014), indicating that anti-Sm and anti-dsDNA co-positivity independently contribute to renal risk. CKD prevalence increased from 13.0% (G1) to 63.6% (G4, p<0.001), with five patients requiring dialysis. Among 25 biopsied patients, membranous LN (class V) was the most frequent finding (13 cases), often combined with other classes. Proliferative LN occurred exclusively in anti-dsDNA-positive patients, while the U1RNP+Sm+dsDNA group showed the broadest LN spectrum. Neither anti-U1RNP subtype (RNP-70, RNP-A, RNP-C) nor antibody titres (ANA, anti-dsDNA) were associated with renal involvement.

Conclusion: In U1RNP-positive patients, renal risk increases with serological complexity. Co-positivity with anti-Sm and/or anti-dsDNA is key determinant of renal manifestations, whereas isolated U1RNP positivity is rarely nephritogenic. These findings suggest accompanying autoantibody constellations rather than U1RNP alone drive renal disease. A serology-based approach may improve renal risk identification in this heterogeneous population.

Literatur

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