Savino Sciascia1, Alice Barinotti2, Massimo Radin2, Irene Cecchi1, Elisa Menegatti2, Vittorio Modena2, Daniela Rossi2, Simone Baldovino2, Roberta Fenoglio2 and Dario Roccatello2, 1University of Turin, Torino, Italy, 2University of Turin, Turin, Italy
Background/Purpose: Lupus Nephritis (LN) is a major cause of mortality/morbidity in patients affected by Systemic Lupus Erythematosus (SLE). Reliable prognostic markers, especially related to the degree of interstitial fibrosis, are still lacking and renal biopsy still represents the gold standard. Recent data suggests a role of Dickkopf homolog 3 (DKK3) as a marker of tissue fibrosis in different diseases, however its role in autoimmune diseases still needs to be elucidated.
The aim of this work was to investigate DKK3 serum levels in SLE patients with and without LN, assessing its changes in relation to kidney function, flares and interstitial renal fibrosis, as well as its association with the IFN signature.
Methods: 132 SLE patients, 57 of whom diagnosed with LN, were included in this study, as well as 50 healthy donors. DKK3 and Myxovirus resistance protein 1 (MxA) were measured in serum samples, using enzyme-linked immunosorbent assays. Biopsies were evaluated for glomerular involvement, interstitial renal fibrosis and tubular atrophy according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and the revised 2018 version. Patients were followed-up for at least 36 months.
Results: DKK3 serum levels were significantly higher in patients with biopsy-proven LN when compared to those without (median [min-max]: 215ng/ml [81-341] vs 21.1ng/ml [1-69], p< 0.01). When focusing on patients with LN, DKK3 levels resulted to be associated with the presence of chronic kidney disease (OR: 4.31[C.I. 2.01-6.61] per DKK3 doubling, p< 0.01), higher chronicity index at biopsy (OR: 1.75 [C.I. 1.59-2.13] per DKK3 doubling, p< 0.01) and flares rate (OR: 1.45[C.I. 1.1-5.71] per DKK3 doubling, p< 0.044). DKK3 levels correlated with the IFN signature as expressed by MxA (correlation coefficient: 0.71, p< 0.037).
Conclusion: While kidney biopsy remains the gold standard for diagnostic and prognostic assessment in LN, DKK3 could represent an additional useful prognostic tool to monitor SLE patients and eventually to guide therapeutic choices.
Disclosures: S. Sciascia, None; A. Barinotti, None; M. Radin, None; I. Cecchi, None; E. Menegatti, None; V. Modena, None; D. Rossi, None; S. Baldovino, None; R. Fenoglio, None; D. Roccatello, None.
