Persistent Isolated C3 Hypocomplementemia as a Strong Predictor of End-Stage Kidney Disease in Lupus Nephritis
Giovanni Maria Rossi, Umberto Maggiore, Francesco Peyronel, Paride Fenaroli, Marco Delsante, Giuseppe Daniele Benigno, Davide Gianfreda, Maria Letizia Urban, Zerai Manna, Lois J. Arend, Serena M. Bagnasco, Augusto Vaglio, Enrico Fiaccadori, Avi Z. Rosenberg, Sarfaraz Hasni, Lucio Manenti
Abstract
Introduction: Proliferative lupus nephritis (LN) progresses to end-stage kidney disease (ESKD) in roughly 10% of the cases despite treatment. Other than achieving <0.8 g/24h proteinuria at 12 months after treatment, early biomarkers predicting ESKD or death are lacking. Recent studies encompassing not only LN have highlighted the central role of the alternative complement pathway (ACP), with or without histological evidence of thrombotic microangiopathy (TMA), as a key promotor of renal death. Methods: We assessed whether persistent isolated C3 hypocomplementemia (PI-LowC3), that is not accompanied by C4 hypocomplementemia, 6 months after kidney biopsy, is associated with an increased risk of death or ESKD in proliferative LN. Results: = 0.012). Conclusion: Our findings support the use of PI-LowC3 as a low-cost readily available biomarker, allowing clinicians to modify treatment strategies early in the course of disease and offering a rationale for complement blockade trials in this particularly at-risk subgroup of LN patients.